Handbook of Active Marine Natural Products: Volume 3 Alkaloids, Part 1 9783110655193, 9783110653267

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Jiaju Zhou Handbook of Active Marine Natural Products

Handbook of Active Marine Natural Products Jiaju Zhou Volume : Terpenoids, Part  ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : Terpenoids, Part  ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : Alkaloids, Part  ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : Polyketides and Steroids ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : Aliphatic Metabolites ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : O-Heterocycles and Aromatics ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Volume : Peptides and Others ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Jiaju Zhou

Handbook of Active Marine Natural Products Volume 3: Alkaloids, Part 1

Author Prof. Jiaju Zhou Chinese Academy of Sciences 1303 Department, 10 Building 31 Zhong Guan Cun Nan Dajie 100081 Beijing China [email protected]

ISBN 978-3-11-065326-7 e-ISBN (PDF) 978-3-11-065519-3 e-ISBN (EPUB) 978-3-11-065327-4 Library of Congress Control Number: 2019941348 Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at http://dnb.dnb.de. © 2019 Walter de Gruyter GmbH, Berlin/Boston Typesetting: Integra Software Services Pvt. Ltd. Printing and binding: CPI books GmbH, Leck Cover image: Science Photo Library/Douwma, Georgette www.degruyter.com

Preface The English edition Handbook of Active Marine Natural Products (HAMNP) with 8 Volumes is a selective version of the Marine Natural Products Dataset. The whole dataset was collected and developed by the Molecular Design Group, Institute of Process Engineering, Chinese Academy of Sciences during 1998–2016. Totally, it covers 19,722 entries of secondary metabolites from marine living things, where 8,350 compound entries have pharmacological activity data. The 8,350 compound entries were arranged into eight volumes to form the set of handbooks as follows: Volume 1: Terpenoids, Part 1 Volume 2: Terpenoids, Part 2 Volume 3: Alkaloids, Part 1 Volume 4: Alkaloids, Part 2 Volume 5: Polyketides and Steroids Volume 6: Aliphatic Metabolites Volume 7: O-Heterocycles and Aromatics Volume 8: Peptides and Others This set of eight HAMNP books gathers the structure, origin, and bioactivity, as well as other relevant information, of 8,350 active marine natural products from 3,025 marine organisms. The HAMNP handbooks represent a largest collection of active secondary metabolites from marine organisms, and all kinds of scientific data have been reorganized as well-formatted data so that the books became helpful to researchers as a convenient reference. The materials covered in these books include those through systematic collection up to 2012, and further accompanied with the latest data published in several core journals until 2016. The work covered in these HAMNP books was accomplished in two phases. The initial phase ranged from 1998 to 2001 and the main phase from 2011 to 2018. In the original version of the dataset, more than 22,000 compounds have been collected, including duplicated compounds from different authors. The comprehensive data compilation process include data specification definition, cross-validation, assessment confirmation, identification of duplicated structures, and merging of relevant information, leading to the final accomplishment of the current 19,722 datasets. In brief, the main compilation process of the HAMNP books is given as follows. First, collect the name list, origin, and structure of chemical compounds from successive annual reviews (see Core References R01 and R02 in Introduction) and literature reviews. Second, double-check the documents to verify and complete other information. Third, confirm the structural information and other types of data using orthogonal information from other sources with cross-validation methods. Fourth, the structures of more than 22,000 compounds are rechecked, and the information is integrated by manual identification and computer programs. Finally, the comprehensive information https://doi.org/10.1515/9783110655193-201

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on the 19,722 compounds constitutes the dataset. Here, 8,350 active sets were picked up from the dataset to form the current HAMNP handbooks. Three problems need to be solved to compile a multidisciplinary reference book. First, every definition and concept should be explicit when expanding knowledge, connotation, and extension included, without any research details. Second, the reliability assessment is essential for all kinds of data, because the devil is in the detail. Third, it is essential to search, identify, and integrate data of duplicated chemical compounds. Fortunately, well-developed software packages can help us automatically identify the majority of duplicated chemical compounds. The remaining issues can be resolved along with manual processing. It is the guiding principle of the author to make the book to be pithy, thorough, precise, and intelligible. In fact, we always view ourselves as HAMNP’s readers, with the exclusive objective to let readers gain the most useful knowledge in the shortest possible time. The core contents and highlights of the HAMNP books are the “three diversities,” that is, the diversity of chemical structures, the diversity of biological resources, and the diversity of pharmacological activities. In terms of chemical structure diversity, we refer to the classification system from references, then further improve and expand it based on the latest research and development to define our classification framework of structures. Once readers browse the contents of the books, the classification system is straightforward. For the diversity of biological resources, it is recommended to refer to Index 3 in each volume – Compound Marine Organism Source Index; and Index 4 in each volume – Compound Marine Source Sampling Geographic Location Index. For the diversity of pharmacological activities, it is recommended to refer to Index 5 in each volume – Compound Pharmacological Activity Index. These HAMNP handbooks are expected to help readers who are engaged in research, in teaching, and in the development of marine natural products. It should also benefit college students, postgraduates, marine resource managers, and those who are interested in the chemistry and pharmacology of marine natural products. We would feel fortunate if it works as expected.

Jiaju Zhou Institute of Process Engineering (IPE), Chinese Academy of Sciences (CAS) February 2019

Contents Preface V About the Author IX Introduction XI How to Use the HAMNP Books XIX List of Abbreviations and Acronyms XXV List of Cancer Cell Codes XXXV 1

Amine Guanidine and Amide Alkaloids 1.1 Amine Alkaloids 1 1.2 Guanidine Alkaloids 18 1.3 Amide Alkaloids 44

1

2

Phenylamine and Phenethylamine Amines 75 2.1 Phenylamine Alkaloids 75 2.2 Simple Tyramine Alkaloids 77 2.3 Halogenated Tyrosinoids 83 2.4 Miscellaneous Phenethylamines 116

3

Pyrrole Indole and Imidazole Alkaloids 123 3.1 Pyrrole Alkaloids 123 3.2 Pyrrolidine Alkaloids 197 3.3 Indole Alkaloids 241 3.4 Bisindole Alkaloids 256 3.5 Carbazole Alkaloids 272 3.6 Indolo[2,3-α]carbazole Alkaloids 275 3.7 β-Carboline Alkaloids 283 3.8 Manzamines 310 3.9 Tryptamine Alkaloids 331 3.10 Chaetocin-like Alkaloids 346 3.11 Indole-Imidazole Alkaloids 354 3.12 Indolactam Alkaloids 363 3.13 Indoloterpenoid Alkaloids 366 3.14 Penitrems 370 3.15 Isoindole Alkaloids 379

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3.16 3.17

Miscellaneous Indole Alkaloids Imidazole Alkaloids 392

383

Index 1 Compound Name and Synonym Index 405 Index 2 Compound Molecular Formula Index 420 Index 3 Compound Organism Source Index 445 Index 4 Compound Sampling Geographic Locality Index 454 Index 5 Compound Pharmacological Activity Index 458

About the Author Prof. Jiaju Zhou was born in October 1939 in Tianjin, China. He graduated from Rare Earth Inorganic Chemistry Specialty, Chemistry Department, Peking University, in 1963 under a six-year program. Before he retired in 2008, Zhou was the leader of Molecule Design Group, IPE, CAS. Zhou’s areas of research include rare earth chemistry, mineral analytical chemistry, chemical industry process simulation (in IPE, CAS and UBC, Canada), design of crystal structural database (in OSRD, NIST, Gaithersburg, MD, USA), scientific database R&D, and computer-aided and artificial intelligence drug design. Zhou developed the first TCM database (TCMDB) with 23,033 entries. Since 2008, he has worked on Marine Natural Products project and has developed the Marine Natural Products Database (MNPDB) with 19,722 entries.

https://doi.org/10.1515/9783110655193-202

Introduction The Handbook of Active Marine Natural Products covers eight volumes. This book is Volume 3: Alkaloids, Part 1, which includes 1,162 active compounds. Format of Compound Entry. A compound entry starts with a title line, which has two items: the compound’s unique code (from 1 to 1,162 for volume 3) and the main name. The following seven items form the title line as a body, and the graphic structure is placed at the end: Title line (code number, main name) A. Synonyms of the compound (if any) B. Structural type C. Formula (relative molecular mass) D. Physicochemical properties E. Marine source(s) F. Pharmacological data (if any) G. Reference(s) Graphic structure Chemical Names and A. Synonyms. Generally, a compound may have one scientific name and several trivial names. In the handbooks, based on original articles, we select one name as the “main name.” The main name appeared at the title line of each compound entry. In most cases, a trivial name was selected as the main name, and in some cases, the main name is a scientific name. Any synonyms, if any, are presented after the title line as an item of the entry body. B. Structural Type. Structural type is the second item, ordered by the contents order. F. Normalization of Pharmacological Data. All of 1,162 MNP components in this book have pharmacological data, which are very valuable. Because different expressions are used for the same kind of data in different articles, we have to define and normalize thousands pharmacological terms, so that the data could be expressed in a unified way, and be easily understood by readers. Stereochemistry in Graphic Structure. We protracted all compound structures down to atomic bond level, including complicated glycosides, with stereochemical information based on the data in the original papers. For example, the structure with full stereochemistry of compound 856 Homofascaplysin A is

N

+

N H HO

O

https://doi.org/10.1515/9783110655193-203

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Let us further explain the data structure of source terms and pharmacological terms.

Source Terms The source data of compound 856 Homofascaplysin A is: Source: Sponge Hyrtios cf. erecta Sponge Fascaplysinopsis reticulata Ascidian Didemnum sp. (Pratt Reef, Fiji) The format is as follows (banding the English-type name and the Latin name together): Source: English-type name + Latin name of source 1 (sampling place, sampling season water depth, etc.) English-type name + Latin name of source 2 English-type name + Latin name of source 3

Pharmacological Terms The pharmacological terms in the handbooks are presented in a multilayered structure. In the top layer, there are more than 20 types of most important pharmacological activity terms. They are cytotoxic (in vitro anticancer), antineoplastic (in vivo anticancer), antibacterial, antifungal, antiviral, anti-HIV, anti-inflammatory, antioxidant, antimalarial, NO (nitric oxide) production inhibitors, enzyme inhibitors, cardiovascular activity, smooth muscle relaxant and stimulant, toxin and medium lethal dose (LD50), and so forth. Readers need to be familiar with these Tope lever pharmacological terms (see Table 1). For each term, there is a regulation about how to describe related pharmacological data. The following is an example. Under the subtitle “Pharm:” of compound 856 Homofascaplysin A, a set of multiple biodata is presented as follows: Pharm: Antiplasmodial (Plasmodium falciparum strain K1, IC50 = 14 ng/mL, control chloroquine, IC50 = 54 ng/mL, control artemisinin, IC50 = 1 ng/mL; chloroquinesusceptible Plasmodium falciparum strain NF54, IC50 = 24 ng/mL, chloroquine, IC50 = 4 ng/mL, artemisinin, IC50 = 2 ng/mL) (Kirsch, 2000); cytotoxic (rat skeletal muscle myoblast L-6 cells, MIC = 1.1 μg/mL, mouse peritoneal macrophages, MIC = 30 μg/mL) (Kirsch, 2000);

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Table 1: Twenty-Four Main Pharmacological Terms in Tope Lever. Order in Index 

Pharmacological Terms in Tope Lever

                       

Anti-AD Antibacterial Antifungal Anti-HIV Anti-inflammatory Antileishmanial Antimalarial Antineoplastic (in vivo) Antioxidant Antiplasmodial Antitrypanosomal Antituberculosis Antiviral Cardiovascular activity Cell cycle inhibitor Cell division inhibitor Cell growth inhibitor Cell adhesion inhibitor Cytotoxic (in vitro) Enzyme inhibitors NO production inhibitors Smooth muscle relaxant and stimulant Toxin Medium lethal dose (LD)

antiplasmodial life stage-specific activity (Plasmodium falciparum strain W2-Mef, all live parasites, IC50 = 105 nmol/L, chloroquine, IC50 = 149 nmol/L, artemisinin, IC50 = 6.245 nmol/L; rings stage, IC50 = 0.55 nmol/L, chloroquine, IC50 = 174 nmol/L, artemisinin, IC50 = 5.92 nmol/L; trophozoite stage, IC50 = 252 nmol/L, chloroquine, IC50 = 162 nmol/L, artemisinin, IC50 = 6.46 nmol/L; schizont stage, IC50 = 94 nmol/L, chloroquine, IC50 = 80 nmol/L, artemisinin, IC50 = 5.91 nmol/L); antibacterial (Escherichia coli, 50 μg/9 mm and Bacillus megaterium, 50 μg/ 11 mm) (Kirsch, 2000); p56lck tyrosine kinase inhibitor (reduced to 8% at 0.6 mmol, and to 44% at 0.3 mmol/L) (Kirsch, 2000).

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The format is as follows: Pharm: Term name 1 (formatted detail information) Term name 2 (formatted detail information) Term name 3 (formatted detail information) Term name 4 (formatted detail information) Term name 5 (formatted detail information) Under the term name Cytotoxic, a set of multiple cytotoxic biodata is presented as follows: Cytotoxic rat skeletal muscle myoblast L-6 cells, MIC = 1.1 μg/mL, mouse peritoneal macrophages, MIC = 30 μg/mL. The format is as follows: Term name (in vitro/in vivo, target cancer cell 1, quantitative data, positive control Compound, control’s quantitative data (if any); target cancer cell 2, quantitative data, positive control Compound, control’s quantitative data (if any); brief description of related mechanism if any). In order to standardize abbreviations of cancer cells, such as P388, A549, HT29, MEL28, CCRF-CEM, DLD-1, we defined and used 438 cancer cell codes (CCC) in the handbooks. For explanations of these codes, please see “List of Cancer Cell Codes.” By means of the formatted and structuralized methods, we have normalized expressions of almost all the pharmacological data discussed in the books. For complete information in volume 3, of all 976 normalized pharmacological activity terms, please see “Index 5 Compound Pharmacological Activity Index.” In summary, these handbooks with eight volumes provide an integrated collection of 8,350 marine natural products’ chemical components isolated from 3,025 marine organisms and a large amount of pharmacological activity data of these components. It might be used not only as a handbook to look for structures and bioactivities of marine natural products and marine organisms source information, but also as a fundamental platform for studying the marine natural products with a systematic and integrative approach.

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Acknowledgments First, as the author of those books, I would like to give my heartfelt thanks to Dr. David Lide and B.J. Lide, who were my directors 30 years ago when I worked in OSRD, NIST (former NBS), USA, in 1985–1986 for nine months. They gave me the rare opportunity to learn how to use a software platform and how to treat a complicated scientific information data system. It was my research experience in NBS that helped me to compile easily the current huge project on Marine Natural Products. At the same time, I also give my sincere thanks to my NBS’s colleagues: Dr. John Rumble, Mrs. Geraldine Dalton, Mrs. Phoebe Fagan, and other OSRD members. Then, I would like to give my genuine thanks to the following two close friends. They gave my MNP project continual concerns and supports for years: Dr. Jun Xu, Professor and Director, Research Center for Drug Discovery, Sun Yet-Sen University, 132 East Circle, University City, Guangzhou 510006, China, and Dr. Leming Shi, Professor and Director, Center for Pharmacogenomics, School of Life Sciences and Shanghai cancer Center, Fudan University, Shanghai 200438, China (lemingshi@ fudan.edu.cn). Third, I like to give my honest thanks to my following group members. For many years, all of them gave various devices to me: 1 Dr. Jing Lei, Associate Professor, Educational Equipment Research and Development Centre, Ministry of Education of the People’s Republic of China, Beijing 100080, China (early research in her doctor thesis) 2 Dr. Bing Liu, Lead Dev Prophix Software Inc. 350 Burnhamthorpe Road West, Suite 1000 Mississauga, Ontario L5B 3J1, Canada (data collection in the early stage) 3 Master Yingxin Qiao, Software Engineer, National Library of China, Beijing 100081, China (data source searching and original paper collection) 4 Dr. Haibo Liu, Associate Professor, The Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 100193, China (special software development for automatic edition) 5 Dr. Tao Peng, Associate Professor, College of Robotics, Beijing Union University, Beijing 1001011, China (special software development for index generation) 6 Dr. Aihua Xie, Associate Professor, School of Pharmacy, Hebei Chinese Medical University, Shijiazhuang, Hebei 050200, China (part of data collection) 7 Dr. Chenzhong Liao, Professor, Dean of Department of Pharmacy, School of Biological and Medical Engineering, Hefei University of Technology, Hefei 230009, China (original paper collection) 8 Dr. Jianfeng Pei, Associate Professor, Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China (data collection in the early stage)

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9

Dr. Xianfeng He, Associate Professor, Scientific Researcher, EMMS Group, State Key Laboratory of Multiphase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China (data collection in the early stage) 10 Madam Guirong Xie, Associate Professor, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China (part of data compilation) 11 Mr. Wucheng Tang, Engineer, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China (part of original paper collection). Finally, I thank my family members. Without their complete and never-ending support, this book would never have been possible.

Core References (Guiding References 5) R01 D. J. Faulkner, Marine Natural Products (review), Nat. Prod. Rep., 1986, 3, 1–33; 1987, 4, 539–576; 1988, 5, 613–663; 1990, 7, 269–309; 1991, 8, 97–147; 1992, 9, 323–364; 1993, 10, 497–539; 1994, 11, 355–394; 1995, 12, 223–269; 1996, 13, 75–125; 1997, 14, 259–302; 1998, 15, 113–158; 1999, 16, 155–198; 2000, 17, 7–55; 2001, 18, 1R–49R; 2002, 19, 1–49 R02 J. W. Blunt, et al, Marine Natural Products (review), Nat. Prod. Rep., 2003, 20, 1–48; 2004, 21, 1–49; 2005, 22, 15–61; 2006, 23, 26–78; 2007, 24, 31–86; 2008, 25, 35–94; 2009, 26, 170–244; 2010, 27, 165–237; 2011, 28, 196–268; 2012, 29, 144–222; 2013, 30, 237–323; 2014, 31, 160–258; 2015, 32, 116–211 R03 J. Buckingham (Executive Editor), Dictionary of Natural Products, Chapman & Hall, London, Vol. 1–Vol. 7 1994; Vol. 8, 1995; Vol. 9, 1996; Vol. 10, 1997; Vol. 11, 1998 R04 CRC Press, Dictionary of Natural Products on DVD, version 20.2, 2012 R05 Jean-Michel Kornprobst, Encyclopedia of Marine Natural Products, Vol. 1–Vol. 3, 2nd Edition, WILEY BLACKWELL, Germany, 2014

(Dictionaries 17) R06 P.M. Kirk, P.F. Cannon, D.W. Minter and J.A. Stalpers, Dictionary of the Fungi, 10th Edition, CABI Europe-UK, 2011 R07 Miaoying Cai, et al., Names of Bacteria, 2nd Edition, Science Press, Beijing, 1996 R08 Rui-Fu Yang et al, Dictionary of Bacterial Names with English Explanation and Chinese Translation, Chemical Industry Press, Beijing, 2011 R09 Zongxun Wang et al. (Institute of Botany, Chinese academy of Sciences), New Edited Plant Names in Latin-Chinese-English, Aerial Industry Press, Beijing, 1996 R10 Zhong-Yan Qi and Xi-Xing Liu, New Names of Invertebrate Animals in Latin-Chinese, Science Press, Beijing, 1999 R11 Ling-Ti Lu and Jia-Ran Zhu, Dictionarium Lantino-Sinicum de Scientia et technologia, The Commercial Press, Beijing, 2017 R12 Ji-Sheng Chen, et al., English-Chinese Dictionary of Life Science, Scientific and technological Literature Press, Beijing, 1992

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R13 P. Singleton and D. Sainsbury (Qing-jun Ma and Cheng-hua Shi et al. translated), Dictionary of Microbiology and Molecular Biology, Chemical Industry Press, Beijing, 2008 R14 Scientific Terms Laboratory of Science Press, English-Chinese Dictionary of Chemistry and Chemical Engineering, 4th Edition, Science Press, Beijing, 2000 R15 Scientific Terms Laboratory of Science Press, English-Chinese Dictionary of Chemistry and Chemical Engineering, 5th Edition, Science Press, Beijing, 2016 R16 Jian Zhuge and Zheng-Xiang Wang, Modern English-Chinese Dictionary of Biotechnology, Science Press, Beijing, 2003 R17 Jing-Ying Tan, English-Chinese Biological Dictionary of Biochemistry and Molecular Biology, 2nd Edition, Science Press, Beijing, 2007 R18 Scientific Terms Laboratory of Science Press, English-Chinese Biological Dictionary, 2nd Edition, Science Press, Beijing, 1997 R19 Scientific Terms Laboratory of Science Press, Chinese-English Biological Dictionary, 2nd Edition, Science Press, Beijing, 1998 R20 Yu Hui, A New Century Chinese-English Dictionary, Foreign Language Teaching and Research Press, Beijing, 2003 R21 Zong-Guo Huang and Mei-Ling Jin, Dictionary of/ Marine Biology, Ocean Press, Beijing, 1994 (in Chinese) R22 Wenbao Chang, et al., Dictionary of Chemistry, Science Press, Beijing, 2008 (in Chinese)

(Book References 11) R23 Hua-Shi Guan and Shu-Guang Wang, Zhong-hua Hai-yang Ben-cao, Marine Natural Products, 3 Volumes, Chemical Industry Press and Shanghai Science and Technology Press, Beijing, 2009 (in Chinese) R24 C. J. Alexopoulos, M. Blackwell and C. W. Mims, (Yijian Yao and Yu Li translated), Introductory Mycology, Fourth Edition, John Wiley & Sons, Inc., 1996, Chinese Agricultural Press, Beijing, 2002 R25 Janet S. Dodd, The ACS Style Guide, A Manual for Authors and Editors, 2nd Edition, American Chemical Society, Washington, DC, 1997 R26 Shu-Xian Ren, Invertebrates, 2 volumes, Peking University Press, Beijing, 1990 (in Chinese) R27 R. Mcneill Alexander, (translated by Lan-zhi Du), The invertebrates, Chemical Industry Press, Beijing, 2013 (in Chinese) R28 Yanghua Yi and Binghua Jiao, Modern Marine pharmacology, Science Press, Beijing, 2006 (in Chinese) R29 Chang-Yun Wang and Chang-Lun Shao, Marine pharmacology, Science Press, Beijing, 2011 (in Chinese) R30 Rensheng Xu, et al., Chemistry of Natural Products, 2nd Edition, Science Press, Beijing, 2004 (in Chinese) R31 Yue-Zeng Chen, General Biology, Higher Education Press, Beijing, 1997 (in Chinese) R32 Jiaju Zhou, Guirong Xie and Xinjian Yan, Encyclopedia of traditional Chinese Medicines, Molecular Structures, Pharmacological Activities, Natural Sources and Applications, Vol. 1–Vol. 6, Springer, Heidelberg Dordrecht London New York, 2011 R33 Jiaju Zhou, Guirong Xie and Xinjian Yan, TCM Series of Active Components, 10 books, Science Press, Beijing, 2012 (in Chinese)

How to Use the HAMNP Books In essence, from data computerization point of view, scientific knowledge is the expression of interrelation between research objects in different types. During a long coastline without computer, people learn and spread scientific knowledge in traditional ways, including education, reading, and exchanging information with each other. In today’s world, using computer’s powerful functions, we have a new way to learn systematical, complete knowledge. In short, a study process in the new way is to search and learn some relationships. Next, we discuss concretely how to use the HAMNP books. In these books, there are three kinds of data and three pairs of important relations. Three kinds of data are: (1) marine living sources (source); (2) secondary metabolites (compounds); and (3) pharmacological activities (pharm-activity). The three pairs of important relations are: (1) relationship between source and compounds; (2) relationship between compounds and pharm-activity; and (3) relationship between source and pharm-activity. In the case of asking questions, each relation has two directions; hence, together there are six types of questions: Type 1: from known source to unknown compound Type 2: from known compound to unknown source Type 3: from known compound to unknown pharm-activity Type 4: from known pharm-activity to unknown compound Type 5: from known source to unknown pharm-activity Type 6: from known pharm-activity to unknown source (Figure 1) S ource (s) Type 1

Type 5

Type 2

T ype 6

C om pound(s)

T ype 4

P harm-activity

T ype 3

Figure 1: Kinds of Data and Six Types of Questions.

(1) An Illustration of Type 1 (and Type 3, Type 5) Question Up to now, what alkaloids in volume 3 are isolated from sponges of genus Agelas? From index 3 of volume 3, one will get the following related data in detail: Agelas cf. nemoechinata 507. Agelas cf. mauritiana 449, 454, 471. https://doi.org/10.1515/9783110655193-204

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Agelas clathrodes 344, 460, 461, 464, 468, 474, 478, 479, 480, 481, 483, 506, 506, 507, 509. Agelas conifera 344, 449, 454, 468, 469, 471, 474, 478, 479, 480, 481, 506, 507, 509. Agelas dendromorpha 446. Agelas dispar 462, 463, 478, 479, 480, 481, 485, 506, 509, 1124. Agelas flabelliformis 344. Agelas linnaei 335, 336, 337, 338. Agelas longissima 478, 479, 480, 481, 506, 506, 509. Agelas mauritiana 345, 468, 487, 488, 506, 507. Agelas nakamurai 445, 449, 469, 481, 504, 505, 509, 509, 510, 511, 512. Agelas novaecaledoniae 449, 509. Agelas oroides 238, 239, 344, 345, 506, 519. Agelas sceptrum 506, 509. Agelas schmidti 509. Agelas sp. 64, 470, 485, 487, 490, 491, 500, 501, 502, 503. Agelas sp. SS-1003 449, 454, 471, 477, 488, 492, 493, 494, 495, 496, 497, 498, 499, 506, 517, 519. Agelas sventres 516. Agelas wiedenmayeri 506. Since all of compounds 1–1162 in volume 3 are alkaloids, the following 57 compounds (64, 238, 239, 335, 336, 337, 338, 344, 345, 446, 449, 454, 460–464, 468–471, 474, 477–481, 483, 485, 487, 488, 490–507, 509–512, 516, 517, 519, and 1124) are answers to the current question. Then, readers can enjoy studying these 57 compounds by reading the book, including their pharm-activity (question of types 3 and 5). For example, with entry 506 (E)-Oroidin, a reader will know that the compound had already been isolated from following sponges in genus Agelas: Agelas conifera (Caribbean, yield = 2.1% dw), Agelas dispar (Caribbean, yield = 4.2% dw), Agelas clathrodes (Caribbean, yield = 2.1% dw), Agelas longissima (Caribbean, yield = 4.1% dw), Agelas sp. SS-1003 (off Seragaki, Okinawa), Agelas oroides, Agelas conifera, Agelas longissima, Agelas mauritiana, Agelas clathrodes, Agelas wiedenmayeri, Agelas sceptrum, and from other sponges Axinella verrucosa,

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Axinella damicornis, Hymeniacidon sp., Pseudaxinyssa cantharella, Acanthella carteri and Acanthella aurantiaca. And (E)-Oroidin has the following pharmacological activities: Antibacterial (Micrococcus luteus, MIC = 4.07 μg/mL; Bacillus subtilis, MIC = 8.33 μg/mL; Escherichia coli, MIC = 33.3 μg/mL); antibacterial (Staphylococcus aureus ATCC 25923, IC50 = 0.96 μmol/L, Staphylococcus aureus ATCC 9144, IC50 = 1.2 μmol/L, Bacillus subtilis ATCC 6051, IC50 = 2.0 μmol/L, Bacillus subtilis ATCC 6633, IC50 = 0.62 μmol/L, Escherichia coli ATCC 11775, IC50 = 0.55 μmol/L, Pseudomonas aeruginosa ATCC 10145, IC50 = 1.4 μmol/L); antifungal (Candida albicans ATCC 90028, IC50 = 6.3 μmol/L); protein phosphatase 2A inhibitor (IC50 = 50 μmol/L); antibacterial (gram-positive and gram-negative bacteria, MIC ≈ 60 μg/mL, moderate); adrenergic antagonist; serotonin antagonist; antimuscarinic; antifoulant; antihistaminic (gpg ileum, apparent affinity of antagonistic effect pD2 = 4.02 ± 0.11, nonspecific noncompetitive effect); IL-8 Rα receptor inhibitor (IC50 = 9.6 μmol/L); IL-8 Rβ receptor inhibitor (IC50 = 10.8 μmol/L); protein kinase C inhibitor (IC50 = 4.8 μmol/L); antimalarial (Plasmodium falciparum K1 strain, IC50 = 3.9–7.9 μg/mL, MMOA: FabI inhibition).

Br

O N H

N H2N

N H

1

N H

Br

(2) An Illustration of Type 4 (and Type 2, Type 6) Question “What are isolated alkaloids in volume 3 with pharmacological activity antitrypanosomal? And what are their marine sources ?”

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How to Use the HAMNP Books

Table 2: Answer to the Above Type 4 Question. Vol. 

Code Compound Name  Convolutamine I

Structure

Related Sources

O Br

Br

N H

Br



Bryozoan Amathia tortuosa (Bass Strait, Tasmania, Australia)

N

 Didemnidine A

N H

N

H H

H

H

N H



N

H

 Didemnidine B

O

O

N H



H

N H

Br

. . .. . . . . .. . . . . .. . .

Ascidian Didemnum sp. (Tiwai Pt, Southland, New Zealand)

O

O

H

N

H H

Ascidian Didemnum sp. (Tiwai Pt, Southland, New Zealand)

H N

. . .. . .

. . .. . .

 Zamamidine A

Sponge Amphimedon sp. SS- (Seragaki, Okinawa)

HN N

N H H

H

N OH

N HN



 Zamamidine C

Sponge Amphimedon sp. (Seragaki, Okinawa)

HN N

N H H

H

H



N OH

N N

 Mariline A O O

N O

O

O

Marine-derived fungus Stachylidium sp. from sponge Callyspongia cf. flammea (location unspecified)

How to Use the HAMNP Books

XXIII

To browse Index 5 of volume 3, searching “Antitrypanosomal,” the following results were obtained: Antitrypanosomal, Trypanosoma brucei brucei 8, 93, 94, 901, 936, 938, 1089. Antitrypanosomal, Trypanosoma brucei rhodesiense 10, 11, 876, 877. Antitrypanosomal, Trypanosoma brucei selective 180, 181. Antitrypanosomal, Trypanosoma brucei subsp. rhodesiense 852. Further, from the entry bodies of the 14 compounds, all their sources can be obtained (see Table 2). In summary, by using three parts of the books – the contents (ordered by structural classifications), the text (8,350 compound entries in volumes 1–8), and the indexes – readers can easily gain well-formatted systematically related knowledge in multidisciplinary fields.

List of Abbreviations and Acronyms [3H]AMPA [3H]CGS-19755 [3H]CPDPX [3H]DPDPE [3H]KA ‡ 3Y1 5-FU 6-MP 6-OHDA AAI ABRCA ABTS•+ ACAT ACE AChE ACTH ADAM9 ADAM10 ADM AGE AIDS AKT AKT1 ALK AMPB AP-1 APOBEC3G aq ARCA ARK5 ATCC ATPase Aurora-B AXL AZT BACE BACE1 BCG Bcl-2 BoMC BoMCL bp c CaMKIII cAMP CAPE

[3H]-1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid N-methyl-D-aspartic acid (NMDA) receptor antagonist [3H]-1,3-dipropyl-8-cyclopentylxanthine opioid peptide [3H]-kainic acid homonym mark rat fibroblasts 5-fluorouracil 6-mercaptopurine 6-hydroxydopamine antioxidant activity index (final DPPH concentration/EC50) amphotericin B-resistant Candida albicans 2,2′-azino-bis-(3-ethyl benzthiazoline 6-sulfonic acid), radical Acyl-CoA: cholesterol acyl transferase angiotensin-converting enzyme acetylcholinesterase adrenocorticotropic hormone ADAM9 protease ADAM10 protease adriamycin advanced glycation end products acquired immune deficiency syndrome ribosomal protein protein kinase protein kinase amphotericin B transcription factor hmn innate intracellular antiviral factor (recombinant protein) aqueous solution amphotericin-resistant Candida albicans protein kinase American Type Culture Collection adenosine triphosphatase protein kinase protein kinase 3′-azido-3′-deoxythymidine β-secretase β-secretase Bacille Calmette-Guérin a cell survival promoting factor further abbreviation on Bioorg. Med. Chem. further abbreviation on Bioorg. Med. Chem. Lett. boiling point concentration protein kinase cyclic adenosine monophosphate caffeic acid phenethyl ester

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List of Abbreviations and Acronyms

caspase-3 CB CC50 CCR5 CD Cdc2 Cdc25 Cdc25a Cdc25b CDDP CDK CDK1 CDK2 CDK4 CDK4/cyclin D1 P25 p25 CDK7 c-erbB-2 CETP cGMP CGRP ChAT CMV CNS COMPARE ConA COX-1 COX-2 CPB cPLA2 CPT CRPF CRPF FcM29 CSPF Cyp1A CYP1A CYP450 1A d D Delta DGAT DHFR DMSO DNA DOX DPI DPPH

caspase-3 protein cytochalasin B IC50 of cytotoxicity (concentration of the 50% cytotoxic effect) chemokine receptor 5 concentration required to double the specific activity cyclin-dependent kinase protein Cdc25 phosphatase protein phosphatase recombinant hmn phosphatase cis-diaminedichloroplatinum (cisplatin) cyclin-dependent kinase protein kinase protein kinase protein kinase cyclin-dependent kinase 4 (CDK4) in complex with its activator cyclin D1 protein kinase protein kinase protein kinase protein kinase cholesteryl ester transfer protein cyclic guanylic acid, cyclic guanosine monophosphate calcitonin gene-related peptide choline acetyltransferase CMV protease central nervous system COMPARE is an algorithm to analyze data concanavalin A cyclooxygenase-1 cyclooxygenase-2 further abbreviation on Chem. Pharm. Bull. cytosolic 85 kDa phospholipase camptothecin chloroquine-resistant Plasmodium falciparum chloroquine-resistant Plasmodium falciparum FcM29 chloroquine-sensitive Plasmodium falciparum aromatase cytochrome P450 1A cytochrome P450 1A cytochrome P450 1A day diameter (mm) difference in log10 GI50 (mol/L) value of the most sensitive cell line and MG-MID value diacylglycerol acyltransferase dihydrofolate reductase dimethyl sulfoxide deoxyribonucleic acid doxorubicin diphenylene indonium 1,1-diphenyl-2-picrylhydrazyl free radical

List of Abbreviations and Acronyms

DRPF DRS DSPF DYRK1A EBV EC EC50 ED50 ED50 EGF EGFR EL-4 ELISA EPI ERK ESBLs EurJOC FAK FBS FLT3 Flu-A Flu-B fMLP/CB FOXO1a fp FPT FRCA FtsZ FXR GABA GI50 GlyR gp41 gpg GPR12 GRP78 GST GTP GU4 GU5 h H1N1 H3N2 H5N1 HBV HC50 HCMV

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drug-resistant Plasmodium falciparum drug-resistant Staphylococcus sp. drug-sensitive Plasmodium falciparum protein kinase Epstein–Barr virus effective concentration medium effective concentration effective dose for 50% medium effective dose (sometimes for the medium effective concentration) epidermal growth factor epidermal growth factor receptor lymphoma cell line with resistance to natural killer cells enzyme-linked immunosorbent assay epirubicin extracellular signal-regulated protein kinase extended spectrum β-lactamase further abbreviation on Eur. J. Org. Chem. protein kinase fetal bovine serum a protein tyrosine kinase influenza virus type A influenza virus type B N-formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B downstream target of PTEN tumor suppressor freezing point farnesyl protein transferase fluconazole-resistant Candida albicans a structural homolog of eukaryotic tubulin, a GTPase farnesoid X receptor γ-aminobutyric acid the concentration of sample necessary to inhibit the growth to 50% of the control glycine-gated chloride channel receptor a transmembrane protein of HIV-1 (recombinant protein) guinea pig G protein-coupled receptor 12; it can be a significant molecular target for treating a variety of neurological disorders molecular chaperone (chaperone) glutathione S-transferases guanosine triphosphate Candida albicans-sensitive GU4 strain Candida albicans-resistant GU5 strain hour influenza virus H1N1 influenza virus H3N2 influenza virus A H5N1 hepatitis B virus medium hemolytic concentration hmn cytomegalovirus

XXVIII

HCV HD HER2 HF HIF-1 HIV HIV-1 HIV-1 IIIB HIV-1 in HIV-1 RF HIV-1-rt HIV-2 HIV-rt HLE HMG-CoA hmn HNE HO• hPPARd HSV HSV-1 HSV-2 hTopo l HXB2 IC IC50 IC90 IC100 ICR ID ID50 IDE IDO IFV IgE IGF1-R IgM IL IL-1 IL-1α IL-1β IL-2 IL-4 IL-5 IL-6 IL-8 IL-12 IL-13

List of Abbreviations and Acronyms

hepatitis C virus a positive control compound, no concrete explanation in original paper (J. Qin, et al, BoMCL, 2010, 20, 7152) tyrosine kinase hypersensitivity factor hypoxia inducible factor-1 hmn immunodeficiency virus hmn immunodeficiency virus type 1 hmn immunodeficiency virus type 1 IIIB hmn immunodeficiency virus type 1 integrase hmn immunodeficiency virus RF hmn immunodeficiency virus type 1 reverse transcriptase hmn immunodeficiency virus type 2 hmn immunodeficiency virus reverse transcriptase hmn leukocyte elastase 3-hydroxy-3-methylglutaryl coenzyme A reductase human hmn neutrophil elastase hydroxyl radical hmn peroxisome proliferator-activated receptor delta herpes simplex virus herpes simplex virus 1 herpes simplex virus 2 hTopo l isomerase T-cell tropic viral strain inhibiting concentration median inhibiting concentration inhibiting concentration for 90% absolute inhibiting concentration imprimting control region mouse inhibition diameter (mm) median inhibiting dose insulin-degrading enzyme indoleamine 2,3-dioxygenase influenza virus immunoglobulin E protein kinase immunoglobulin M interleukin interleukin-1 interleukin-1α interleukin-1β interleukin-2 interleukin-4 interleukin-5 interleukin-6 interleukin-8 interleukin-12 interleukin-13

List of Abbreviations and Acronyms

IM IMPDH IN iNOS InRt ip iv IZ IZD IZR JACS Jak2 JCS Perkin I JMC JNK JNP JOC KDR KU-812 LAV LC50 LCV LD LD100 LD50 LD99 LDH LOX LPS LTB4 LTC4 LY294002 MABA MAGI test MAPKAPK-2 MAPKK MBC MBC90 MBEC90 MCV MDR MDR1 MDRPF MDRSA MDRSP MEK1 wt MET wt

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immunomodulator inosine monophosphate dihydrogenase integrase inducible nitric oxide synthase inhibitive rate intraperitoneal injection intravenous injection inhibition zone (mm) inhibition zone diameter (mm) inhibition zone radii (mm) further abbreviation on J. Am. Chem. Soc. Janus kinase 2 further abbreviation on J. Chem. Soc., Perkin Trans. I further abbreviation on J. Med. Chem. c-Jun NH2-terminal kinase further abbreviation on J. Nat. Prod. further abbreviation on J. Org. Chem. a protein tyrosine kinase hmn basophilic granulocyte T-cell tropic viral strain concentration at which only 50% of the cells are viable lymphocyte viability lethal dose 100% lethal dose medium lethal dose 99% lethal dose lactate dehydrogenase lipoxygenase lipopolysaccharide leukotriene B4 leukotriene C4 phosphatidylinositol-3-kinase inhibitor, used as a positive control in anti-inflammatory assay microplate Alamar blue assay also called single life cycle test, reflects only one round of infection mitogen-activated protein kinase-activated protein kinase 2 mitogen-activated protein kinase kinase minimum bactericidal concentration minimum bactericidal concentration for 90% minimum biofilm eradication counts for 90% poxvirus Molluscum contagiosum virus multidrug resistance major facilitator superfamily 1; one type of efflux pump in C. albicans, which functions as an H+-antiporter multidrug-resistant Plasmodium falciparum multidrug-resistant Staphylococcus aureus multidrug-resistant Streptococcus pneumoniae protein kinase protein kinase

XXX

MG-MID MIA MIC MIC50 MIC80 MIC90 MID min MLD MLR MMOA MMP MMP-2 MoBY-ORF mp MPtpA MPtpB mPTPB MREC MRSA MRSE MSR MSSA MSSE MT1-MMP MT4 MTT MTT assay mus n nACh NADH NDM-1 NEK2 NEK6 NF-κB

NFRD NGF NMDA NO• NPR O2•− ONOO− ORAC orl p24

List of Abbreviations and Acronyms

mean value of log10 GI50 (mol/L) over all cell lines tested minimal inhibitory amounts (μg/disk) minimum inhibitory concentration minimal inhibitive concentration for 50% minimal inhibitive concentration for 80% minimal inhibitive concentration for 90% minimum inhibitory dose minute minimum lethal dose mixed lymphocyte reaction molecular mechanism of action matrix metalloproteinases matrix metalloproteinase-2 molecular barcoded yeast open-reading frame library method melting point mycobacterial protein tyrosine phosphatase A mycobacterial protein tyrosine phosphatase B Mycobacterium tuberculosis protein tyrosine phosphatase B methicillin-resistant Escherichia coli methicillin-resistant Staphylococcus aureus methicillin-resistant Staphylococcus epidermidis macrophage scavenger receptor methicillin-sensitive Staphylococcus aureus methicillin-sensitive Staphylococcus epidermidis membrane type 1 matrix metalloproteinase MT4 cells containing HIV-1 IIIB virus 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide a cytotoxicity measurement method, tetrazolium-based colorimetric assay, see L. V. Rubinstein, et al., Nat. Cancer Inst., 82, 1113–1118 (1990) mouse number of parallel experiments nicotinic acetylcholine reduced nicotinamide adenine dinucleotide New Delhi metallo-β-lactamase-1 protein kinase protein kinase NF-κB serves as a central regulator of hmn immune, inflammatory, and antiapoptotic responses (Ghosh et al., 1998, Ann. Rev. Immunol, 16, 225–260) NADH-fumarate reductase nerve growth factor N-methyl-D-aspartate nitric oxide free radical further abbreviation on Nat. Prod. Rep. superoxide free radical peroxy nitrite free radical oxygen radical absorbance capacity oral p24 protein

List of Abbreviations and Acronyms

P2Y receptors P2Y11 receptor P450 p56lck PAcF PAF PD pD2 (= pEC50) PDE5 PDGF PfGSK-3 Pfnek-1 PfPK5 PfPK7 PGE2 PHK PIM1 PK PKA PKC PKC-ε PKD PKG PLA PLA2 PLCγ1 PLK1 PM PMA (=TPA) PMNL PP PP1 PP2A pp60V-SRC PPAR PPDK PR PRK1 PRNG PRSP PTEN PTK PTP1B PTPB PTPS2

XXXI

one type of purine receptors which includes P1 (adenosine receptors) and P2 receptors [ionotropic P2X and metabotropic (G protein-coupled) P2Y] one of eight P2Y subtypes cytochrome P450 tyrosine kinase platelet activating factor platelet aggregation factor Parkinson’s disease negative logarithm (−log M) of molar concentration required to produce 50% of the maximum response (EC50) phosphodiesterase 5 platelet-derived growth factor kinase a NIMA-related protein kinase of Plasmodium falciparum kinase kinase prostaglandin E2 primary hmn keratinocytes protein kinase protein kinase protein kinase A protein kinase C protein kinase C-ε ribosomal protein protein kinase G phospholipase A phospholipase A2 ribosomal protein protein kinase further abbreviation on Planta Med. phorbol-12-myristate-13-acetate hmn polymorphonuclear leukocyte protein phosphatase protein phosphatase PP1 protein phosphatase PP2A tyrosine kinase peroxisome proliferator-activated receptor pyruvate phosphate dikinase protease protein kinase penicillin-resistant Neisseria gonorrhoeae penicillin-resistant Staphylococcus pneumoniae tumor suppressor, an identified tumor suppressor gene located on hmn chromosome 10q23.3 protein tyrosine kinase protein tyrosine phosphatase 1B, an important target for treatment of type II diabetes protein tyrosine phosphatase B protein tyrosine phosphatase S2

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List of Abbreviations and Acronyms

PV-1 PXR QR Range rat rbt RLAR RNA ROS RS321 RSV RT RU RyR1-FKBP12 S6 SAK SARS ScRt SF162 SI SI SI SI SI SIRT2

sp. spp. SR SRB SRC SV40 Syn. T/C TACE Taq DNA polymerase TBARS TC50 TEAC TGI TMV TNFα TPA (=PMA)

Polio virus pregnane X receptor NAD(P)H: quinone reductase difference in log10 GI50 (mol/L) value of the most sensitive cell line and the least sensitive cell white rat rabbit rat lens aldose reductase ribonucleic acid reactive oxygen species (involved in genesis of various cancers, arteriosclerosis, rheumatism, and aging) code of a yeast respiratory syncytial virus reverse transcriptase response unit of binding capacity to HIV-1 targets, 1 RU = 1 pg/mm2 RyR1-FKBP12 Ca2+ channel, a tetrameric heterodimeric channel protein (~2000 kDa) associated with smaller 12 kDa immunophilin FKBP12 ribosomal protein a protein kinase severe acute respiratory syndrome scavenging rate macrophage-tropic viral strain IC50 of testing cells/IC50 of HUVECs selective index = cytotoxic CC50/target EC50 selective index = cytotoxic IC50/target IC50 selective index = cytotoxic IC50/target MIC selective index = cytotoxic TC50/target IC50 hmn sirtuin type 2 (a NAD+-dependent cytoplasmic protein that is colocalized with HDAC6 on microtubules. SIRT2 has been shown to deacetylate α-tubulin and to control mitotic exit from the cell cycle) species species (plural) sarcoplasmic reticulum sulforhodamine B assay protein kinase SV40 virus synonym survival ratio [survival time of treated animal (T) was compared to that of control animal (C) expressed as a percent (T/C%)] α-secretase (a serine protease) a DNA polymerase isolated from the thermophilic bacterium Thermus aquaticus thiobarbituric acid-reactive substance assay 50% cytotoxic concentration Trolox equivalent antioxidant capacity 100% growth inhibition tobacco mosaic virus tumor necrosis factor-α 12-O-tetradecanoyl phorbol 13-acetate

List of Abbreviations and Acronyms

TPK TRP TRPA1 TRPV1 TRPV3 TXB2 TZM-bl USP7 VCAM VCAM-1 VCR VEGF VEGF-A VEGFR2 VE-PTP VGSC VHR Vif VP-16 VRE VREF VSE VSSC VSV WST-8 XTT YU2-V3

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tyrosine protein kinase transient receptor potential cationic channel transient receptor potential cationic channel of subfamily A1 transient receptor potential cationic channel of subfamily V1 transient receptor potential cationic channel of subfamily V3 thromboxane B2 host cell in HIV-1 neutralization assay a deubiquitylating enzyme hydrolyzing isopeptide bond at C-terminus of ubiquitin is an emerging cancer target vascular cell adhesion molecule vascular cell adhesion molecule-1 vincristine vascular endothelial growth factor vascular endothelial growth factor A tyrosine kinase VEGFR2 protein phosphatase voltage-gated sodium channel vaccinia open-reading frame H1-related protein phosphatase viral infectivity factor of HIV-1 etoposide (Sigma product), a positive control for cytotoxic assay vancomycin-resistant Enterococcus sp. vancomycin-resistant Enterococcus faecium vancomycin-sensitive Enterococcus sp. voltage-sensitive sodium channel Vesicular stomatitis virus 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfo-phenyl)2H-tetrazolium, monosodium salt sodium 3′-[1-(phenylaminocarbonyl)-3,4-tetrazolium] bis(4-methoxy-6nitrobenzene)sulfonic acid viral strain

List of Cancer Cell Codes This set of codes for 438 cancer cells, named as CCC codes, are defined and tried out in the books by the author. The codes of some normal cells are also listed below. 293T 3T3-L1 5637 786-0 9KB A-10 A2058 A278 A2780 A2780CisR A2780/DDP A2780/Tax A375 A375-S2 A431 A498 A549 A549 NSCL A549/ATCC ACC-MESO-1 ACHN AGS AsPC-1 B16 B16F1 B16-F-10 BC BC-1 BCA-1 BEAS2B Bel7402 BG02 BGC823 BOWES BR1 BSC BSC-1 BSY1 BT-483 BT549 BT-549 BXF-1218L BXF-T24 BXPC

kidney epithelial cells murine fibroblasts superficial bladder cancer (cell) hmn renal cancer (cell) hmn epidermatoid nasopharyngeal carcinoma (cell) rat aorta cells hmn (cell) hmn ovarian tumor (cell) hmn ovarian tumor (cell) hmn ovarian tumor (cell) hmn ovarian tumor (cell) hmn ovarian tumor (cell) hmn melanoma (cell) hmn melanoma (cell) hmn epidermic cancer (cell) hmn renal cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn malignant pleural mesothelioma (cell) hmn renal cancer (cell) gastric adenocarcinoma (cell) hmn pancreatic cancer (cell) mouse melanoma (cell) mouse melanoma (cell) mouse melanoma (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) normal hmn lung bronchial cells hmn liver cancer (cell) normal hmn embryonic stem cells hmn gastric cancer (cell) hmn cells DNA repair competent Chinese hamster ovary (cell) normal monkey kidney cells normal African Green Monkey kidney cells breast cancer (cell) hmn breast carcinoma (cell) hmn galactophore cancer (cell) hmn breast cancer (cell) hmn bladder cancer (cell) hmn bladder cancer (cell) hmn pancreas cancer (cell)

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BXPC3 C6 C26 C38 CA46 Ca9-22 CaCo-2 CAKI-1 Calu Calu3 CCRF-CEM CCRF-CEMT CEM CEM-TART CFU-GM CHO CHO-K1 CML K562 CNE CNE2 CNS SF295 CNXF-498NL CNXF-SF268 Colo320 Colo357 Colon26 Colon38 Colon205 Colon250 CV-1 CXF-HCT116 CXF-HT29 DAMB DG-75 DLAT DLD-1 DLDH DMS114 DMS273 Doay Dox40 DU145 DU4475 E39 EAC EKVX EM9 EMT-6 EPC

List of Cancer Cell Codes

hmn pancreas cancer (cell) rat glioma (cell) hmn colon carcinoma (cell) murine colon adenocarcinoma (cell) hmn Burkitt’s lymphoma (cell) hmn gingival carcinoma (cell) hmn epithelial colorectal adenocarcinoma (cell) hmn renal cancer (cell) prostate carcinoma (cell) nonsmall cell lung cancer (cell) hmn T-cell acute lymphoblastic leukemia (cell) leukemia (cell) hmn leukemia (cell) T cells that express both HIV-1 tat and rev hmn/murine hematopoietic progenitor cells Chinese hamster ovary cells subclone of normal Chinese hamster ovary cells chronic myelogenous leukemia (cell) hmn nasopharyngeal carcinoma (cell) hmn nasopharyngeal carcinoma (cell) hmn brain tumor (cell) hmn glioblastoma cancer (cell) hmn glioblastoma cancer (cell) hmn colorectal cancer (cell) hmn colorectal cancer (cell) colorectal cancer (cell) mus colorectal cancer (cell) colorectal cancer (cell) colorectal cancer (cell) monkey kidney fibroblasts hmn colon cancer (cell) hmn colon cancer (cell) hmn mammary carcinoma (cell) hmn B lymphocyte (cell) Dalton’s lymphoma ascites tumor (cell) hmn colorectal adenocarcinoma (cell) hmn colorectal adenocarcinoma (cell) hmn lung cancer (cell) hmn small cell lung cancer (cell) hmn medulloblastoma (cell) hmn myeloma (cell) prostate cancer (cell) breast cancer (cell) hmn renal carcinoma (cell) Ehrlich ascites carcinoma (cell) hmn nonsmall cell lung cancer (cell) topoisomerase I-sensitive Chinese hamster ovary (cell) mouse tumor cells carp epithelium (cell)

List of Cancer Cell Codes

EVLC-2 F1 FADU Farage Fem-X Fl FM3C G402 GM7373 GR-III GXF-251L H116 H125 H441 H460 H522 H1299 H1325 H1975 H2122 H2887 H69AR H929 H9c2 HBC4 HBC5 HBL100 HCC366 HCC2998 HCC-S102 HCT HCT8 HCT15 HCT29 HCT116 HCT116/mdr+ HCT116/topo HCT116/VM46 HEK-293 HEL HeLa HeLa-APL HeLa-S3 Hep2 Hep3B HepA Hepa1c1c7 HepG HepG2

SV40 large T-antigen immortalized hmn umbilical vein cells hmn amniotic epithelial cells pharynx-sq cancer (cell) hmn lymphoma (cell) melanoma (cell) hmn amniotic epithelial cell line mus mammary tumor (cell) hmn renal leiomyoblastoma bovine endothelial (cell) adenocarcinoma (cell) hmn stomach cancer (cell) hmn colorectal cancer (cell) hmn colorectal cancer (cell) hmn lung adenocarcinoma (cell) hmn lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn lung adenocarcinoma (cell) hmn nonsmall cell lung cancer (cell) hmn cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) multidrug-resistant small cell lung cancer (cell) hmn myeloma (cell) rat cardiac myoblasts breast cancer (cell) breast cancer (cell) breast cancer (cell) hmn nonsmall cell lung cancer (cell) hmn colorectal cancer (cell) hepatocellular carcinoma (cell) hmn colorectal cancer (cell) hmn colorectal cancer (cell) hmn colorectal cancer (cell) hmn colon adenocarcinoma (cell) hmn colorectal cancer (cell) overexpress mdr+ hmn colorectal cancer (cell) resistant to etoposide hmn colorectal cancer (cell) multidrug-resistant colorectal cancer (cell) normal hmn epithelial kidney cells hmn embryonic lung fibrocytes hmn cervical epithelial carcinoma (cell) hmn cervical epithelial cancer (cell) hmn cervical epithelial cancer (cell) hmn liver carcinoma (cell) hmn liver cancer (cell) hmn liver cancer ascites (cell) mus liver cancer (cell) hmn liver cancer (cell) hmn liver cancer (cell)

XXXVII

XXXVIII

HepG3 HepG3B HEY HFF HL60 HL7702 HLF HM02 HMEC HMEC1 HNXF-536L HOP-18 HOP-62 HOP-92 Hs578T Hs683 HSV-1 HT HT29 HL60 HT115 HT460 HT1080 HTC116 HTCLs HuCCA-1 Huh7 HUVEC HUVECs IC-2WT IGR-1 IGROV IGROV1 IGROV-ET IMR-32 IMR-90 J774 J774.1 J774.A1 JB6 CI41 JB6 P+CI41 JurKat JurKat-T K462 K562 KB KB16 KB-3 KB-3-1

List of Cancer Cell Codes

hmn liver cancer (cell) hmn liver cancer (cell) hmn ovarian carcinoma (cell) hmn foreskin fibroblasts hmn promyelocytic leukemia (cell) hmn liver tumor (cell) hmn lung fibroblasts hmn gastric adenocarcinoma (cell) hmn microvascular endothelial cells hmn microvascular endothelial cells hmn head and neck cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn breast cancer (cell) hmn oligodendroglioma (black dots) (cell) nonmalignant cell hmn lymphoma (cell) hmn colorectal cancer (cell) M. Daferner, et al., Z. Naturforsch., Teil C, 1999, 54, 474 hmn colorectal cancer (cell) hmn tumor (cell) hmn fibrosarcoma (cell) hmn acute promyelocytic leukemia (cell) hmn tumors (cells) hmn cholangiocarcinoma cancer (cell) hmn hepatoma (cell) hmn umbilical vein endothelial cell hmn umbilical vein endothelial cell murine cell line hmn melanoma (cell) hmn ovarian cancer (cell) hmn ovarian cancer (cell) hmn ovarian cancer (cell) hmn neuroblastoma (cell) hmn diploid lung fibroblasts mus monocyte/macrophage (cell) mus monocyte/macrophage (cell) mus monocyte/macrophage (cell) mouse epidermal cells mouse epidermal cells hmn leukemia (cell) hmn T-cell leukemia (cell) hmn leukemia (cell) hmn chronic myelogenous leukemia (cell) hmn nasopharyngeal carcinoma (cell) hmn nasopharyngeal carcinoma (cell) hmn epidermoid carcinoma (cell) hmn epidermoid carcinoma (cell)

List of Cancer Cell Codes

KB-C2 KB-CV60 KBV200 Ketr3 KM12 KM20L2 KMS34 KU812F KV/MDR KYSE30 KYSE70 KYSE180 KYSE520 L1210 L1210/Dx L363 L-428 L5178 L5178Y L-6 L929 LLC-PK1 LMM3 LNCaP LO2 LoVo LoVo-DOX LOX LOX-IMVI LX-1 LXF-1121L LXF-289L LXF-526L LXF-529L LXF-629L LXFA-629L LXF-H460 M14 M16 M17 M17-Adr M21 M5076 MAGI MALME-3 MALME-3M MAXF-401 MAXF-401NL MAXF-MCF7

hmn carcinoma (cell) hmn carcinoma (cell) MDR nasopharyngeal carcinoma (cell) hmn renal cancer (cell) hmn colorectal cancer (cell) hmn colorectal cancer (cell) hmn myeloma (cell) hmn leukemia (cell) multidrug-resistant cancer (cell) hmn esophageal cancer (cell) hmn esophageal cancer (cell) hmn esophageal cancer (cell) hmn esophageal cancer (cell) mouse lymphocytic leukemia (cell) doxorubicin-resistant L1210 (cell) hmn myeloma (cell) leukemia (cell) mouse lymphosarcoma (cell) mouse lymphosarcoma (cell) rat skeletal myoblasts (cell) mouse fibroblasts pig kidney cells mouse mammary adenocarcinoma (cell) hmn prostate cancer (cell) hmn liver cells hmn colorectal cancer (cell) hmn colorectal cancer (cell) hmn melanoma (cell) hmn melanoma (cell) hmn lung cancer (cell) hmn lung cancer (cell) hmn lung cancer (cell) hmn lung cancer (cell) hmn lung cancer (cell) hmn lung cancer (cell) lung adenocarcinoma (cell) hmn lung cancer (cell) melanoma (cell) murine colon adenocarcinoma (cell) adriamycin-resistant breast cancer (cell) adriamycin-resistant breast cancer (cell) melanoma (cell) ovarian sarcoma (cell) Hela-CD4-LTR-β-gal (indicator) cells containing HIV-1 IIIB virus melanoma (cell) melanoma (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell)

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XL

List of Cancer Cell Codes

MCF MCF-10A MCF7 MCF7 Adr MCF7/Adr MCF7/ADR-RES MCF12 MDA231 MDA361 MDA435 MDA468 MDA-MB MDA-MB-231 MDA-MB-231/ATCC MDA-MB-435 MDA-MB-435s MDA-MB-468 MDA-N MDCK ME180 MEL28 MES-SA MES-SA/DX5 MEXF-276L MEXF-394NL MEXF-462NL MEXF-514L MEXF-520L MG63 MGC-803 MiaPaCa Mia-PaCa-2 MKN1 MKN7 MKN28 MKN45 MKN74 MM1S Molt3 Molt4 Mono-Mac-6 MPM ACC-MESO-1 MRC-5 MRC5CV1 MS-1 MX-1 N18-RE-105 N18-T62 NAMALWA

hmn breast cancer (cell) hmn breast epithelial (cell) hmn breast cancer (cell) drug-resistant hmn breast MCF7 cancer (cell) drug-resistant hmn breast MCF7 cancer (cell) drug-resistant hmn breast cancer MCF7 (cell) hmn esophageal cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) hmn breast cancer (cell) Madin–Darby canine (cell) cervical cancer (cell) hmn melanoma (cell) hmn uterine (cell) hmn uterine (cell) hmn melanoma (cell) hmn melanoma (cell) hmn melanoma (cell) hmn melanoma (cell) hmn melanoma (cell) hmn osteosarcoma (cell) hmn cancer (cell) hmn pancreas cancer (cell) hmn pancreas cancer (cell) hmn gastric cancer (cell) hmn gastric cancer (cell) hmn gastric cancer (cell) hmn gastric cancer (cell) hmn gastric cancer (cell) hmn myeloma (cell) leukemia (cell) hmn T lymphocyte leukemia (cell) mononuclear cells hmn malignant pleural mesothelioma normal hmn diploid embryonic cells SV40-transformed hmn fibroblasts mice endothelial cells hmn mammary carcinoma xenografts neuronal hybridoma (cell) mus neuroblastoma (cell) leukemia (cell)

List of Cancer Cell Codes

NBT-T2 (BRC-1370) NCI-ADR NCI-ADR-Res NCI-H23 NCI-H69 NCI-H82 NCI-H187 NCI-H226 NCI-H322M NCI-H446 NCI-H460 NCI-H510 NCI-H522 neuro-2a NFF NHDF NIH3T3 NIH3T3 NMuMG NOMO-1 NS-1 NSCLC NSCLC HOP-92 NSCLC-L16 NSCLC-N6 NSCLC-N6-L16 NUGC-3 OCILY17R OCIMY5 OPM2 OVCAR-3 OVCAR-4 OVCAR-5 OVCAR-8 OVXF-1619L OVXF-899L OVXF-OVCAR3 P388 P388/ADR P388/Dox P388D1 PANC1 panc89 PAXF-1657L PAXF-PANC1 PBMC PC12 PC-12 PC3

rat bladder epithelial cells hmn ovarian sarcoma (cell) hmn ovarian sarcoma (cell) hmn nonsmall cell lung cancer (cell) hmn lung cancer (cell) hmn lung cancer (cell) hmn small cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn lung cancer (cell) hmn nonsmall cell lung cancer (cell) hmn lung cancer (cell) hmn nonsmall cell lung cancer (cell) mouse neuroblastoma (cell) nonmalignant neonatal foreskin fibroblasts normal hmn dermal fibroblasts nontransformed fibroblasts normal fibroblasts nontransformed epithelial cells hmn acute myeloid leukemia murine cells hmn bronchopulmonary nonsmall cell lung cancer hmn nonsmall cell lung cancer (cell) hmn bronchopulmonary nonsmall cell lung carcinoma hmn bronchopulmonary nonsmall cell lung cancer (cell) hmn bronchopulmonary nonsmall cell lung carcinoma hmn gastric cancer (cell) hmn lymphoma (cell) hmn myeloma (cell) hmn myeloma (cell) ovarian adenocarcinoma (cell) ovarian adenocarcinoma (cell) ovarian adenocarcinoma (cell) ovarian adenocarcinoma (cell) ovary cancer (cell) ovary cancer (cell) ovary cancer (cell) mus lymphocytic leukemia (cell) P388 adriamycin-resistant (cell) mus leukemia cells expressing resistance toward doxorubicin mus macrophage cells hmn pancreas cancer (cell) pancreatic cancer (cell) hmn pancreas cancer (cell) hmn pancreas cancer (cell) hmn normal peripheral blood mononuclear cells hmn lung cancer (cell) rat pheochromocytoma (cell) hmn prostate cancer (cell)

XLI

XLII

PC3M PC3MM2 PC-9 PRXF-22RV1 PRXF-DU145 PRXF-LNCAP PRXF-PC3M PS (=P388) PV1 PXF-1752L QG56 QGY-7701 QGY-7703 Raji RAW264.7 RB RBL-2H3 RF-24 RKO RKO-E6 RPMI7951 RPMI8226 RXF-1781L RXF-393 RXF-393NL RXF-486L RXF-631L RXF-944L S180 S180A SAS SCHABEL SF268 SF295 SF539 SGC7901 SH-SY5Y SK5-MEL SKBR3 SK-Hep1 SK-MEL-2 SK-MEL-5 SK-MEL-28 SK-MEL-S SK-N-SH SK-OV-3 SMMC-7721

List of Cancer Cell Codes

hmn prostate cancer (cell) hmn prostate cancer (cell) hmn lung cancer (cell) hmn prostate cancer (cell) hmn prostate cancer (cell) hmn prostate cancer (cell) hmn prostate cancer (cell) PS system, P388 mouse lymphocytic leukemia (cell) nonmalignant cell mesothelioma cancer (cell) hmn lung carcinoma (cell) hmn hepatocellular carcinoma (cell) hmn liver cancer (cell) hmn EBV-transformed Burkitt’s lymphoma B cell mouse macrophages hmn prostate cancer (cell) rat basophilic cells papillomavirus 16 E6/E7 immortalized hmn umbilical vein cells hmn colon cancer (cell) hmn colon cancer (cell) hmn malignant melanoma (cell) hmn myeloma (cell) renal cancer (cell) renal cancer (cell) renal cancer (cell) renal cancer (cell) renal cancer (cell) renal cancer (cell) mouse sarcoma (cell) sarcoma 180 ascite cells hmn oral cancer mouse lymphoma cancer (cell) hmn brain tumor (cell) hmn brain tumor (cell) hmn brain tumor (cell) hmn gastric cancer (cell) hmn neuroblastoma (cell) hmn melanoma (cell) hmn breast cancer (cell) hmn liver carcinoma (cell) hmn melanoma (cell) hmn melanoma (cell) hmn melanoma (cell) hmn melanoma (cell) neuroblastoma (cell) ovarian adenocarcinoma (cell) hmn liver cancer (cell)

List of Cancer Cell Codes

SN12C SN12k1 SNB19 SNB75 SNB78 SNU-C4 SR St4 stromal cell SUP-B15 Sup-T1 SW480 SW620 SW1573 SW1736 SW1990 T24 T-24 T47D THP-1 TK10 tMDA-MB-231 tsFT210 TSU-Pr1 TSU-Pr1-B1 TSU-Pr1-B2 U251 U266 U2OS U373 U373MG U-87-MG U937 UACC-257 UACC62 UO-31 UT7 UV20 UXF-1138L V79 Vero WEHI-164 WHCO1 WHCO5 WHCO6 WI26 WiDr

hmn renal cancer (cell) hmn renal cancer (cell) hmn brain tumor (cell) hmn CNS cancer (cell) hmn brain tumor (cell) hmn cancer (cell) leukemia (cell) gastric cancer (cell) bone marrow stromal cells leukemia (cell) T-cell lymphoma cancer cells hmn colorectal adenocarcinoma (cell) hmn colorectal adenocarcinoma (cell) hmn nonsmall cell lung cancer (cell) hmn thyroid cancer (cell) hmn pancreatic cancer (cell) hmn liver cancer (cell) hmn transitional bladder carcinoma (cell) hmn breast cancer (cell) hmn acute monocytic leukemia (cell) hmn renal cancer (cell) hmn breast cancer (cell) mouse cancer (cell) invasive bladder cancer (cell) invasive bladder cancer (cell) invasive bladder cancer (cell) CNS tumor/glioma (cell) myeloma (cell) hmn osteosarcoma (cell) glioblastoma/astrocytoma (cell) hmn brain cancer (cell) caucasian glioblastoma (cell) hmn monocytic leukemia (cell) melanoma (cell) melanoma (cell) hmn renal cancer (cell) hmn leukemia (cell) DNA cross-linking agent-sensitive Chinese hamster ovary (cell) hmn uterus cancer (cell) Chinese hamster (cell) green monkey kidney tumor (cell) mus fibrosarcoma (cell) hmn esophageal cancer (cell) hmn esophageal cancer (cell) hmn esophageal cancer (cell) hmn lung fibroblasts hmn colon adenocarcinoma (cell)

XLIII

XLIV

WMF XF498 XRS-6 XVS ZR-75-1

List of Cancer Cell Codes

hmn prostate cancer (cell) hmn CNS cancer (cell) topoisomerase II-sensitive Chinese hamster ovary (cell) topoisomerase II-sensitive CHO cell hmn breast cancer (cell)

1 Amine Guanidine and Amide Alkaloids 1.1 Amine Alkaloids 1 Calcareous sponge Leucetta Acetylenic Alkaloid Type: Acyclic amines. C19H31NO Source: Calcareous sponge Leucetta sp. (0.088%, depth of 50 m, Kume I., Okinawa). Pharm: Cytotoxic (NBT-T2, IC50 = 2.5 μg/mL). Ref: I. Hermawan, et al, Mar. Drugs, 2011, 9, 382

N OH 7

2 Homopahutoxin Type: Acyclic amines. C24H48NO41+ Source: Boxfish Ostracion immaculatus. Pharm: Haemolytic. Ref: N. Fusetani, et al, Toxicon, 1987, 25, 459 O O

O O

N

+

3 Homotaurine 3-Amino-1-propanesulfonic acid; Tramiprosate Type: Acyclic amines. C3H9NO3S Needles (EtOH aq), mp 290–292 °C, dec 270–271 °C. Source: Red alga Grateloupia livida, red algae spp., green alga Cladophora densa. Pharm: Anti-AD (inhibits amyloid A fibril formation and deposition, Using in treatment of Alzheimer’s disease and cerebral amyloid angiopathy); anti-AD clinical trial (clinical trial is going on: NCT00314912 Last verified, July 2007 Bellus Health Inc., Title: Open-Label Extension of the Phase III Study With Tramiprosate (3APS) in Patients With Mild to Moderate AD. Study Design: Randomized, double-blind, placebo-controlled, parallel-group study conducted at 67 study centers across the United States and Canada. Purpose: Evaluate the long-term safety. Secondary Outcome Measures: To provide additional long-term data on the efficacy of Tramiprosate (3APS). No significant treatment effect). Ref: CRC Press, DNP on DVD, 2012, version 20.2│ P. Russo, et al, Mar. Drugs, 2016, 14, 5 (review) O H 2N

S

O OH

https://doi.org/10.1515/9783110655193-001

2

1 Amine Guanidine and Amide Alkaloids

4 Taurine Aminoethylsulfonic acid Type: Acyclic amines. C2H7NO3S Monoclinic prismatic rods with sharp taste, mp 328 °C, mp 320–325 °C (dec). Source: Green algae Caulerpa okamurai, Caulerpa racemosa, Chlorodesmis comosa, Codium adherens, Codium fragile and Enteromorpha linza, sponges Calyx nicaeensis and Geodia gigas, mussel (blue mussel) Mytilus edulis, eulamellibranch Macrocallista nimbosa, prosobranch Turbo stenogyrus, marine vestimentarian worm Riftia pachyptila, terrestrial higher plants (e.g. leguminous seedlings). Pharm: Adjunct in treatment of hypercholesterolaemia; metabolic regulator; intermedium in metabolism of cysteine; LD50 (mus, scu) = 6000 mg/kg. Ref: CRC Press, DNP on DVD, 2012, version 20.2 O HO

S

O

NH2

5 (2S,3E,5Z)-3,5,13-Tetradecatrien-2-amine Type: Acyclic amines. C14H25N Viscous pale yellow oil, [α]D25 = +17.8° (c = 1, CHCl3) (95% e.e.). Source: Ascidian Pseudodistoma novaezelandiae. Pharm: Cytotoxic. Ref: N. B. Perry, et al, Aust. J. Chem., 1991, 44, 627│ D. Enders, et al, Liebigs Ann. Chem., 1993, 551

NH2

6 Acarnidine C Type: Polyamines. C26H49N5O2 Source: Sponge Acarnus erithacus. Pharm: Antiviral; antimicrobial. Ref: J. -W. Blunt, et al, Tet. Lett., 1982, 23, 2793 NH

O N H

N

N H O

NH2

Z

7 Cathestatin C Type: Polyamines. C18H25N3O6 Source: Marine-derived fungus Microascus longirostris SF-73 from an unidentified sponge (New Zealand). Pharm: Cysteine proteases inhibitor (papain, IC50 = 20.0 nmol/L, Cathepin B, IC50 = 114.3 nmol/L, Cathepin L, IC50 = 11.1 nmol/L). Ref: C. -M. Yu, et al, J. Antibiot., 1996, 49, 395

1.1 Amine Alkaloids

3

OH

O HO O

H N

NH2

N H

O

O

8 Convolutamine I Type: Polyamines. C14H21Br3N2O Source: Bryozoan Amathia tortuosa (Bass Strait, Tasmania, Australia). Pharm: Cytotoxic (HEK-293); antitrypanosomal (Trypanosoma brucei brucei). Ref: R. A. Davis, et al, BoMC, 2011, 19, 6615 O

N Br

Br

N H Br

9 Crambescidin 816 Type: Polyamines. C45H80N6O7 Oil, [α]D25 = −20.4° (c = 0.4, MeOH). Source: Sponges Crambe crambe and Batzella sp. Pharm: Cytotoxic (cortical neurons, almost complete cell death at 1 μmol/L (86.3 ± 6.8)%); cytotoxic (L1210, 0.1 μg/mL, cell growth inhibition 98%); antiviral (HSV-1, 1.25 μg/well, complete inhibition with diffuse cytotoxicity); Ca2+ antagonist; ichthyotoxin. Ref: E. A. Jares-Erijman, et al, JOC, 1991, 56, 5712; 1993, 58, 4805│ R. G. S. Berlinck, et al, JNP, 1993, 56, 1007│ S. G. Bondu, et al, RSC Advances, 2012, 2, 2828

H N

O

N

OH

O

NH2

N

O

N 14

H

OH O

NH2

O

10 Didemnidine A Type: Polyamines. C17H26N4O22+ Brown oil. Source: Ascidian Didemnum sp. (Tiwai Pt., Southland, New Zealand). Pharm: Antitrypanosomal (Trypanosoma brucei rhodesience, IC50 = 59 μmol/L, control Melarsoprol, IC50 = 0.01 μmol/L; Trypanosoma cruzi, IC50 = 130 μmol/L, control Benznidazole, IC50 = 1.35 μmol/L); antileishmanial (Leishmania donovani, IC50 > 180 μmol/L, control Miltefosine, IC50 = 0.52 μmol/L); antiplasmodial (Plasmodium falciparum K1, IC50 = 41 μmol/L,

4

1 Amine Guanidine and Amide Alkaloids

control Chloroquine, IC50 = 0.20 μmol/L); cytotoxic (L-6 rat skeletal myoblast cell line, IC50 = 24 μmol/L, control Podophyllotoxin, IC50 = 0.01 μmol/L). Ref: R. Finlayson, et al, JNP, 2011, 74, 888 O

O

N H H

N H

H

N

+

H H

H N

+

11 Didemnidine B Type: Polyamines. C17H25BrN4O22+ Brown oil. Source: Ascidian Didemnum sp. (Tiwai Pt., Southland, New Zealand). Pharm: Antitrypanosomal (Trypanosoma brucei rhodesience, IC50 = 44 μmol/L, control Melarsoprol, IC50 = 0.01 μmol/L; Trypanosoma cruzi, IC50 = 82 μmol/L, control Benznidazole, IC50 = 1.35 μmol/L); antileishmanial (Leishmania donovani, IC50 > 160 μmol/L, control Miltefosine, IC50 = 0.52 μmol/L); antiplasmodial (Plasmodium falciparum K1, IC50 = 15 μmol/L, control Chloroquine, IC50 = 0.20 μmol/L); cytotoxic (L-6 rat skeletal myoblast cell line, IC50 = 25 μmol/L, control Podophyllotoxin, IC50 = 0.01 μmol/L). Ref: R. Finlayson, et al, JNP, 2011, 74, 888 O

O N H

Br

N H

H H

N

+

H H

H N

+

12 Estatin A Type: Polyamines. C18H25N5O5 Needles + 1H2O, mp 223–225 °C (dec), [α]D24 = +41.8° (c = 0.6, H2O). Source: Marine-derived fungus Microascus longirostris from an unidentified sponge. Pharm: Proteases inhibitors (Cysteine proteases: Cathepsin L, IC50 = 0.004 μg/mL; Cathepsin B, IC50 = 0.270 μg/mL; Papain, IC50 = 0.130 μg/mL; Ficin, IC50 = 0.032 μg/mL; Bromelain, IC50 = 0.600 μg/mL; Serine proteases: Trypsin, IC50 > 100 μg/mL; Chymostatin, IC50 > 100 μg/mL; Metal protease: Thermolysin, IC50 > 100 μg/mL; Aspartic protease: Cathepsin D, IC50 > 100 μg/mL). Ref: J. -T. Woo, et al, Biosci., Biotechnol., Biochem., 1995, 59, 350

1.1 Amine Alkaloids

O

O

O

H N

HO

H N

N H

O

5

NH2 NH

13 Estatin B Type: Polyamines. C18H25N5O6 Needles + 1H2O, mp 217–218 °C (dec), [α]D24 = +46.8° (c = 0.2, 0.1 M HCl). Source: Marine-derived fungus Microascus longirostris from an unidentified sponge. Pharm: Proteases inhibitors (Cysteine proteases: Cathepsin L, IC50 = 0.006 μg/mL; Cathepsin B, IC50 = 0.320 μg/mL; Papain, IC50 = 0.180 μg/mL; Ficin, IC50 = 0.038 μg/mL; Bromelain, IC50 = 0.260 μg/mL; Serine proteases: Trypsin, IC50 > 100 μg/mL; Chymostatin, IC50 > 100 μg/mL; Metal protease: Thermolysin, IC50 > 100 μg/mL; Aspartic protease: Cathepsin D, IC50 > 100 μg/mL). Ref: J. -T. Woo, et al, Biosci., Biotechnol., Biochem., 1995, 59, 350 O

O

O

H N

HO

H N

N H

O

NH2 NH

OH

14 Eusynstyelamide A Eusynstyelamide Type: Polyamines. C32H40Br2N10O4 Source: Ascidian Eusynstyela misakiensis, ascidian Eusynstyela latericius (Great Barrier Reef). Pharm: Inhibitor of neuronal nitric oxide synthase (nNOS) (IC50 = 41.7 μmol/L); inhibitor of pyruvate phosphate dikinase (PPDK) (IC50 = 19 mmol/L). Ref: J. C. Swersey, et al, JNP, 1994, 57, 842 (Eusynstyelamide)│ D. M. Tapiolas, et al, JNP, 2009, 72, 1115│ M. Tadesse, et al, JNP, 2011, 74, 837 NH2

H N O

NH

HO 3

Br H

N OH H N 5

O

N H NH Br

NH HN

NH2

6

1 Amine Guanidine and Amide Alkaloids

15 Eusynstyelamide B Type: Polyamines. C32H40Br2N10O4 Pale yellow oil. Source: Ascidian Eusynstyela latericius, ascidian Eusynstyela latericius (Great Barrier Reef). Pharm: Inhibitor of neuronal nitric oxide synthase (nNOS) (IC50 = 4.3 μmol/L); inhibitor of pyruvate phosphate dikinase (PPDK) (IC50 = 20 mmol/L); cytotoxic (MDA-MB-231, potent cell cycle inhibitor); inhibits proliferation of LNCaP cells (G2 phase); topoisomerase II inhibitor (in LNCaP cells); antibacterial (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Corynebacterium glutamicum, and MRSA, for Eusynstyelamide B, D, E and F, IC50 between 6.25 μmol/L and >50 μmol/L). Ref: D. M. Tapiolas, et al, JNP, 2009, 72, 1115│ M. Tadesse, et al, JNP, 2011, 74, 837│ M. Liberio, et al, Eur. J. Cancer, 2013, 49 (Suppl. 2), S177│ M. Liberio, et al, Mar. Drugs, 2014, 12, 5222 NH2

H N O

NH

HO 3

Br

N OH H N 5

H

O

N H NH

NH

Br

HN

NH2

16 ent-Eusynstyelamide B Type: Polyamines. C32H40Br2N10O4 Source: Bryozoan Tegella cf. spitzbergensis (Bear I., North Atlantic). Pharm: Antibacterial (Staphylococcus aureus); antifungal (Candida albicans, modest). Ref: M. Tadesse, et al, JNP, 2011, 74, 837 NH2

H N O HO

NH N

Br

OH H N

H

O

N H NH Br

NH HN

NH2

1.1 Amine Alkaloids

7

17 Eusynstyelamide C Type: Polyamines. C32H40Br2N10O4 Pale yellow oil, [α]D19 = +17° (c = 0.1, MeOH). Source: Ascidian Eusynstyela latericius, ascidian Eusynstyela latericius (Great Barrier Reef). Pharm: Inhibitor of neuronal nitric oxide synthase (nNOS) (IC50 = 5.8 μmol/L). Ref: D. M. Tapiolas, et al, JNP, 2009, 72, 1115 NH2

H N O

NH

HO 3

Br

N OH H N 5

H

O

N H NH

NH

Br

HN

NH2

18 Eusynstyelamide D Type: Polyamines. C30H36Br2N6O4 Source: Arctic bryozoan Tegella cf. spitzbergensis (Bear I., North Atlantic). Pharm: Antibacterial (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Corynebacterium glutamicum, and MRSA, for Eusynstyelamide B, D, E and F, IC50 between 6.25 μmol/L and >50 μmol/L); cytotoxic (melanoma cell line A2058). Ref: M. Tadesse, et al, JNP, 2011, 74, 837

NH2 O HO

N

Br

OH H N

H O

N H NH

NH2

Br

19 Eusynstyelamide E Type: Polyamines. C30H38Br2N8O4 Source: Arctic bryozoan Tegella cf. spitzbergensis (Bear I., North Atlantic). Pharm: Antibacterial (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Corynebacterium glutamicum, and MRSA, for Eusynstyelamide B, D, E and F, IC50 between 6.25 μmol/L and >50 μmol/L);cytotoxic

8

1 Amine Guanidine and Amide Alkaloids

(A2058); antifungal (Candida albicans, modest). Ref: M. Tadesse, et al, JNP, 2011, 74, 837 NH2

H N O

NH

HO

N

Br

OH H N

H

O

N H NH

NH2

Br

20 Eusynstyelamide F Type: Polyamines. C30H38Br2N8O4 Source: Arctic bryozoan Tegella cf. spitzbergensis (arctic, Bear I., North Atlantic). Pharm: Antibacterial (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Corynebacterium glutamicum, and MRSA, for Eusynstyelamide B, D, E and F, IC50 between 6.25 μmol/L and > 50 μmol/L); Ref: M. Tadesse, et al, JNP, 2011, 74, 837 NH2 O HO

N OH H N

Br H

O

N H NH Br

NH HN

NH2

21 Fromia monilis Alkaloid Type: Polyamines. C23H49N3O3 [α]D = +3.5°. Source: Starfishes Fromia monilis and Celerina heffernani (New Caledonia). Pharm: Anti-HIV-1 (cells CEM 4 infacted by HIV-1, CC50 = 2.7 μg/mL). Ref: E. Palagoano, et al, Tetrahedron, 1995, 51, 3675 OH NH2 HO

N

13

O

NH2

1.1 Amine Alkaloids

9

22 Ianthelliformisamine A Type: Polyamines. C20H32Br2N4O2 Source: Sponge Suberea ianthelliformis (Manta Ray Bommie, Stradbroke Is., Australia). Pharm: Antibacterial (Pseudomonas aeruginosa, selective). Ref: M. Xu, et al, JNP, 2012, 75, 1001 Br O

HN H N

Br

N H

NH2

O

23 Ianthelliformisamine B Type: Polyamines. C17H25Br2N3O2 Source: Sponge Suberea ianthelliformis (Manta Ray Bommie, Stradbroke Is., Australia). Pharm: Antibacterial (Pseudomonas aeruginosa, selective). Ref: M. Xu, et al, JNP, 2012, 75, 1001 Br O

HN NH2

H N Br O

24 Ianthelliformisamine C Type: Polyamines. C30H38Br4N4O4 Source: Sponge Suberea ianthelliformis (Manta Ray Bommie, Stradbroke Is., Australia). Pharm: Antibacterial (Pseudomonas aeruginosa, selective). Ref: M. Xu, et al, JNP, 2012, 75, 1001 Br

O

O

HN H N

Br O

N H

Br

N H

O Br

25 Lipogrammistin A Type: Polyamines. C35H66N4O3 Exists in solution as a mixture of 4 conformers, [α]D = +18.5° (c = 0.86, MeOH). Source: Soapfish Diploprion bifasciatum (secreted mucus, Japan). Pharm: Ichthyotoxin; LD (medaka cells Oryzias latipes) = 10 ppm (time-to-death 50 min), (mus ip) = 100 mg/kg (time-to-death 14 min); cytolytic (rbt erythrocytes, fertilized sea urchin eggs, 10 μg/mL). Ref: H. Onuki, et al, Tet. Lett., 1993, 34, 5609│ H. Onuki, et al, JOC, 1998, 63, 3925│ A. Fujiwara, et al, Synlett, 2000, 11, 1667

10

1 Amine Guanidine and Amide Alkaloids

H N NH

O O

N N O

26 Monodontamide A Type: Polyamines. C25H30N4O5 Amorph. solid. Source: Prosobranch Monodonta labio (Japan). Pharm: Serine protease inhibitor (weak). Ref: H. Niwa, et al, Tet. Lett., 1993, 34, 7441│ H. Niwa, et al, Tetrahedron, 1994, 50, 6805 O

H N

H N

N H

O

O

O

HN O

27 Monodontamide B Type: Polyamines. C26H32N4O7 Amorph. solid. Source: Prosobranch Monodonta labio (Japan). Pharm: Serine protease inhibitor (weak). Ref: H. Niwa, et al, Tet. Lett., 1993, 34, 7441│ H. Niwa, et al, Tetrahedron, 1994, 50, 6805 HO 22 21

O

O

N H

H N

H N O

O

O

H

N O

28 Monodontamide C Type: Polyamines. C25H32N4O6 Amorph. solid. Source: Prosobranch Monodonta labio (Japan). Pharm: Serine protease inhibitor (weak). Ref: H. Niwa, et al, Tet. Lett., 1993, 34, 7441│ H. Niwa, et al, Tetrahedron, 1994, 50, 6805 HO O

O N H

H N

H N O

O

O

NH2

1.1 Amine Alkaloids

11

29 Monodontamide D Type: Polyamines. C27H31N5O5 Amorph. solid. Source: Prosobranch Monodonta labio (Japan). Pharm: Serine protease inhibitor (weak). Ref: H. Niwa, et al, Tetrahedron, 1994, 50, 6805 H N

O

H N

H N

N H

O

O

O

HN O

30 Monodontamide E Type: Polyamines. C26H31N5O4 Amorph. solid. Source: Prosobranch Monodonta labio (Japan). Pharm: Serine protease inhibitor (weak). Ref: H. Niwa, et al, Tetrahedron, 1994, 50, 6805 H N

O

H N

H N

N H

O

O

O

NH2

31 Motuporamine A Type: Polyamines. C18H39N3 Oil (di-Ac). Source: Sponge Xestospongia exigua (Papua New Guinea). Pharm: Cytotoxic (hmn solid carcinoma cell lines in vitro, IC50 = 0.6 μg/mL). Ref: D. E. Williams, et al, JOC, 1998, 63, 4838│ J. E. Baldwin, et al, Tetahedron Lett., 1999, 40, 5401│ W. P. D. Goldring, et al, Org. Lett., 1999, 1, 1471

H 2N

N H

N

6

32 Motuporamine B Type: Polyamines. C19H41N3 Oil (di-Ac). Source: Sponge Xestospongia exigua (Papua New Guinea). Pharm: Cytotoxic (hmn solid carcinoma cell lines in vitro, IC50 = 0.6 μg/mL). Ref: D. E. Williams, et al, JOC, 1998, 63, 4838│ J. E. Baldwin, et al, Tetahedron Lett., 1999, 40, 5401│ W. P. D. Goldring, et al, Org. Lett., 1999, 1, 1471

H 2N

N H

N

7

12

1 Amine Guanidine and Amide Alkaloids

33 Motuporamine C Type: Polyamines. C20H41N3 Source: Sponge Xestospongia exigua (Papua New Guinea). Pharm: Cytotoxic (hmn solid carcinoma cell lines in vitro, IC50 = 0.6 μg/mL). Ref: D. E. Williams, et al, JOC, 1998, 63, 4838 NH2 N N H

34 Nigribactin Type: Polyamines. C30H32N4O9 Source: Marine-derived bacterium Vibrio nigripulchritudo (global marine Galathea 3 expedition). Pharm: Modulator of Staphylococcus aureus virulence gene expression. Ref: A. Nielsen, et al, Mar. Drugs, 2012, 10, 2584

HO N O

O H N

HO OH

H N

N 3

OH

3

O

O

OH

35 Oceanapia Bromotyrosine alkaloid Type: Polyamines. C17H26Br2N6O3 Source: Sponge Oceanapia sp. Pharm: Mycothiol S-conjugate amidase inhibitor. Ref: G. M. Nicholas, et al, Org. Lett., 2001, 3, 1543 NH2 Br O

N

OH H N

Br O

NH N H

NH2

36 Phidianidine A Type: Polyamines. C17H22BrN7O Source: Nudibranch Phidiana militaris (Hainan I., South China Sea). Pharm: Cytotoxic (C6, IC50 = (0.642 ± 0.2)μmol/L; HeLa, IC50 = (1.52 ± 0.3)μmol/L; CaCo-2, IC50 = (35.5 ± 4)μmol/L; H9c2, IC50 = (2.26 ± 0.6)μmol/L;

1.1 Amine Alkaloids

13

3T3-L1, IC50 = (0.14 ± 0.2)μmol/L); chemokine receptor (CXCR4) ligand; inhibitor of CXCL12 (C-X-C motif chemokine 12)-induced DNA synthesis; inhibitor of cell migration; inhibitor of extracellular-signal-regulated kinases (ERK1/2) activation; inhibitor of dopamine transporter (DAT); μ-opioid receptor ligand (selective and potent); neuroprotective agent (against Aβ25–35-, H2O2- and OGD (oxygen-glucose deprivation)-induced neurotoxicity in SH-SY5Y cells). Ref: M. Carbone, et al, Org. Lett., 2011, 13, 2516│ R. M. Vitale, et al, ACS Chem. Biol., 2013, 8, 2762│ J. T. Brogan, et al, ACS Chem. Neurosci., 2012, 3, 658│ C. -S. Jiang, et al, BoMCL, 2015, 25, 216

O

H N

H N

N

NH2

5

NH

N

Br N H

37 Phidianidine B Type: Polyamines. C17H23N7O Source: Nudibranch Phidiana militaris (Hainan I., South China Sea). Pharm: Cytotoxic (C6, IC50 = (0.98 ± 0.3)μmol/L; HeLa, IC50 = (0.417 ± 0.4)μmol/L; CaCo-2, IC50 = (100.2 ± 8.5)μmol/L; H9c2, IC50 = (5.42 ± 0.8)μmol/L; 3T3-L1, IC50 = (0.786 ± 0.3)μmol/L); inhibitor of dopamine transporter (DAT); μ-opioid receptor ligand (selective and potent); neuroprotective agent (against Aβ25–35-, H2O2- and OGD (oxygen-glucose deprivation)-induced neurotoxicity in SH-SY5Y cells). Ref: M. Carbone, et al, Org. Lett., 2011, 13, 2516│ J. T. Brogan, et al, ACS Chem. Neurosci., 2012, 3, 658│ C. -S. Jiang, et al, BoMCL, 2015, 25, 216

N O N

H N

H N

NH2

5

NH

N H

38 Pseudoceramine B Type: Polyamines. C33H48Br4N6O5 Source: Sponge Pseudoceratina sp. (Erskine I., Great Barrier Reef). Pharm: Inhibits secretion of virulence factor Yersinia Outer Protein E. Ref: S. Yin, et al, Org. Biomol. Chem., 2011, 9, 6755

14

1 Amine Guanidine and Amide Alkaloids

Br O

NH

H N

Br

N

N

O

HN Br O O

N

HO Br

39 Pseudoceratidine Type: Polyamines. C17H21Br4N5O2 Solid, mp 62–65 °C. Source: Sponges Pseudoceratina crassa and Pseudoceratina purpurea. Pharm: Antifoulant (barnacle Balanus amphitrite, inhibits larval settlement and metamorphosis, ED50 = 8.0 μg/mL); antimicrobial. Ref: S. Tsukamoto, et al, Tet. Lett., 1996, 37, 1439│ J. A. Ponasik, et al, Tet. Lett., 1996, 37, 6041│ J. A. Ponasik, et al, Tetrahedron, 1998, 54, 6977 Br O H N

H N Br

N H

Br

N H

N H

O Br

40 Rexostatine Type: Polyamines. C15H27N5O5 Needles (Me2CO aq), [α]D25 = +24.4° (c = 1, 0.1M HCl). Source: Marine-derived fungus Microascus longirostris from an unidentified sponge. Pharm: Proteases inhibitors (Cysteine proteases: Cathepsin L, IC50 = 0.050 μg/mL; Cathepsin B, IC50 = 0.018 μg/mL; Papain, IC50 = 0.036 μg/ mL; Ficin, IC50 = 0.023 μg/mL; Bromelain, IC50 = 0.103 μg/mL; Serine proteases: Trypsin, IC50 > 100 μg/mL; Chymostatin, IC50 > 100 μg/mL; Metal protease: Thermolysin, IC50 > 100 μg/mL; Aspartic protease: Cathepsin D, IC50 > 100 μg/mL). Ref: J. -T. Woo, et al, Biosci., Biotechnol., Biochem., 1995, 59, 350 O

O

O H N

HO O

H N

NH2

N H NH

1.1 Amine Alkaloids

15

41 Rhapsamine Type: Polyamines. C34H60N4O2 Amorph. solid, [α]D = 0° (c = 0.006, MeOH). Source: Calcareous sponge Leucetta leptorhaphis (Antarctic). Pharm: Cytotoxic (KB, LC50 = 1.8 μg/mL). Ref: G. S. Jayatilake, et al, Tet. Lett., 1997, 38, 7507 OH

H N

NH2

NH2 N H

OH

42 Sinulamide Type: Polyamines. C34H66N4O2+ Powder (hydrochloride). Source: Soft coral Sinularia sp. (Japan). Pharm: HK-ATPase inhibitor (IC50 = 5.5 μmol/L, potential antiulcer drug, HK-ATPase is a gastric proton pump of stomach and is the enzyme primarily responsible for the acidification of the stomach contents); cytotoxic (L1210, IC50 = 3.1 μg/mL, P388, IC50 = 4.5 μg/mL). Ref: N. U. Sata, et al, Tet. Lett., 1999, 40, 719

3

O

N H

3

N

+

N 3

+

NH2 3

43 Symphyocladin G Type: Polyamines. C15H10Br6N2O5 Source: Red alga Symphyocladia latiuscula (Qingdao, Shandong Province, China). Pharm: Antifungal (modest). Ref: X. Xu, et al, Tet. Lett., 2012, 53, 2103 Br

Br

O

OH

HO N H Br

HO Br

N H OH

Br Br

44 Tenacibactin A Type: Polyamines. C15H28N2O5 Powder. Source: Marine-derived bacterium Tenacibaculum sp. A4K-17. Pharm: Siderophore. Ref: J. -H. Jang, et al, JNP, 2007, 70, 563

16

1 Amine Guanidine and Amide Alkaloids

O

OH H N

N

O O

O

45 Tenacibactin B Type: Polyamines. C14H26N2O5 Powder. Source: Marine-derived bacterium Tenacibaculum sp. A4K-17. Pharm: Siderophore. Ref: J. -H. Jang, et al, JNP, 2007, 70, 563 O

OH

H N

N

OH O

O

46 Tenacibactin C Type: Polyamines. C23H42N4O8 Powder. Source: Marine-derived bacterium Tenacibaculum sp. A4K-17. Pharm: Fe-chelating activity (IC50 = 110–115 μmol/L); siderophore. Ref: J. -H. Jang, et al, JNP, 2007, 70, 563 O

O

O N H

N

N

OH O

OH

H N

HO O

47 Tenacibactin D Type: Polyamines. C28H54N6O8 Powder. Source: Marine-derived bacterium Tenacibaculum sp. A4K-17. Pharm: Fe-chelating activity (IC50 = 110–115 μmol/L); siderophore. Ref: J. -H. Jang, et al, JNP, 2007, 70, 563 O

O N H

N OH O H 2N

H N

N OH

O

O N

OH

1.1 Amine Alkaloids

17

48 Tokaradine C Type: Polyamines. C17H25Br2N3O2 Amorph. yellow solid. Source: Sponge Pseudoceratina purpurea (Southern Japan). Pharm: Toxic (crab Hemigrapsus sanguineus). Ref: N. Fusetani, et al, Tetrahedron, 2001, 57, 7507 Br O H N

Br

N H

O

NH2

49 N′,N ′′,N ′′-Trimethyl-N- (3-methyl-2Z,4E-dodecadienoyl)spermidine Type: Polyamines. C23H45N3O Pale yellow oil (rapidly darkens on standing). Source: Soft coral Sinularia sp. Pharm: Antimicrobial (in vivo). Ref: R. Kazlauskas, et al, Aust. J. Chem., 1982, 35, 69│ D. J. Faulkner, Nat. Prod. Rep., 1984, 1, 551 O N H

N

N

50 N′,N′,N′-Trimethyl-N- (3-methyl-2,4-dodecadienoyl)spermidine Type: Polyamines. C23H45N3O Source: Soft coral Sinularia sp. (Nauru, Oceania, most likely Sinularia compacya). Pharm: Cytotoxic. Ref: Y. -H. Choi, et al, JNP, 1997, 60, 495

O Z/E

N

N

N H

51 N′,N′,N′-Trimethyl-N- (3-methyldodecanoyl)spermidine Type: Polyamines. C23H49N3O Source: Soft corals Sinularia sp. (Nauru, Oceania, most likely Sinularia compacya) and Sinularia brongersmai. Pharm: Cytotoxic (P388, ED50 = 0.04 μg/mL); cytotoxic (hmn tumor cell lines, IC50 = 17 ng/mL; induction of apoptotic phenomena). Ref: F. J. Schmitz, et al, Tet. Lett., 1979, 3387│ Y. -H. Choi, et al, JNP, 1997, 60, 495│ M. Ojika, et al, Biosci., Biotechnol., Biochem., 2003, 67, 1410 O N H

N

N

18

1 Amine Guanidine and Amide Alkaloids

52 N′,N′′,N′′-Trimethyl-N- (3-methyl-2Z-dodecenoyl)spermidine Type: Polyamines. C23H47N3O Pale yellow oil. Source: Soft coral Sinularia sp. (Nauru, Oceania, most likely Sinularia compacya). Pharm: Cytotoxic (hmn tumor cell lines, IC50 = 17 ng/mL; induction of apoptotic phenomena). Ref: R. Kazlauskas, et al, Aust. J. Chem., 1982, 35, 69│ Y. -H. Choi, et al, JNP, 1997, 60, 495│ M. Ojika, et al, Biosci., Biotechnol., Biochem., 2003, 67, 1410

O

H N

N

N

4' 2'

53 N′,N′,N′-Trimethyl-N- (3-methyl-2E-dodecenoyl)spermidine Type: Polyamines. C23H47N3O Source: Soft corals Sinularia sp. (Nauru, Oceania, most likely Sinularia compacya) and Sinularia brongersmai. Pharm: Cytotoxic (P388, ED50 = 0.04 μg/mL); cytotoxic (hmn tumor cell lines, IC50 = 17 ng/mL; induction of apoptotic phenomena). Ref: F. J. Schmitz, et al, Tet. Lett., 1979, 3387│ Y. -H. Choi, et al, JNP, 1997, 60, 495│ M. Ojika, et al, Biosci., Biotechnol., Biochem., 2003, 67, 1410 O N 6

N

N H

54 N′,N′′,N′′-Trimethyl-N- (5-methyl-3-tetradecenoyl)spermidine Type: Polyamines. C25H51N3O Oil, [α]D = +7° (c = 0.2, CH2Cl2). Source: Soft coral Sinularia sp. (Nauru, Oceania, most likely Sinularia compacya). Pharm: Cytotoxic (P388, ED50 = 0.04 μg/mL). Ref: Y. -H. Choi, et al, JNP, 1997, 60, 495 O 7

N H

N

N

1.2 Guanidine Alkaloids 55 Aplicyanin B Type: Guanidine alkaloids. C14H15BrN4O Pale yellow oil, [α]D25 = +8.7° (c = 0.1, CHCl3). Source: Ascidian Aplidium cyaneum (Antarctica). Pharm: Cytotoxic (A549, GI50 = 0.66 μmol/L, HT29, GI50 = 0.39 μmol/L, MDA-MB-231, GI50 = 0.42 μmol/L),

1.2 Guanidine Alkaloids

19

antimitotic (HeLa, mitotic ratio of cell culture was determined using a specific microplate immunoassay ELISA, IC50 = 1.19 μmol/L). Ref: F. Reyes, et al, Tetrahedron, 2008, 64, 5119│ M. Šíša, et al, JMC, 2009, 52, 6217 H N

N

2'

O

HN

Br N H

56 Aplicyanin D Type: Guanidine alkaloids. C15H17BrN4O2 Pale yellow oil, [α]D25 = +9.5° (c = 0.1, CHCl3). Source: Ascidian Aplidium cyaneum (Antarctica). Pharm: Cytotoxic (A549, GI50 = 0.63 μmol/L, HT29, GI50 = 0.33 μmol/L, MDA-MB-231, GI50 = 0.41 μmol/L), antimitotic (HeLa, mitotic ratio of cell culture was determined using a specific microplate immunoassay ELISA, IC50 = 1.09 μmol/L). Ref: F. Reyes, et al, Tetrahedron, 2008, 64, 5119│ M. Šíša, et al, JMC, 2009, 52, 6217 H N

N O

HN

Br N O

57 Aplicyanin E Type: Guanidine alkaloids. C13H14Br2N4O Pale yellow oil, [α]D25 = +0.5° (c = 0.1, CHCl3). Source: Ascidian Aplidium cyaneum (Antarctica). Pharm: Cytotoxic (A549, GI50 = 8.70 μmol/L, HT29, GI50 = 7.96 μmol/L, MDA-MB-231, GI50 = 7.96 μmol/L), antimitotic (HeLa, mitotic ratio of cell culture was determined using a specific microplate immunoassay ELISA, mild). Ref: F. Reyes, et al, Tetrahedron, 2008, 64, 5119│ M. Šíša, et al, JMC, 2009, 52, 6217 H N

HN HN Br Br

N O

20

1 Amine Guanidine and Amide Alkaloids

58 Aplicyanin F Type: Guanidine alkaloids. C15H16Br2N4O2 Pale yellow oil, [α]D25 = +1.9° (c = 0.1, CHCl3). Source: Ascidian Aplidium cyaneum (Antarctica). Pharm: Cytotoxic (A549, GI50 = 1.31 μmol/L, HT29, GI50 = 0.47 μmol/L, MDA-MB-231, GI50 = 0.81 μmol/L), antimitotic (HeLa, mitotic ratio of cell culture was determined using a specific microplate immunoassay ELISA, IC50 = 0.18–0.036 μmol/L). Ref: F. Reyes, et al, Tetrahedron, 2008, 64, 5119│ M. Šíša, et al, JMC, 2009, 52, 6217 H N

N O

HN

Br N

Br

O

59 (+)-7-Bromotrypargine Type: Guanidine alkaloids. C15H20BrN5 Brown gum (bistrifluoroacetate salt), [α]D22 = +20° (c = 0.02, MeOH) (bistrifluoroacetae). Source: Sponge Ancorina sp. (Waterfall Bay, Tasmania, Australia). Pharm: Antiplasmodial (Plasmodium falciparum Dd2 and 3D7 strain, IC50 = 3.5–5.4 μmol/L). Ref: R. A. Davis, et al, Tet. Lett., 2010, 51, 583

Br

7

NH

N H

NH NH2

N H

60 Cypridina Luciferin Type: Guanidine alkaloids. C22H27N7O Cryst. (MeOH) (dihydrobromide), mp 252–254 °C (dec) (dihydrobromide). Source: Crustacean Cypridina hilgendorfii. Pharm: Bioluminescent substance. Ref: Y. Kishi, et al, Tet. Lett., 1966, 3437│ H. Nakamura, et al, Tet. Lett., 2000, 41, 2185

O N N H N H

N H N

NH2 NH

1.2 Guanidine Alkaloids

21

61 3’-Deoxytubastrine Type: Guanidine alkaloids. C9H12N3O1+ Oil (monohydrochloride trihydrate). Source: Sponge Spongosorites sp. (Australia). Pharm: Antimicrobial. Ref: S. Urban, et al, Aust. J. Chem., 1994, 47, 2279 H N

NH2

H

HO

N

+

H

62 Fuscusine Type: Guanidine alkaloids. C13H20N4O2 Oil. Source: Starfish Perknaster fuscus antarcticus (Antarctic, body walls). Pharm: Ichthyotoxin (most ichthyotoxic of Antarctic). Ref: F. Kong, et al, Nat. Prod. Lett., 1992, 1, 71 HO NH

NH

OH

N H

NH2

63 Monanchomycalin C Type: Guanidine alkaloids. C47H85N6O51+ Source: Sponge Monanchora pulchra (two dredged samples, Kuril Is., Russia). Pharm: Cytotoxic (MDA-MB-231, modest). Ref: K. M. Tabakmakher, et al, Nat. Prod. Commun., 2013, 8, 1399

H O N

O H N

NH2

N+

O H

N 14

O

NH2

O

64 Nagelamide U Type: Guanidine alkaloids. C13H18Br2N6O5S Colorless amorphous solid, [α]D21 = −32.0° (c = 0.025, MeOH). Source: Sponge Agelas sp. (Kerama I., Okinawa). Pharm: Antifungal (Candida albicans, IC50 = 4 μg/mL). Ref: N. Tanaka, et al, Tet. Lett., 2013, 54, 3794

22

1 Amine Guanidine and Amide Alkaloids

H N

+

H

H2 N H

Br

O

H N

Br N H

NH

O

N S

O

O O

65 (E)-Narain Type: Guanidine alkaloids. C11H17N3O6S Source: Sponge Jaspis sp. (Japan). Pharm: Induces metamorphosis in ascidian larvae. Ref: S. Ohta, et al, Tet. Lett., 1994, 35, 4579│ S. Tsukamoto, et al, Tet. Lett., 1994, 35, 1752│ S. Ohta, et al, Biosci. Biotech. Biochem., 1994, 58, 1752 O O

HO

NH2 O N S H

N

O

HO

66 (Z)-Narain Type: Guanidine alkaloids. C11H17N3O6S Source: Sponge Jaspis sp. (Japan). Pharm: Induces metamorphosis in ascidian larvae. Ref: S. Ohta, et al, Tet. Lett., 1994, 35, 4579│ S. Tsukamoto, et al, Tet. Lett., 1994, 35, 1752│ S. Ohta, et al, Biosci. Biotech. Biochem., 1994, 58, 1752 HO

HO

O O

S O N H

O NH2 N

67 Pulchranin A Type: Guanidine alkaloids. C14H29N3O Source: Sponge Monanchora pulchra (two dredged samples, Kuril Is., Russia (Makarieva, 2013), sponge Monanchora pulchra (depth of 175 m, August 2008, Urup I., Southern Okhotsk Sea, Russia, yield = 0.02% dw) (Guzii, 2013). Pharm: TRPV1 inhibitor (a transient receptor potential cationic channel of subfamily V, EC50 = 41.2 μmol/L) (Guzii, 2013); TRPV1 inhibitor (EC50 = (27.5 ± 1.4)μmol/L); TRPV3 inhibitor (EC50 = (71.8 ± 9.4)μmol/L); TRPA1

1.2 Guanidine Alkaloids

23

inhibitor (EC50 = (174.2 ± 7.4)μmol/L). Ref: A. G. Guzii, et al, Tet. Lett., 2013, 54, 1247│ T. N. Makarieva, et al, Nat. Prod. Commun., 2013, 8, 1229 NH NH2

N H

5

OH

68 Pulchranin B Type: Guanidine alkaloids. C13H27N3O Source: Sponge Monanchora pulchra (two dredged samples, Kuril Is., Russia). Pharm: TRPV1 inhibitor (EC50 = (95.4 ± 13.1) μmol/L); TRPV3 inhibitor (EC50 = (117.9 ± 11.8)μmol/L); TRPA1 inhibitor (EC50 > 200 μmol/L). Ref: T. N. Makarieva, et al, Nat. Prod. Commun., 2013, 8, 1229 NH NH2

N H

4

OH

69 Pulchranin C Type: Guanidine alkaloids. C12H25N3O Source: Sponge Monanchora pulchra (two dredged samples, Kuril Is., Russia). Pharm: TRPV1 inhibitor (EC50 = (182.7 ± 27.0) μmol/L); TRPV3 inhibitor (EC50 > 200 μmol/L); TRPA1 inhibitor (EC50 > 200 μmol/L). Ref: T. N. Makarieva, et al, Nat. Prod. Commun., 2013, 8, 1229 NH N H

3

OH

NH2

70 Pyraxinine Type: Guanidine alkaloids. C6H8N4 Amorph. solid. Source: Sponge Cymbastela cantharella (New Caledonia). Pharm: Inhibits macrophagic NO synthase induced by LPS. Ref: A. Al Mourabit, et al, JNP, 1997, 60, 290 H N

NH2 NH

N

71 Tubastrine Type: Guanidine alkaloids. C9H11N3O2 Light yellow solid, mp 173–175 °C. Source: Stony coral Tubastraea aurea, ascidians Aplidium orthium and Dendrodoa grossularia. Pharm: Antiviral. Ref: R. Sakai, et al, Chem. Lett., 1987, 127

24

1 Amine Guanidine and Amide Alkaloids

H N

NH2 NH2

HO OH

72 Isoptilocaulin Type: Ptilocaulins. C15H25N3 Source: Sponge Ptilocaulis aff. spiculifer. Pharm: Cytotoxic (L1210, ID50 = 1.4 μg/mL); antibacterial (gram-positive bacteria: Streptococcus pyogenes, MIC = 25 μg/mL, Streptococcus pneumoniae, MIC = 100 μg/mL, Streptococcus faecalis, MIC > 100 μg/mL, Staphylococcus aureus, MIC = 100 μg/mL, Escherichia coil, MIC > 100 μg/mL). Ref: G. C. Harbour, et al, JACS, 1981, 103, 5604 H

H H H

N H

NH NH

73 Mirabilin B Type: Ptilocaulins. C15H23N3 Cryst., [α]D = +41.6° (c = 0.48, MeOH). Source: Sponges Arenochalina mirabilis, Batzella sp. and Monanchora unguifera. Pharm: Antifungal (Cryptococcus neoformans, IC50 = 7.0 μg/mL); antileishmanial (Leishmania donovani, IC50 = 17 μg/mL). Ref: R. A. Barrow, et al, Aust. J. Chem., 1996, 49, 767│ A. D. Patil, et al, JNP, 1997, 60, 704│ H. -M. Hua, et al, BoMC, 2004, 12, 6461 NH2 N

N

H

74 (+)-Ptilocaulin Type: Ptilocaulins. C15H25N3 Crystal (nitrate), mp 183–185 °C (nitrate), [α]D = +74.4° (MeOH). Source: Sponge Ptilocaulis aff. spiculifer. Pharm: Cytotoxic (L1210, ID50 = 0.39 μg/mL); antibacterial (gram-positive bacteria: Streptococcus pyogenes, MIC = 3.9 μg/mL, Streptococcus pneumoniae, MIC = 15.6 μg/mL, Streptococcus

1.2 Guanidine Alkaloids

25

faecalis, MIC = 62.5 μg/mL, Staphylococcus aureus, MIC = 62.5 μg/mL, Escherichia coil, MIC = 62.5 μg/mL). Ref: G. C. Harbour, et al, JACS, 1981, 103, 5604 NH HN

NH H

H

H

75 Batzelladine A Type: Triazaacenaphthylene alkaloids. C42H73N9O4 Amorph. powder, [α]D25 = +8.9° (c = 2.3, MeOH). Source: Sponge Batzella sp. (Caribbean). Pharm: Antiplasmodial (in vitro Plasmodium falciparum FcB1, IC50 = 0.3 μmol/L, HeLa, TC50 = 2.9 μmol/L, SI (TC50/IC50) = 9.7); Inhibits binding of HIVgp-120 to CD4. Ref: A. D. Patil, et al, JOC, 1995, 60, 1182│ B. B. Snider, et al, JOC, 1999, 62, 1707│ A. S. Franklin, et al, JOC, 1999, 64, 1512│ R. Laville, et al, JNP, 2009, 72, 1589 NH N

O

NH 8

H N

H 2N

H 3

O

H

O

N

24

32

N

O

H

25

N H

NH

7

76 Batzelladine B Type: Triazaacenaphthylene alkaloids. C40H67N9O4 Amorph. powder, [α]D25 = +44.3° (c = 3.7, MeOH). Source: Sponge Batzella sp. (Caribbean Sea). Pharm: HIVgp-120-hmn CD4 binding inhibitor; interleukin binding inhibitor. Ref: A. D. Patil, et al, JOC, 1995, 60, 1182│ A. S. Franklin, et al, JOC, 1999, 64, 1512 NH O N

H

NH O H

O

24 32

N

O H N

NH2 NH

H

25

N N H

26

1 Amine Guanidine and Amide Alkaloids

77 Batzelladine D Type: Triazaacenaphthylene alkaloids. C25H46N6O2 Amorph. powder, [α]D25 = −1.2° (c = 0.9, MeOH). Source: Sponge Batzella sp. (Caribbean Sea). Pharm: HIVgp-120hmn CD4 binding inhibitor; cytotoxic (Vero, IC50 = 0.5 μmol/L). Ref: D. Patil, et al, JOC, 1995, 60, 1182│ A. S. Franklin, et al, JOC, 1999, 64, 1512│ A. F. Cohen, et al, Org. Lett., 1999, 1, 2169 O

H N

H 2N

H

H

O

N

NH

N

N H

78 Batzelladine E Type: Triazaacenaphthylene alkaloids. C27H46N6O2 Gum, [α]D25 = +87.1° (c = 1.9, MeOH). Source: Sponge Batzella sp. (Bahamas). Pharm: HIVgp-120-hmn CD4 binding inhibitor. Ref: D. Patil, et al, JOC, 1995, 60, 1182│ B. B. Snider et al, Tet. Lett., 1998, 39, 5697 O H N

H 2N

O

NH

N N

N H

79 Batzelladine F Type: Triazaacenaphthylene alkaloids. C37H64N6O2 [α]D = +19.4° (c = 0.87, MeOH). Source: Sponge Monanchora arbuscula [Syn. Batzella arbuscula] (Caribbean Sea). Pharm: Active in p56lck (tyrosine kinase) -CD4 dissociation assay (micromolar concentration). Ref: A. D. Patil, et al, JOC, 1997, 62, 1814│ G. P. Black, et al, Tetrahedron, 1999, 55, 6547│ B. B. Snider, et al, JNP, 1999, 62, 1707

N N H

O N

N

O N

N H

80 Batzelladine L Type: Triazaacenaphthylene alkaloids. C39H68N6O2 Gum, [α]D = +5° (c = 0.1, MeOH). Source: Sponge Monanchora unguifera. Pharm: Antibacterial (Staphylococcus aureus and MRSA, MIC = 0.25–5.0 μg/mL); AIDS opportunistic infectious pathogens;

1.2 Guanidine Alkaloids

27

antiplasmodial (in vitro, Plasmodium falciparum FcB1, IC50 = 0.3 μmol/L, HeLa, TC50 < 0.1 μmol/L, SI (TC50/IC50) < 1). Ref: H. -M. Hua, et al, Tetrahedron, 2007, 63, 11179│ R. Laville, et al, JNP, 2009, 72, 1589 H

H

O

N

H

18

N

N

7

O

N

21

H

H

22

29

H

N

N H H

8

81 Batzelladine M Type: Triazaacenaphthylene alkaloids. C35H58N6O2 Gum, [α]D = +41.1° (c = 0.09, MeOH). Source: Sponge Monanchora unguifera. Pharm: Antibacterial (Staphylococcus aureus and MRSA, MIC = 0.25–5.0 μg/mL); AIDS opportunistic infectious pathogens. Ref: H. -M. Hua, et al, Tetrahedron, 2007, 63, 11179 H

H O N N H

H N

O

N

N

N H

82 Celeromycalin 36R-Hydroxy-ptilomycalin A Type: Triazaacenaphthylene alkaloids. C45H80N6O6 [α]D = –4.5°. Source: Starfishes Fromia monilis and Celerina heffernani (New Caledonia). Pharm: Anti-HIV-1 (cells CEM 4 infacted by HIV-1, CC50 = 0.32 μg/mL); cytotoxic (high active). Ref: E. A. Jares-Erijman, et al, JOC, 1991, 56, 5712│ E. Palagiano, et al, Tetrahedron, 1995, 51, 3675 O H 5

OH

N

NH2

36R

H

O N

N

O

43

N

O H

NH2 O

83 Clathriadic acid Type: Triazaacenaphthylene alkaloids. C18H28N3O21+ Oil, [α]D24 = +13° (c = 0.2, MeOH). Source: Sponge Clathria calla (Guadeloupe I. (Fr.)). Pharm: Cytotoxic (MDA-MB-231,

28

1 Amine Guanidine and Amide Alkaloids

GI50 = 13.5 μmol/L, TGI > 30 μmol/L, LC50 > 30 μmol/L; A549, GI50 > 30 μmol/L, TGI > 30 μmol/L, LC50 > 30 μmol/L; HT29, GI50 > 30 μmol/L, TGI > 30 μmol/L, LC50 > 30 μmol/L); antiplasmodial (in vitro Plasmodium falciparum FcB1, IC50 = 2.3 μmol/L). Ref: R. Laville, et al, JNP, 2009, 72, 1589 O H N

HO

+

N H

N

5

84 Crambescidin 800 13-Deoxycrambescidin 816 Type: Triazaacenaphthylene alkaloids. C45H80N6O6 Oil. Source: Sponges Crambe crambe and Batzella sp., starfishes Fromia monilis and Celerina heffernani (New Caledonia). Pharm: Anti-HIV-1 (cells CEM 4 infacted by HIV-1, CC50 = 0.11 μg/mL) (Palagiano, 1995); Antiviral (HSV-1, 1.25 μg/well, complete inhibition with diffuse cytotoxicity); cytotoxic (L1210, 0.1 μg/mL, cell growth inhibition 98%); Ca2+ antagonist; ichthyotoxin. Ref: E. A. Jares-Erijman,et al, JOC, 1991, 56, 5712; 1993, 58, 4805│ R. G. S. Berlinck, et al, JNP, 1993, 56, 1007│ E. Palagiano, et al, Tetrahedron, 1995, 51, 3675

H N

O

N N

OH

O

NH2

13

O

N

NH2

14

H

H

O

O

85 Crambescidin 826 Type: Triazaacenaphthylene alkaloids. C47H82N6O6 Glassy solid, [α]D20 = −7.7° (c = 0.09, MeOH). Source: Sponge Monanchora sp. Pharm: HIV-1 fusion inhibitor. Ref: L. C. Chang, et al, JNP, 2003, 66, 1490 NH2 H

H

N

N N O H

O O

17

NH2

O

N O

O

1.2 Guanidine Alkaloids

29

86 Crambescidin 830 Type: Triazaacenaphthylene alkaloids. C46H82N6O7 Oil. Source: Sponge Crambe crambe. Pharm: Antiviral; cytotoxic. Ref: E. A. Jares-Erijman, et al, JOC, 1991, 56, 5712 NH2 O

H

OH N

N O H

N

O

13

OH

16

O

N O

NH2

87 Crambescidin 844 Type: Triazaacenaphthylene alkaloids. C47H84N6O7 Oil, [α]D25 = –10.32° (c = 0.19, MeOH). Source: Sponge Crambe crambe. Pharm: Antiviral (HSV-1, 1.25 μg/well, complete inhibition with diffuse cytotoxicity); cytotoxic (L1210, 0.1 μg/mL, cell growth inhibition 98%). Ref: E. A. Jares-Erijman, et al, JOC, 1991, 56, 5712 NH2 OH

H

O

N N O H

N

OH

N

O

17

O O

NH2

88 Dihomodehydrobatzelladine C Type: Triazaacenaphthylene alkaloids. C29H51N6O21+ Oil, [α]D24 = +19° (c = 0.05, MeOH). Source: Sponge Monanchora arbuscula (Martinique, Caribbean Sea). Pharm: Cytotoxic (MDA-MB-231, GI50 = 6.1 μmol/L, TGI = 9.8 μmol/L, LC50 = 15.6 μmol/L; A549, GI50 = 4.7 μmol/L, TGI = 8.2 μmol/L, LC50 = 13.1 μmol/L; HT29, GI50 = 3.1 μmol/L, TGI = 5.1 μmol/ L, LC50 = 8.2 μmol/L); antiplasmodial (in vitro Plasmodium falciparum FcB1, IC50 = 4.5 μmol/L). Ref: R. Laville, et al, JNP, 2009, 72, 1589 O H

H N

H 2N

3

N

O

+

NH 4

N

N H

7

89 Dinorbatzelladine A Type: Triazaacenaphthylene alkaloids. C40H69N9O4 Oil. Source: Sponge Monanchora arbuscula (Martinique, Caribbean Sea). Pharm: Cytotoxic (MDA-MB

30

1 Amine Guanidine and Amide Alkaloids

-231, GI50 = 3.0 μmol/L, TGI = 3.8 μmol/L, LC50 = 4.6 μmol/L; A549, GI50 = 4.9 μmol/L, TGI = 5.1 μmol/L, LC50 = 5.4 μmol/L; HT29, GI50 = 1.9 μmol/L, TGI = 4.2 μmol/L, LC50 = 7.6 μmol/L); antiplasmodial (in vitro Plasmodium falciparum FcB1, IC50 = 0.9 μmol/L). Ref: R. Laville, et al, JNP, 2009, 72, 1589 NH N

O

NH 8

N

O

H N

H 2N

O

3

N

O

N H

NH

5

90 Dinordehydrobatzelladine B Type: Triazaacenaphthylene alkaloids. C38H62N9O41+ Oil, [α]D24 = +28° (c = 0.05, MeOH). Source: Sponge Monanchora arbuscula (Martinique, Caribbean Sea). Pharm: Cytotoxic (A549, GI50 = 7.9 μmol/L, TGI = 14 μmol/L, LC50 = 14 μmol/L; HT29, GI50 = 6.2 μmol/L, TGI = 14 μmol/L, LC50 = 14 μmol/L); antiplasmodial (in vitro Plasmodium falciparum FcB1, IC50 = 0.8 μmol/L). Ref: R. Laville, et al, JNP, 2009, 72, 1589 NH N

O

NH 6

H N

H 2N

O

3

H N

O N

O

+

N H

5

NH

91 Fromiamycalin Type: Triazaacenaphthylene alkaloids. C45H78N6O5 [α]D = −12° (hydrochloride). Source: Starfishes Fromia monilis and Celerina heffernani (New Caledonia). Pharm: Anti-HIV-1 (cells CEM 4 infacted by HIV-1, CC50 = 0.11 μg/mL); cytotoxic. Ref: E. A. Jares-Erijman, et al, JOC, 1991, 56, 5712│ E. Palagiano, et al, Tetrahedron, 1995, 51, 3675 NH2

OH N

N

O 11

H

H N

O N O

N H O

1.2 Guanidine Alkaloids

31

92 Isocrambescidin 800 Type: Triazaacenaphthylene alkaloids. C45H80N6O6 Oil, [α]D25 = –48° (c = 0.53, MeOH). Source: Sponge Crambe crambe (Mediterranean). Pharm: Ichthyotoxic. Ref: E. A. JaresErijman, et al, JOC, 1991, 56, 5712; 1993, 58, 4805│ R. G. S. Berlinch, et al, JNP, 1993, 56, 1007│ D. S. Coffey, et al, JACS, 1999, 121, 6944; 2000, 122, 4893; 4904 NH2 O

H

H N N O H

OH

N

O

13

15

O

N

O

NH2

93 Merobatzelladine A Type: Triazaacenaphthylene alkaloids. C23H42N31+ Pale brown oil (tetrafluoroacetate salt), [α]D25 = +37° (c = 0.68, MeOH) (tetrafluoroacetate salt). Source: Sponge Monanchora sp. (Amami-Oshima, Japan). Pharm: Antiplasmodial (Plasmodium falciparum); antitrypanosomal (Trypanosoma brucei brucei, sleeping sickness). Ref: S. Takishima, et al, Org. Lett., 2009, 11, 2655│ S. Takishima, et al, Org. Lett., 2010, 12, 896 H

H N

+

H 3

N H

N H

5

94 Merobatzelladine B Type: Triazaacenaphthylene alkaloids. C19H36N31+ Pale brown oil (tetrafluoroacetate salt), [α]D25 = +27° (c = 0.15, MeOH) (tetrafluoroacetate salt). Source: Sponge Monanchora sp. (Amami-Oshima, Japan). Pharm: Antiplasmodial (Plasmodium falciparum); antitrypanosomal (Trypanosoma brucei brucei, sleeping sickness). Ref: S. Takishima, et al, Org. Lett., 2009, 11, 2655│ S. Takishima, et al, Org. Lett., 2010, 12, 896 H

H N

+

H N H

N H

3

32

1 Amine Guanidine and Amide Alkaloids

95 Monanchocidin Monanchocidin A Type: Triazaacenaphthylene alkaloids. C47H82N6O8 Oil, [α]D = −12° (c = 0.4, EtOH). Source: Sponge Monanchora pulchra (psychrophilic, cold water, near Urup I., Southern Okhotsk Sea, Russia). Pharm: Cytotoxic (THP-1, IC50 = 5.1 μmol/L; HeLa, IC50 = 11.8 μmol/L; JB6 CI41, IC50 = 12.3 μmol/L); induces early apoptosis (THP-1, 3.0 μmol/L, 66%); cytotoxic (HL60, IC50 = 540 nmol/L, apoptosis-inducing activity). Ref: A. G. Guzii, et al, Org. Lett., 2010, 12, 4292│ S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev)

O

H N

O N H N

O

OH O

NH2

11

O O

N

OH

NH2

96 Monanchocidin B Type: Triazaacenaphthylene alkaloids. C45H78N6O8 Colorless oil, [α]D20 = −10.4° (c = 0.52, EtOH). Source: Sponge Monanchora pulchra (psychrophilic, cold water, near Urup I., Southern Okhotsk Sea, Russia). Pharm: Cytotoxic (HL60, IC50 = 200 nmol/L, apoptosis-inducing activity). Ref: T. N. Makarieva, et al, JNP, 2011, 74, 1952│ S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev)

O

O

H N

N H N

O

OH O

NH2

11

O

O

N

OH

NH2

1.2 Guanidine Alkaloids

33

97 Monanchocidin C Type: Triazaacenaphthylene alkaloids. C46H80N6O8 Colorless oil, [α]D20 = −23° (c = 0.13, EtOH). Source: Sponge Monanchora pulchra (psychrophilic, cold water, near Urup I., Southern Okhotsk Sea, Russia). Pharm: Cytotoxic (HL60, IC50 = 110 nmol/L, apoptosisinducing activity). Ref: T. N. Makarieva, et al, JNP, 2011, 74, 1952│ S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev)

O

O

H N

N H N

O

OH O

NH2

12

O O

N

OH

NH2

98 Monanchocidin D Type: Triazaacenaphthylene alkaloids. C45H78N6O8 Colorless oil, [α]D20 = −10° (c = 0.08, EtOH). Source: Sponge Monanchora pulchra (psychrophilic, cold water, near Urup I., Southern Okhotsk Sea, Russia). Pharm: Cytotoxic (HL60, IC50 = 830 nmol/L, apoptosisinducing activity). Ref: T. N. Makarieva, et al, JNP, 2011, 74, 1952│ S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev)

O

O

H N

N H N

O

OH NH2

O 11

O O

N

OH

NH2

99 Monanchocidin E Type: Triazaacenaphthylene alkaloids. C46H80N6O8 Colorless oil, [α]D20 = −10° (c = 0.09, EtOH). Source: Sponge Monanchora pulchra (psychrophilic, cold water, near Urup I., Southern Okhotsk Sea, Russia). Pharm: Cytotoxic (HL60, IC50 = 650 nmol/L,

34

1 Amine Guanidine and Amide Alkaloids

apoptosis-inducing activity). Ref: T. N. Makarieva, et al, JNP, 2011, 74, 1952│ S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev)

H N

O

O N H N

O

OH O

NH2

10

O O

N

OH

NH2

100 Neofolitispate 1 Type: Triazaacenaphthylene alkaloids. C40H67N3O6 Source: Sponge Neofolitispa dianchora (Andaman Is., India). Pharm: Antiviral (inhibits hepatitis B virus, 5 μg/mL). Ref: Y. Venkateswarlu, et al, Ind. J. Chem., Sect. B, 1999, 38, 254

O

H O N

N

O N

O O

16

O

101 Neofolitispate 2 Type: Triazaacenaphthylene alkaloids. C39H65N3O6 Oil, [α]D = −18° (c = 1, CHCl3). Source: Sponge Neofolitispa dianchora (Andaman Is., India). Pharm: Antiviral (inhibits hepatitis B virus, 5 μg/mL). Ref: Y. Venkateswarlu, et al, Ind. J. Chem., Sect. B, 1999, 38, 254

O

H N

N

O O

N

O 15

O

O

1.2 Guanidine Alkaloids

35

102 Neofolitispate 3 Type: Triazaacenaphthylene alkaloids. C38H63N3O6 Source: Sponge Neofolitispa dianchora (Andaman Is., India). Pharm: Antiviral (inhibits hepatitis B virus, 5 μg/mL). Ref: Y. Venkateswarlu, et al, Ind. J. Chem., Sect. B, 1999, 38, 254

O

H N

N

O O

N

O O

14

O

103 Norbatzelladine A Type: Triazaacenaphthylene alkaloids. C41H71N9O4 Oil, [α]D24 = +5° (c = 0.05, MeOH). Source: Sponge Monanchora arbuscula (Martinique, Caribbean Sea). Pharm: Cytotoxic (MDA-MB-231, GI50 = 3.8 μmol/L, TGI = 6.4 μmol/L, LC50 = 11.4 μmol/L; A549, GI50 = 2.1 μmol/L, TGI = 4.6 μmol/L, LC50 = 8.6 μmol/L; HT29, GI50 = 1.6 μmol/L, TGI = 3.2 μmol/L, LC50 = 5.7 μmol/L); antiplasmodial (in vitro Plasmodium falciparum FcB1, IC50 = 0.2 μmol/L, HeLa, TC50 = 4.7 μmol/L, SI (TC50/IC50) = 23.5). Ref: R. Laville, et al, JNP, 2009, 72, 1589 NH N

O

NH 8

O

N

H N

H 2N

3

O

O

N

N H

6

NH

104 Norbatzelladine L Type: Triazaacenaphthylene alkaloids. C38H66N6O2 Oil, [α]D24 = −2° (c = 0.2, MeOH). Source: Sponge Clathria calla (Guadeloupe I. (Fr.)). Pharm: Cytotoxic (MDA-MB-231, GI50 = 0.7 μmol/L, TGI = 1.9 μmol/L, LC50 = 4.8 μmol/L; A549, GI50 = 1.1 μmol/L, TGI = 2.1 μmol/L, LC50 = 4.2 μmol/L; HT29, GI50 = 1.2 μmol/L, TGI = 2.2 μmol/L, LC50 = 4.0 μmol/L); antiplasmodial (in vitro Plasmodium falciparum FcB1, IC50 = 0.4 μmol/L). Ref: R. Laville, et al, JNP, 2009, 72, 1589

36

1 Amine Guanidine and Amide Alkaloids

N

O

N H

N

N

O

5

N

N H

6

105 Ptilomycalin A Type: Triazaacenaphthylene alkaloids. C45H80N6O5 [α]D25 = –2.5° (c = 0.70, CHCl3). Source: Sponges Ptilocaulis spiculifer (Caribbean), Hemimycale sp. (Red Sea) and Batzella sp., starfish Celerina heffernani (New Caledonia). Pharm: Antiplasmodial (in vitro Plasmodium falciparum FcB1, IC50 = 0.1 μmol/L, HeLa, TC50 = 0.1 μmol/L, SI (TC50/IC50) = 1.4); anti-HIV-1 (cells CEM 4 infacted by HIV-1, CC50 = 0.11 μg/mL); cytotoxic (P388, IC50 = 0.1 μg/mL); antifungal (Candida albicans, MIC = 0.8 μg/mL); antiviral. Ref: Y. Kashman, et al, JACS, 1989, 111, 8925│ I. Ohtani, et al, JACS, 1992, 114, 8472│ E. Palagiano, et al, Tetrahedron, 1995, 51, 3675│ L. E. Overman, et al, JACS, 1995, 117, 2657│ A. D. Patil, et al, JOC, 1995, 60, 1182│ R. Laville, et al, JNP, 2009, 72, 1589 O

H N

NH2

36

O

N

NH2

43

H

O

5

N

N H

O

O

106 11-Deoxytetrodotoxin Type: Tetrodotoxins. C11H17N3O7 Needles (AcOH aq), mp 202 °C (dec), [α]D25 = +5.4°, (c = 0.3, AcOH aq). Source: Fishes Fugu spp., puffer fish Arothron nigropunctatus, newt Cynops ensicauda. Pharm: Paralytic poison; phycotoxin; Na ion blocker; LD50 (mus, ipr) = 0.71 mg/kg. Ref: T. Yasumoto, et al, Agric. Biol. Chem., 1986, 50, 793 OH HN

H

11

4 6 1

HN

N H HO

O OH O OH

OH

1.2 Guanidine Alkaloids

37

107 11-Nortetrodotoxin 11-Nortetrodotoxin-6S-ol Type: Tetrodotoxins. C10H15N3O7 Source: Puffer fish Arothron nigropunctatus. Pharm: Toxin. Ref: M. Yotsu, et al, Biosci., Biotechnol., Biochem., 1992, 56, 370 OH HN

H OH

4 6 1

N H

HN

HO

O OH O OH

108 Tetrodotoxin TTX Type: Tetrodotoxins. C11H17N3O8 Cryst., [α]D25 = −8.64° (c = 8.55, AcOH aq). Source: Dinoflagellate Alexandrium tarnavense, prosobranch (Japanese ivory shell) Babylonia japonica, puffer fishes Sphoeroides rubripes, Sphoeroides vermicularis and Sphoeroides phyreu (ovaries and liver, Japan), newts Taricha torosa (skin, California) and Cynops ensicauda, xanthid crab Atergatis floridus. Pharm: Sodium channels (I, II, III, μ1 and h1) blocker; highly potent toxin (non-protein, low molecular weight potent neurotoxin responsible for many hmn intoxications and fatalities each year); highly toxic (mammals, birds, reptiles, amphibians and fish); analgesic (could be used in the medical field as an analgesic to treat some cancer pains); LD50 (mus, orl) = 435 μg/kg; LD50 (mus, ivn) = 9 μg/kg; LD50 (mus, ipr) = 0.08 mg/kg. Ref: A. Yokoo, et al, Nippon Kagaku Kaishi, 1950, 71, 590│ J. W. J. Daly, Nat. Prod., 2004, 67, 1211 (rev)│ T. Noguchi, et al, Mar. Drugs, 2008, 6, 220 (rev, activity)│ CRC Press, DNP on DVD, 2012, version 20.2│ J. Lago, et al, Mar. Drugs 2015, 13, 6384 (rev). OH

OH H

HN HN

O N H HO

OH OH O OH

109 4-epi-Tetrodotoxin Type: Tetrodotoxins. C11H17N3O8 Amorph. Source: Puffer fish Arothron nigropunctatus, newt Cynops ensicauda, fish Fugu spp., cephalopod octopus Octopus maculosus. Pharm: Phycotoxin; sodium channel blocker; paralytic poison. Ref: T. Yasumoto, et al, Agric. Biol. Chem., 1986, 50, 793

38

1 Amine Guanidine and Amide Alkaloids

OH H HN

11

OH

4 6

OH

1

N H

HN

O OH

O

HO OH

110 6-epi-Tetrodotoxin Type: Tetrodotoxins. C11H17N3O8 Amorph., [α]D21 = −4.8° (c = 0.3, AcOH aq). Source: Fishes Fugu spp., puffer fish Arothron nigropunctatus, newt Cynops ensicauda. Pharm: Phycotoxin; LD50 (mus, ipr) = 0.6 mg/kg. Ref: T. Yasumoto, et al, Agric. Biol. Chem., 1986, 50, 793 OH H HN

11

4 6

OH

1

N H

HN

O OH

HO

OH

O

OH

111 5,6,11-Trideoxytetrodotoxin Type: Tetrodotoxins. C11H17N3O51+ [α]D23 = −17.4° (c = 0.5, HOAc). Source: Puffer fish Fugu poecilonotus (Japan). Pharm: Toxin. Ref: M. Yotsu-Yamashita, et al, Tet. Lett., 1995, 36, 9329 O HO HN

HH

OH

O

N N H OH

112 Gonyautoxin I GTX1 Type: Saxitoxins. C10H17N7O9S Source: Dinoflagellates Alexandrium tamarense, Gonyaulax spp. and Protogonyaulax spp., and occurs in other marine organisms. Pharm: Neurotoxin, causal agent, with Saxitoxin, of shellfish poisoning. Ref: B. L. Boyer, et al, J. Chem. Soc., Chem. Commun., 1978, 889│ Y. Shimizu, et al, J. Chem. Soc., Chem. Commun., 1981, 314│ C. F. Wichmann, et al, Tet. Lett., 1981,

1.2 Guanidine Alkaloids

39

22, 1941│ M. Alam, et al, Tet. Lett., 1982, 23, 321│ A. D. Cembella, et al, Harmful Algae, 2002, 1, 313│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) O O H H N

HO

NH2 NH

N NH OH

N

HN

11

O HO

S

OH

O

O

113 Gonyautoxin II GTX2 Type: Saxitoxins. C10H17N7O8S Source: Dinoflagellates Alexandrium tamarense, Gonyaulax spp. and Protogonyaulax spp., and occurs in other marine organisms. Pharm: Neurotoxin. Ref: B. L. Boyer, et al, J. Chem. Soc., Chem. Commun., 1978, 889│ Y. Shimizu, et al, J. Chem. Soc., Chem. Commun., 1981, 314│ C. F. Wichmann, et al, Tet. Lett., 1981, 22, 1941│ M. Alam, et al, Tet. Lett., 1982, 23, 321│ A. D. Cembella, et al, Harmful Algae, 2002, 1, 313│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) O O H H N

NH2 NH

HN NH OH

N

HN

OH

O HO

S

O

O

114 Gonyautoxin III GTX3 Type: Saxitoxins. C10H17N7O8S Source: Dinoflagellates Alexandrium tamarense, Gonyaulax spp. and Protogonyaulax spp., and occurs in other marine organisms. Pharm: Neurotoxin. Ref: B. L. Boyer, et al, J. Chem. Soc., Chem. Commun., 1978, 889│ Y. Shimizu, et al, J. Chem. Soc., Chem. Commun., 1981, 314│ C. F. Wichmann, et al, Tet. Lett., 1981, 22, 1941│ M. Alam, et al, Tet. Lett., 1982, 23, 321│ A. D. Cembella, et al, Harmful Algae, 2002, 1, 313│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)

40

1 Amine Guanidine and Amide Alkaloids

O O NH2

H H N

NH

HN NH OH

N

HN

O HO S O O

OH

115 Gonyautoxin IV GTX4 Type: Saxitoxins. C10H17N7O9S Source: Dinoflagellates Alexandrium tamarense, Gonyaulax spp. and Protogonyaulax spp., and occurs in other marine organisms. Pharm: Neurotoxin. Ref: B. L. Boyer, et al, J. Chem. Soc., Chem. Commun., 1978, 889│ Y. Shimizu, et al, J. Chem. Soc., Chem. Commun., 1981, 314│ C. F. Wichmann, et al, Tet. Lett., 1981, 22, 1941│ M. Alam, et al, Tet. Lett., 1982, 23, 321│ A. D. Cembella, et al, Harmful Algae, 2002, 1, 313│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) O O NH2 H HO

H N

NH

N NH OH

N

HN

OH

O HO

S

O

O

116 Gonyautoxin V GTX5; Toxin B1 Type: Saxitoxins. C10H17N7O7S Source: Dinoflagellates Alexandrium tamarense, Gonyaulax spp. and Protogonyaulax spp., and occurs in other marine organisms. Pharm: Neurotoxin. Ref: S. Hall, et al, Biochem. Biophys. Res. Commun., 1980, 97, 649│ Y. Shimizu, et al, Tetrahedron, 1984, 40, 539│ A. D. Cembella, et al, Harmful Algae, 2002, 1, 313│ M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)

1.2 Guanidine Alkaloids

O

O

O

N H

H

H

H N

N

41

S

OH

O NH

N H

N

HN

OH OH

117 Gonyautoxin VI GTX6; Toxin B2 Type: Saxitoxins. C10H18N7O8S Source: Dinoflagellate Protogonyaulax sp. Pharm: Neurotoxin; causal agent of shellfish poisoning. Ref: S. Hall, et al, Biochem. Biophys. Res. Commun., 1980, 97, 649│ Y. Shimizu, et al, Tetrahedron, 1984, 40, 539 O O O

N H

H

HO

H N

N

S

OH

O NH

HN

N H OH OH

N

118 Gonyautoxin VIII GTX8; Protogonyautoxin 2; Toxin C2; Toxin PX2 Type: Saxitoxins. C10H17N7O11S2 Large cryst. + H2O (H2O). Source: Dinoflagellates Alexandrium tamarense, Gonyaulax spp. and Protogonyaulax spp. Pharm: Neurotoxin. Ref: C. F. Wichmann, et al, JACS, 1981, 103, 6977│ Y. Shimizu, et al, Tetrahedron, 1984, 40, 539│ S. Hall, et al, Tet. Lett., 1984, 25, 3537│ A. D. Cembella, et al, Harmful Algae, 2002, 1, 313│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) O O OH S N O H H H N NH

O

HN HN

NH OH

N 11

OH

O HO S O

O

42

1 Amine Guanidine and Amide Alkaloids

119 Neosaxitoxin Type: Saxitoxins. C10H19N7O52+ Source: Dinoflagellates Alexandrium tamarense, Protogonyaulax sp., Pyrodinium sp. and Gonyaulax tamarensis, cyanobacterium Aphanizomenon flos-aquae, marine bacterium Vibrio sp., shellfish Saxidomus giganteus. Pharm: Neurotoxin; neuromuscular blocker; neurotoxin (potent); LD50 (mus, ipr) 5 mg/kg. Ref: B. L. Boyer, et al, J. Chem. Soc., Chem. Commun., 1978, 889│ Y. Shimizu, et al, J. Chem. Soc., Chem. Commun., 1981, 314│ C. F. Wichmann, et al, Tet. Lett., 1981, 22, 1941│ M. Alam, et al, Tet. Lett., 1982, 23, 321│ A. D. Cembella, et al, Harmful Algae, 2002, 1, 313│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) O O NH2

H H N

HO

N

N H

N

+

+

H

NH OH

N

H

H

OH

120 Saxitoxin Type: Saxitoxins. C10H17N7O4 Non-cryst., [α]D = +130°. Source: Dinoflagellates Gonyaulax catenella and Protogonyaulax tamarensis, butter clam Saxidomus giganteus (Alaska), mussel (blue mussel) Mytilus californianus (toxic), and occurs in other marine organisms. Pharm: Sodium channels (I, II, III and h1) blocker; causal agent of paralytic shellfish poisoning, extremely toxic (among most toxic substances known), LD50 (rat, orl) = 0.192 mg/kg; LD50 (mus, ipr) = 0.005 mg/kg; LD50 (mus, ivn) = 0.008 mg/kg. Ref: E. J. Schantz, et al, JACS, 1975, 97, 1238│ J. Bordner, et al, JACS, 1975, 97, 6008│ Y. Shimizu, et al, JACS, 1978, 100, 6791│ P. A. Jacobi, et al, JACS, 1984, 106, 5594│ S. Hall, et al, Tet. Lett., 1984, 25, 3537│ M. Kodama, et al, Agric. Biol. Chem., 1988, 52, 1075│ A. D. Cembella, et al, Harmful Algae, 2002, 1, 313│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)│ CRC Press, DNP on DVD, 2012, version 20.2 O O H HN H

N H

H N

NH2 H N

H N

+

N

+

H OH

OH

1.2 Guanidine Alkaloids

43

121 Toxin C1 Toxin PX1 Type: Saxitoxins. C11H17N7O11S2 Prisms + H2O (MeOH aq). Source: Dinoflagellate Alexandrium tamarense. Pharm: Neurotoxin. Ref: A. D. Cembella, et al, Harmful Algae, 2002, 1, 313│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)

O S

HO

H N

O

O H

O

H N

HN

NH N H

N

HN

OH O

H O

OH

S O

OH

122 Toxin C3 Protogonyautoxin 3 Type: Saxitoxins. C10H17N7O12S2 Source: Dinoflagellate Protogonyaulax catenella. Pharm: Toxin. Ref: T. Noguchi, et al, Bull. Jpn. Soc. Sci. Fish., 1983, 49, 1931│ S. Hall, et al, Tet. Lett., 1984, 25, 3537 O O H

HO N

O N H

S O O H

H N N

H N

+

N H

N

H O O

+

H

OH H OH

S O O

123 Toxin C4 Type: Saxitoxins. C10H17N7O12S2 Source: Dinoflagellate Protogonyaulax catenella. Pharm: Toxin. Ref: T. Noguchi, et al, Bull. Jpn. Soc. Sci. Fish., 1983, 49, 1931│ S. Hall, et al, Tet. Lett., 1984, 25, 3537

44

1 Amine Guanidine and Amide Alkaloids

O

O

O H

HO N

N H H N

S

H N

H N

+

+

H

N H

N

H

O

O

OH O H OH O S O O

1.3 Amide Alkaloids 124 2-[ (2-Acetamidopropanoyl)amino]benzamide Antibiotic NI 15501A Type: Simple amide alkaloids. C12H15N3O3 Solid, mp 203–205 °C, [α]D30 = −62.8° (c = 0.147, MeOH). Source: Marine-derived fungus Penicillium sp. N115501 (Japan). Pharm: Antimicrobial. Ref: H. Onuki, et al, J. Antibiot., 1998, 51,442 O N H O

H 2N

H N O

125 N- (1-Acetoxymethyl-2-methoxyethyl)-7-methoxy-4-eicosenamide Type: Simple amide alkaloids. C27H51NO5 Colorless needles, mp 39–40.5 °C, [α]D20 = −6.1° (c = 0.58, CHCl3). Source: An unidentified cyanobacterium (King George River, Northwestern Australia). Pharm: Anti-HIV (weak). Ref: C. Le, et al, Chin. J. Mar. Drugs. 1999, 18 (2), 12│ F. Wan, et al, JNP, 1999, 62, 1696 O

H N O

12

OMe

O OMe

126 Axidjiferoside A Type: Simple amide alkaloids. C49H95NO5 Source: Sponge Axinyssa djiferi from an unidentified mangrove (tree roots, Djifer, Senegal). Pharm: Antiplasmodial (using mixture of Axidjiferoside A, B and C, CRPF). Ref: F. Farokhi, et al, Mar. Drugs, 2013, 11, 1304

1.3 Amide Alkaloids

45

HO 20

O

OH

OH

NH

O 9

HO

OH

OH OH

127 Axidjiferoside B Type: Simple amide alkaloids. C48H93NO5 Source: Sponge Axinyssa djiferi from an unidentified mangrove (tree roots, Djifer, Senegal). Pharm: Antiplasmodial (using mixture of Axidjiferoside A, B and C, CRPF). Ref: F. Farokhi, et al, Mar. Drugs, 2013, 11, 1304 HO 19

O

OH

OH

NH

O 9

HO

OH

OH OH

128 Axidjiferoside C Type: Simple amide alkaloids. C50H97NO5 Source: Sponge Axinyssa djiferi from an unidentified mangrove (tree roots, Djifer, Senegal). Pharm: Antiplasmodial (using mixture of Axidjiferoside A, B and C, CRPF). Ref: F. Farokhi, et al, Mar. Drugs, 2013, 11, 1304 HO 21

O

OH

NH

OH

O 9

HO

OH

OH

OH

129 3-Bromo-5-hydroxy-4-methoxybenzamide Type: Simple amide alkaloids. C8H8BrNO3 Colourless powder. Source: Red alga Rhodomela confervoides (Dalian, Liaoning Province, China). Pharm: Antioxidant (DPPH scavenger, IC50 = (23.60 ± 0.10)μmol/L, control BHT, IC50 = (82.10 ± 0.20) μmol/L); antioxidant (ABTS+ radical cation scavenger, TEAC = (2.11 ± 0.04) mmol/ L, control Ascorbic acid, TEAC = (1.02 ± 0.01)mmol/L). Ref: K. Li, et al, Food Chem., 2012, 135, 868

46

1 Amine Guanidine and Amide Alkaloids

O Br

NH2

O OH

130 2- (3-Bromo-5-hydroxy-4-methoxyphenyl)acetamide Type: Simple amide alkaloids. C9H10BrNO3 Colourless powder. Source: Red alga Rhodomela confervoides (Dalian, Liaoning Province, China). Pharm: Antioxidant (DPPH scavenger, IC50 = (20.81 ± 0.08)μmol/L, control BHT, IC50 = (82.10 ± 0.20) μmol/L); antioxidant (ABTS+ radical cation scavenger, TEAC = (2.36 ± 0.08)mmol/L, control Ascorbic acid, TEAC = (1.02 ± 0.01)mmol/L). Ref: K. Li, et al, Food Chem., 2012, 135, 868 NH2

Br O

O OH

131 Complanine Type: Simple amide alkaloids. C18H35N2O21+ [α]D25 = −10° (c = 1, H2O). Source: Marine fireworm Eurythoe complanata. Pharm: Inflammatory (enhancer of phosphorylation with PKC in presence of Ca2+ and TPA with dose-dependent manner). Ref: K. Nakamura, et al, Org. Biomol. Chem., 2008, 6, 2058│ K. Nakamura, et al, Beilstein JOC, 2009, 5, 12│ K. Nakamura, et al, JNP, 2010, 73, 303 O R

OH

N

+

N H

132 2,6-Dibromo-4-acetamido-4-hydroxycyclohexadienone 3,5-Dibromoverongiaquinol Type: Simple amide alkaloids. C8H7Br2NO3 Needles (Et2O/Me2CO), mp 195–196 °C. Source: Sponges Verongia fistularis, Verongia cauliformis and Aplysina fistularis. Pharm: Antibiotic. Ref: G. M. Sharma, et al, Tet. Lett., 1967, 8, 4147│ G. M. Sharma, et al, JOC, 1970, 35, 2823│ A. A. Tymiak, et al, JACS, 1981, 103, 6763

1.3 Amide Alkaloids

47

O Br

Br

HO O

NH2

133 4- (2,3-Dibromo-4,5-dihydroxybenzylamino)-4-oxobutanoic acid Type: Simple amide alkaloids. C11H11Br2NO5 Yellowish oil. Source: Red alga Rhodomela confervoides (Dalian, Liaoning Province, China). Pharm: Antioxidant (DPPH scavenger, IC50 = (5.43 ± 0.02)μmol/L, control BHT, IC50 = (82.10 ± 0.20)μmol/L); antioxidant (ABTS+ radical cation scavenger, TEAC = (2.31 ± 0.11)mmol/L, control Ascorbic acid, TEAC = (1.02 ± 0.01)mmol/L). Ref: K. Li, et al, Food Chem., 2012, 135, 868 O

Br Br

N H OH

HO O

OH

134 4,5-Dibromo-N2-methoxymethyl-1H-pyrrole-2-carboxamide Type: Simple amide alkaloids. C7H8Br2N2O2 Source: Sponge Homaxinella sp. (deep water, Japan). Pharm: Cytotoxic (P388, ED50 = 21.5 μg/mL). Ref: I. Mancini, et al, Tet. Lett., 1997, 38, 6271│ A. Umeyama, et al, JNP, 1998, 61, 1433 Br H N Br

N H O

O

135 Flavochristamide A Type: Simple amide alkaloids. C34H67NO6S White solid, mp 216–218 °C, [α]D20 = −17° (nat., c = 0.27, MeOH), [α]D26 = −18.7° (syn., c = 0.17, MeOH). Source: Marinederived bacterium Flavobacterium sp. from bivalve Cristaria plicata. Pharm: DNA polymerase α inhibitor (calf thymus). Ref: J. Kobayashi, et al, Tetrahedron, 1995, 51, 10487│ H. Takikawa, et al, JCS Perkin I, 1999, 2467│ T. Shioiri, et al, Tetrahedron, 2000, 56, 9129

48

1 Amine Guanidine and Amide Alkaloids

OH

O

OH H N

4 5

O O

S OH

136 Flavochristamide B Sulfobacin A Type: Simple amide alkaloids. C34H69NO6S White solid, mp 220–222 °C, [α]D18 = −31.6° (syn., c = 0.14, MeOH), [α]D24 = −35° (nat., c = 0.14, MeOH). Source: Marine-derived bacterium Flavobacterium sp. from bivalve mollusc Cristaria plicata, marine-derived bacterium Flavobacterium sp. NR2993 (culture broth, soil sample, Iriomote I., Okinawa, Japan). Pharm: Inhibits competitively banding of von Willebrand facter to GPIb/IX receptors (IC50s = 0.47 μmol/L); DNA polymerase α inhibitor (calf thymus). Ref: T. Kamiyama, et al, J. Antibiot., 1995, 48, 924; 929│ J. Kobayashi, et al, Tetrahedron, 1995, 51, 10487│ H. Takikawa, et al, JCS Perkin I, 1999, 2467│ T. Shioiri, et al, Tetrahedron, 2000, 56, 9129 OH

O OH H N

4 5

O S O OH

137 N-Formyl-2- (4-hydroxyphenyl)acetamide Type: Simple amide alkaloids. C9H9NO3 Source: An unidentified marine fungus from brown alga Ishige okamurae (Korea). Pharm: Antioxidant (DPPH radical scavenger, more active than control Ascorbic acid). Ref: X. F. Li, et al, J. Microbiol. Biotechnol., 2006, 16, 637 H N

HO

O

H O

138 Grenadamide B Type: Simple amide alkaloids. C21H36ClNO2 Oil, [α]D23 = −8.7° (c = 0.4, CH2Cl2). Source: Cyanobacterium Lyngbya majuscula. (True Blue Bay, Grenada). Pharm: Insecticidal (beet armyworm Spodoptera exigua, marginal). Ref: J. I. Jiménez, et al, JNP, 2009, 72, 1573

1.3 Amide Alkaloids

49

Cl O

16

N H O

139 Grenadamide C Type: Simple amide alkaloids. C21H35Cl2NO2 Light yellow oil, [α]D23 = −17° (c = 0.4, CH2Cl2). Source: Cyanobacterium Lyngbya majuscula. (True Blue Bay, Grenada). Pharm: Insecticidal (beet armyworm Spodoptera exigua, marginal). Ref: J. I. Jiménez, et al, JNP, 2009, 72, 1573 Cl O

16

N H

Cl O

140 Gymnastatin Q Type: Simple amide alkaloids. C24H35Cl2NO5 Powder, mp 105–108 °C, [α]D23 = −34.3° (c = 0.26, CHCl3). Source: Marine-derived fungus Gymnascella dankaliensis from sponge Halichondria japonica (off Osaka, Japan). Pharm: Cytotoxic (P388, BSY1 and MKN7, growth inhibition). Ref: T. Amagata, et al, JNP, 2008, 71, 340 O Cl

Cl 6

OH

O

5

O

1

HO

N H

141 N- (1′R-Hydroxymethyl-2-methoxyethyl)-7S-methoxy-4E-eicosenamide Type: Simple amide alkaloids. C25H49NO4 Colorless plates, mp 32–34 °C, [α]D20 = −3.0° (c = 0.33, CHCl3). Source: An unidentified cyanobacterium (King George River, Northwestern Australia). Pharm: Anti-HIV (weak). Ref: C. Le, et al, Chin. J. Mar. Drugs. 1999, 18 (2), 12│ F. Wan, et al, JNP, 1999, 62, 1696 H N OH

12

OMe

O OMe

50

1 Amine Guanidine and Amide Alkaloids

142 3- (3-Indolyl)acrylamide Type: Simple amide alkaloids. C11H10N2O Amber cryst. (Me2CO), mp 212.8–214.2 °C. Source: Red alga Chondria atropurpurea. Pharm: Anthelmintic (EC80 = 2.34 mmol/L). Ref: D. Davyt, et al,, JNP, 1998, 61, 1560 O NH2

N H

143 Janthielamide A Type: Simple amide alkaloids. C18H28ClNO Source: Cyanobacterium “tropical marine Symploca sp.” (Curacao and Papua New Guinea). Pharm: Sodium channel blocker (murine Neuro-2a cells, moderate); antagonist of veratridine-induced sodium infiux (murine cerebrocortical neurons). Ref: J. K. Nunnery, et al, JOC, 2012, 77, 4198 Cl O N H

144 JBIR 66 Type: Simple amide alkaloids. C19H32N2O4 Source: Marine-derived bacterium Saccharopolyspora sp. from an unidentified ascidian (Tateyama City, Chiba, Japan). Pharm: Cytotoxic (hmn lymphoblastoid namalva cells, weak). Ref: M. Takagi, et al, Biosci., Biotechnol., Biochem., 2010, 74, 2355 O NH OH H N

HO O

145 Kimbeamide A Type: Simple amide alkaloids. C17H23Cl2NO Source: Cyanobacteria “tropical marine Symploca sp.” (consortium) and Moorea producens (Kime Bay, New Britain I.,

1.3 Amide Alkaloids

51

Papua New Guinea). Pharm: Sodium channel blocker (murine Neuro-2a cells, moderate). Ref: J. K. Nunnery, et al, JOC, 2012, 77, 4198 Cl

Cl

O N H

4E

2'z

146 Korormicin A Type: Simple amide alkaloids. C25H39NO5 (5S, 3’R, 9’S, 10’R): [α]D30 = −24.5° (c = 0.828, EtOH), (5S, 3’S, 9’S, 10’R): [α]D30 = −12.1° (c = 0.844, EtOH), (5S, 3’S, 9’R, 10’S): [α]D29 = −16.9° (c = 1.27, EtOH), (5S, 3’R, 9’R, 10’S): [α]D30 = −29.6° (c = 1.04, EtOH). Source: Marine bacterium Pseudoalteromonas sp. F-420 from green alga Halimeda sp. (surface, Palau). Pharm: Antibacterial (fish in aquaculture, against diseases caused by gramnegative bacteria); inhibits growth of marine bacteria but doesn’t affect terrestrial species. Ref: K. Yoshikawa, et al, J. Antibiot., 1997, 50, 949│ H. Uehara, et al, Tet. Lett., 1999, 40, 8641│ Y. Kobayashi, et al, Tet. Lett., 2000, 41, 1465

O O

O

N H

OH

O

147 Lorneamide A Type: Simple amide alkaloids. C17H23NO2 Colorless glass, [α]D25 = −7.2° (c = 0.20, MeOH). Source: An unidentified marine-derived actinomycete (beach of Southern Australia). Pharm: Antibacterial (Bacillus subtilis, LD99 = 50.0 μg/mL). Ref: R. J. Capon, et al, JNP, 2000, 63, 1682 O NH2 OH

52

1 Amine Guanidine and Amide Alkaloids

148 Malonganenone K Type: Simple amide alkaloids. C21H35NO2 Colorless oil. Source: Gorgonian Euplexaura robusta (Weizhou I., Guangxi, China). Pharm: Cytotoxic (HeLa, IC50 = (57.82 ± 2.37)μmol/L, control Adriamycin, IC50 = (0.38 ± 0.05)μmol/L; K562, IC50 > 100 μmol/L, Adriamycin, IC50 = (0.23 ± 0.02)μmol/L). Ref: J. -R. Zhang, et al, Chem. Biodiversity, 2012, 9, 2218 O

O H

N H

3

149 Methyl 4- (2,3-dibromo-4,5-dihydroxybenzylamino)-4-oxobutanoate Type: Simple amide alkaloids. C12H13Br2NO5 Yellowish oil. Source: Red alga Rhodomela confervoides (Dalian, Liaoning Province, China). Pharm: Antioxidant (DPPH scavenger, IC50 = (5.70 ± 0.03)μmol/L, control BHT, IC50 = (82.10 ± 0.20)μmol/L); antioxidant (ABTS+ radical cation scavenger, TEAC = (2.14 ± 0.08)mmol/L, control Ascorbic acid, TEAC = (1.02 ± 0.01)mmol/L). Ref: K. Li, et al, Food Chem., 2012, 135, 868 O

Br Br

N H

O

HO O

OH

150 3-Methyl-N- (2’-phenylethyl)-butyramide Type: Simple amide alkaloids. C13H19NO Source: Marine bacterium Halobacillus salinus. Pharm: Antibacterial (quorum sensing, IC50 = 9 μg/mL, MMOA: inhibits homoserine lactone receptor binding). Ref: M. E. Teasdale, et al, Appl. Environ. Microbiol. 2009, 75, 567 H N O

151 Motualevic acid A Type: Simple amide alkaloids. C16H25Br2NO3 Amorph. solid. Source: Lithistid sponge Siliquariaspongia sp. (Motualevu Reef, Fiji). Pharm: Antibacterial (Staphylococcus aureus, MIC50 = 10.9 μg/mL; MRSA, MIC50 = 21 μg/mL); antibacterial (agar disk diffusion assay, Staphylococcus aureus, 10 μg/mL, IZD = 8–11 mm; MRSA, 10 μg/mL, IZD = 8–11 mm). Ref: J. L. Keffer, et al, Org. Lett., 2009, 11, 1087│ P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

1.3 Amide Alkaloids

53

Br H N Br

7

O

O

OH

152 Motualevic acid B Type: Simple amide alkaloids. C16H26Br2NO3 Amorph. solid. Source: Lithistid sponge Siliquariaspongia sp. (Motualevu Reef, Fiji). Pharm: Antibacterial (agar disk diffusion assay, Staphylococcus aureus, 10 μg/mL, IZD = 8–11 mm; MRSA, 25 μg/mL, inactive). Ref: J. L. Keffer, et al, Org. Lett., 2009, 11, 1087│ P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev) H N Br O Br

7

O

OH

153 Motualevic acid C Type: Simple amide alkaloids. C16H26Br2N2O2 Amorph. solid. Source: Lithistid sponge Siliquariaspongia sp. (Motualevu Reef, Fiji). Pharm: Antibacterial (microbroth dilution assay, Staphylococcus aureus, MIC50 = (173 ± 33)μg/mL; MRSA, MIC50 = (400 ± 110)μg/mL). Ref: J. L. Keffer, et al, Org. Lett., 2009, 11, 1087│ P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev) Br H N Br

7

O O

NH2

154 Motualevic acid E Type: Simple amide alkaloids. C14H22Br2O2 Source: Lithistid sponge Siliquariaspongia sp. (Motualevu reef, Fiji). Pharm: Antibacterial (agar disk diffusion assay, Staphylococcus aureus, 50 μg/mL, IZD = 8–11 mm; MRSA, 50 μg/mL, inactive). Ref: J. L. Keffer, et al, Org. Lett., 2009, 11, 1087│ P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev) Br OH Br O

54

1 Amine Guanidine and Amide Alkaloids

155 Neocomplanine A Type: Simple amide alkaloids. C16H35N2O2 Source: Marine fireworm Eurythoe complanata. Pharm: Inflammatory; PKC activator (> 0.5 mmol in presence of Ca2+, weak activity; in presence of 1.2 μmol/L TPA, enhanced activity with dose-dependently manner). Ref: K. Nakamura, et al, JNP, 2010, 73, 303 O N

+

N H OH

156 Neocomplanine B Type: Simple amide alkaloids. C14H31N2O2 Source: Marine fireworm Eurythoe complanata. Pharm: Inflammatory; PKC activator (> 0.5 mmol in presence of Ca2+, weak activity; in presence of 1.2 μmol/L TPA, enhanced activity with dose-dependently manner). Ref: K. Nakamura, et al, JNP, 2010, 73, 303 O N+ N H OH

157 Pitiamide A Type: Simple amide alkaloids. C22H36ClNO2 [α]D = −10.3° (c = 3, CHCl3). Source: Cyanobacterium Lyngbya majuscula and Microcoleus sp. (mixture) growing on hard coral Porites cylindrica (Guam). Pharm: LD50 = 0.05 μg/mL. Ref: D. G. Nagle, et al, Tet. Lett., 1997, 38, 6969│ S. Ribe, et al, JACS, 2000, 122, 4608 H N Cl O

O

158 PM050489 Type: Simple amide alkaloids. C31H44ClN3O7 Source: Sponge Lithoplocamia lithistoides (Madagascar). Pharm: Cytotoxic (sulforhodamine B method, HT29, GI50 = 0.46 nmol/L, A549, GI50 = 0.38 nmol/L, MDA-MB-231, GI50 = 0.45 nmol/L); antimitotic (modified cell-based immunoassay using specific mitotic marker MPM-2, IC50 = 26.4 nmol/L (0.016 μg/mL)). Ref: M. J. Martin, et al, JACS, 2013, 135, 10164

1.3 Amide Alkaloids

55

O O O

O

NH2

O

N H

HN

O O

Cl

159 PM060184 Type: Simple amide alkaloids. C31H45N3O7 Source: Sponge Lithoplocamia lithistoides (Madagascar). Pharm: Cytotoxic (sulforhodamine B method, HT29, GI50 = 0.42 nmol/L, A549, GI50 = 0.59 nmol/L, MDA-MB-231, GI50 = 0.61 nmol/L, a promising drug for cancer treatment); antimitotic (modified cell-based immunoassay using specific mitotic marker MPM-2); antineoplastic (phase I clinical trials in 2011). Ref: M. J. Martin, et al, JACS, 2013, 135, 10164 O O O

O

NH2

O

N H

HN

O O

H

160 Serinolamide A Type: Simple amide alkaloids. C23H45NO3 Source: Cyanobacteria Lyngbya majuscula (New Ireland, Papua New Guinea) and Oscillatoria sp. (Isla Canales de Afuera, Coiba National Park, Panama). Pharm: Agonist of CB1 cannabinoid receptor (selective, IC50 = (2.3 ± 0.1)μmol/L, Ki = 1.3 μmol/L, moderate). Ref: M. Gutiérrez, et al, JNP, 2011, 74, 2313 OH O O N

161 Serinolamide B Type: Simple amide alkaloids. C22H43NO3 Source: Cyanobacterium Lyngbya sp. (Piti Bomb Holes, Guam). Pharm: Cannabinomimetics (decreasing forskolin-induced

56

1 Amine Guanidine and Amide Alkaloids

cAMP accumulation). Ref: J. H. Cardellina II, et al, Phytochemistry, 1978, 17, 2091│ R. Montaser, et al, ChemBioChem, 2012, 13, 2676

OH O O N H

162 Sinulasulfone Type: Simple amide alkaloids. C23H47NO3S Source: Soft coral Sinularia sp. (Manado, North Sulawesi, Indonesia). Pharm: NO release inhibitor (LPS-stimulated macrophages). Ref: M. Y. Putra, et al, Tet. Lett., 2012, 53, 3937 O

O

S N H

O

163 Sinulasulfoxide Type: Simple amide alkaloids. C23H47NO2S Source: Soft coral Sinularia sp. (Manado, North Sulawesi, Indonesia). Pharm: NO release inhibitor (LPS-stimulated macrophages). Ref: M. Y. Putra, et al, Tet. Lett., 2012, 53, 3937 O

O

S N H

164 Somocystinamide A Type: Simple amide alkaloids. C42H70N4O4S2 Amorph. solid, [α]D22 = +13.5° (c = 0.75, CHCl3). Source: Cyanobacteria Lyngbya majuscula and Schizothrix sp. (assemblage), cyanobacterium Lyngbya majuscula. Pharm: Cytotoxic (neuro-2a); cytotoxic (XTT assay, Jurkat and CEM, A549, Molt4, M21 and U266). Ref: L. M. Nogle, et al, Org. Lett., 2002, 4, 1095│ W. Wrasidlo,et al, Proc. Natl. Acad. Sci. USA 2008, 105, 2313

1.3 Amide Alkaloids

57

O NH N O

S

O

S

N NH O

165 Synechobactin A Type: Simple amide alkaloids. C26H48N4O9 Source: Cyanobacterium Synechococcus sp. PCC 7002. Pharm: Siderophore. Ref: Y. Ito, et al, Limnol. Oceanogr., 2005, 50, 1918 O H

N

N

OH O OH O

COOH 1

O

N

N

H

OH

166 Terremide A Type: Simple amide alkaloids. C21H17N3O5 White amorph. powder. Source: Marine-derived fungus Aspergillus terreus PT06-2 (Grown in High Salt Medium 10% salinity). Pharm: Antibacterial (Staphylococcus aureus, MIC = 63.9 μmol/L; control Ciprofloxacin lactate, MIC = 1.0 μmol/L; Enterobacter aerogenes and Pseudomonas aeruginosa, MIC > 100 μmol/L); antifungal (Candida albicans, MIC > 100 μmol/L, control Ketoconazole, MIC = 5 μmol/L). Ref: Y. Wang, et al, Mar. Drugs, 2011, 9, 1368 HO O N H NH O

O

O N

58

1 Amine Guanidine and Amide Alkaloids

167 Terremide B Type: Simple amide alkaloids. C21H15N3O4 Colorless crystal. Source: Marine-derived fungus Aspergillus terreus PT06-2 (Grown in High Salt Medium 10% salinity). Pharm: Antibacterial (Enterobacter aerogenes, MIC = 33.5 μmol/L, control Ciprofloxacin lactate, MIC = 1.0 μmol/L; Staphylococcus aureus and Pseudomonas aeruginosa, MIC > 100 μmol/L); antifungal (Candida albicans, MIC > 100 μmol/L, control Ketoconazole, MIC = 5 μmol/L). Ref: Y. Wang, et al, Mar. Drugs, 2011, 9, 1368 O O

O N OH N

N

168 Trichodermamide A Penicillazine Type: Simple amide alkaloids. C20H20N2O9 Needles (Me2CO), mp 258–260 °C, mp 224–226 °C, [α]D15 = +128° (c = 0.15, MeOH), [α]D25 = −11.9° (c = 2.2, CHCl3). Source: Marine-derived fungus Penicillium sp. 386 (collected from sand in a marine habitat, South China Sea). Pharm: Cytotoxic. Ref: Y. Lin, et al, Tetrahedron, 2000, 56, 9607│ M. Saleem, et al, NPR, 2007, 24, 1142 (rev) O

OH

O

OH

OH

H

O

N

O O

N H O

169 Trichodermamide B Type: Simple amide alkaloids. C20H19ClN2O8 Oil, [α]D15 = +110.7° (c = 0.15, MeOH). Source: Marine-derived fungus Trichoderma virens (cultures). Pharm: Cytotoxic (HCT116, IC50 = 0.32 μg/mL). Ref: M. Saleem, et al, NPR, 2007, 24, 1142 (rev)

1.3 Amide Alkaloids

59

O

Cl

O

O

OH O

N H N

O

O H OH

170 Turbinamide Type: Simple amide alkaloids. C32H65NO12S Source: Ascidian Sidnyum turbinatum (Mediterranean). Pharm: Cytotoxic (selective). Ref: A. Aiello, et al, Org. Lett., 2001, 3, 2941 O O

OH

OH

O

S

O

H

O

H 2N OH

OH

OH

OH

OH

171 Circumdatin C Type: Benzodiazepine alkaloids. C17H13N3O3 Solid, [α]D22 = −75° (c = 0.16, MeOH). Source: Marine-derived fungus Exophiala sp. MFC353-1 from sponge Halichondria panicea (surface, Korea), terrestrial fungus (Aspergillus ochraceus). Pharm: UV-A protecting (exceeded control, commercially applied sunscreen agent oxybenzone). Ref: L. Rahbæk, et al, JOC, 1999, 64, 1689│ D. H. Zhang, et al, J. Antibiot., 2008, 61, 40 O HO

5

H N N O

N

15

172 Circumdatin F Type: Benzodiazepine alkaloids. C17H13N3O2 Source: Deep-sea fungus Aspergillus westerdijkiae SCSIO 05233. Pharm: Antifoulant (EC50 = 8.81 μg/mL). Ref: M. Fredimoses, et al, Nat. Prod. Res. 2015, 29, 158

60

1 Amine Guanidine and Amide Alkaloids

O N N

O

N H

173 Circumdatin G Type: Benzodiazepine alkaloids. C17H13N3O3 Powder, [α]D = −21.7° (c = 0.2, MeOH). Source: Marine-derived fungus Exophiala sp. MFC353-1 from sponge Halichondria panicea (surface, Korea), marine-derived fungus Aspergillus ochraceus, deep-sea fungus Aspergillus westerdijkiae SCSIO 05233. Pharm: UV-A protecting (exceeded control, commercially applied sunscreen agent oxybenzone); cytotoxic (K562, IC50 = 25.8 μmol/L; HL60 cells, IC50 = 44.9 μmol/L, antiproliferation, weak). Ref: J. R. Dai, et al, JNP, 2001, 64, 125│ D. H. Zhang, et al, J. Antibiot., 2008, 61, 40│ M. Fredimoses, et al, Nat. Prod. Res. 2015, 29, 158 O 5

H N N N

O

15

OH

174 Circumdatin I Type: Benzodiazepine alkaloids. C17H13N3O4 Amorph. solid, [α]D20 = −236° (c = 0.2, MeOH). Source: Marine-derived fungus Exophiala sp. from sponge Halichondria panicea (surface, Korea). Pharm: Ultraviolet A-protecting (IC50 = 98 μmol/L, commercially applied sunscreen agent oxybenzone). Ref: Y. Zhang, et al, Chem. Biodivers. 2008, 5, 93│ D. Zhang, et al, J. Antibiot., 2008, 61, 40 O HO

5

H N N O

N 15

OH

1.3 Amide Alkaloids

61

175 2-Hydroxycircumdatin C 6-Hydroxycircumdatin C Type: Benzodiazepine alkaloids. C17H15N3O4 Amorph. powder, [α]D22 = −68.7° (c = 0.11, MeOH). Source: Marine-derived fungus Aspergillus ochraceus from brown alga Sargassum kjellmanianum (China). Pharm: Antioxidant (DPPH radical scavenger, more potent than control BHT). Ref: C. M. Cui, et al, Helv. Chim. Acta, 2009, 92, 1366 O HO

H N

HO N N

O

176 Limazepine G Type: Benzodiazepine alkaloids. C16H16N2O3 Source: Marine-derived streptomycete Streptomyces seoulensis from shrimp Penaeus orientalis (gut, Qingdao, China). Pharm: Neuraminidase inhibitor. Ref: R. H. Jiao, et al, J. Appl. Microbiol., 2013, 114, 1046 O N

N H

O

OH

177 Cathestatin A Antibiotic PF 1126A Type: Cinnamic acid amides. C17H23N3O5 Amorph. solid. Source: Marine-derived fungus Microascus longirostris SF-73 from an unidentified sponge (New Zealand). Pharm: Proteases inhibitors (Cysteine proteases: Cathepsin L, IC50 = 0.007 μg/mL; Cathepsin B, IC50 = 0.260 μg/mL; Papain, IC50 = 0.360 μg/mL; Ficin, IC50 = 0.230 μg/mL; Bromelain, IC50 = 1.010 μg/mL; Serine proteases: Trypsin, IC50 > 100 μg/mL; Chymostatin, IC50 > 100 μg/mL; Metal protease: Thermolysin, IC50 > 100 μg/mL; Aspartic protease: Cathepsin D, IC50 > 100 μg/mL); Cysteine proteases inhibitor (Papain, IC50 = 11.2 nmol/L, Cathepsin B, IC50 = 177.6 nmol/L, Cathepsin L, IC50 = 1.4 nmol/L). Ref: J. -T. Woo, et al, Biosci., Biotechnol., Biochem., 1995, 59, 350│ C. -M. Yu, et al, J. Antibiot., 1996, 49, 395

62

1 Amine Guanidine and Amide Alkaloids

O

O

O H N

HO

NH2

N H

O

178 Cathestatin B Antibiotic PF 1126B Type: Cinnamic acid amides. C17H23N3O6 Amorph. solid. Source: Marine-derived fungus Microascus longirostris SF-73 from an unidentified sponge (New Zealand). Pharm: Proteases inhibitors (Cysteine proteases: Cathepsin L, IC50 = 0.009 μg/mL; Cathepsin B, IC50 = 0.280 μg/mL; Papain, IC50 = 0.230 μg/mL; Ficin, IC50 = 0.280 μg/mL; Bromelain, IC50 = 0.580 μg/mL; Serine proteases: Trypsin, IC50 > 100 μg/mL; Chymostatin, IC50 > 100 μg/mL; Metal protease: Thermolysin, IC50 > 100 μg/mL; Aspartic protease: Cathepsin D, IC50 > 100 μg/mL); cysteine proteases inhibitor (papain, IC50 = 4.6 nmol/L, Cathepin B, IC50 = 8.8 nmol/L, Cathepin L, IC50 = 11.1 nmol/L). Ref: J. -T. Woo, et al, Biosci., Biotechnol., Biochem., 1995, 59, 350│ C. -M. Yu, et al, J. Antibiot., 1996, 49, 395 O

O

O H N

HO

NH2

N H

O

OH

179 Celenamide E Type: Cinnamic acid amides. C28H25BrN4O7 Amorph. yellow solid (MeOH aq), mp 212–218 °C, [α]D25 = −25.2° (c = 0.25, MeOH). Source: Sponge Cliona chilensis (Patagonia). Pharm: Antibacterial (gram-positive bacteria, 50 μg/disk). Ref: J. A. Palermo, et al, JNP, 1998, 61,488 OH

OH

HO

OH

HO

O H N

H2N

N H O Br N H

1.3 Amide Alkaloids

63

180 Iotrochamide A Type: Cinnamic acid amides. C19H19NO5 Source: Sponge Iotrochota sp. (Curacao I., Queensland, Australia). Pharm: Antitrypanosomal (Trypanosoma brucei, selective, moderate). Ref: Y. Feng, et al, BoMCL, 2012, 22, 4873 O

HO

HO

O N H O

181 Iotrochamide B Type: Cinnamic acid amides. C21H19BrN2O4 Source: Sponge Iotrochota sp. (Curacao I., Queensland, Australia). Pharm: Antitrypanosomal (Trypanosoma brucei, selective, moderate). Ref: Y. Feng, et al, BoMCL, 2012, 22, 4873 Br

COOH O HN

N H O

182 Namalide Type: Cinnamic acid amides. C31H41N5O6 Source: Lithistid sponge Siliquariaspongia mirabilis (Nama I., Chuuk Lagoon, Federated States of Micronesia). Pharm: Carboxypeptidase A inhibitor. Ref: P. Cheruku, et al, JMC, 2012, 55, 735 O H N

H N N H O

COOH

O

NH NH O

183 Aplaminal Type: Cyclolactams. C16H19N3O5 Plates (MeOH), mp 235–237 °C, [α]D20 = −133° (c = 0.02, MeOH). Source: Sea hare Aplysia kurodai. Pharm: Cytotoxic (HeLa-S3, IC50 = 0.51 μg/mL). Ref: T. Kuroda, et al, Org. Lett., 2008, 10, 489

64

1 Amine Guanidine and Amide Alkaloids

O N

N NH

O O

O O

184 Bengamide A Type: Cyclolactams. C31H56N2O8 Cryst. (MeOH), mp 114–115 °C, [α]D20 = +30.3° (c = 0.081, MeOH). Source: Sponges Stelletta splendens (Fiji, 1996), Stelletta sp. (Jamieson Reef, Bonaparte Archipelago, Australia), Jaspis cf. coriacea (Fiji), Jaspis sp. (Australia), Jaspis carteri and Pachastrissa sp. Pharm: Cytotoxic (P388, GI50 = 0.12 μg/mL; OVCAR-3, GI50 = 0.01 μg/mL; NCI-H460, GI50 = 0.00054 μg/mL; KM20L2, GI50 = 0.0049 μg/mL; DU145, GI50 = 0.0.0056 μg/mL; BXPC3, GI50 = 0.027 μg/mL; SF295, GI50 = 0.001 μg/mL); cytotoxic (SF268, GI50 < 0.02 μmol/L; MCF7, GI50 < 0.02 μmol/L; H460, GI50 < 0.02 μmol/L; HT29, GI50 < 0.02 μmol/L; normal mammalian cell line CHO-K1, GI50 = 0.1 μmol/L); cytotoxic (NCI’s Development Therapeutics Program 60 cells assay, NSCL: A549, IC50 = 0.019 μmol/L; HOP-92, IC50 = 0.200 μmol/L; NCI-H522, IC50 = 0.060 μmol/L; colon: HCT116, IC50 = 0.018 μmol/L; HCT15, IC50 = 0.260 μmol/L; Colon205, IC50 = 0.018 μmol/L; CNS: SNB75, IC50 = 0.190 μmol/L; SNB19, IC50 = 0.024 μmol/L; melanoma: UACC62, IC50 = 0.015 μmol/L; LOX-IMVI, IC50 = 0.023 μmol/L; MALME-3M, IC50 = 0.180 μmol/L; ovarian: OVCAR-3, IC50 = 0.010 μmol/L; OVCAR-8, IC50 = 0.007 μmol/L; renal: UO-31, IC50 = 0.370 μmol/L; 786–0, IC50 = 0.024 μmol/L; leukemia: CCRF-CEM, IC50 = 0.027 μmol/L; average IC50 = (0.046 ± 0.005)μmol/L); cytotoxic (using COMPARE algorithm to analyze, data suggests bengamide cytotoxicity is not correlated with any of reported molecular targets, bengamides activity may be due to inhibition of a novel target); anthelminthic (in vitro, 0.1 μmol/L); antiproliferative (MDA-MB435, IC50 = (0.001 ± 0.0006)μmol/L); antimicrobial; antiparasitic. Ref: E. Quiñoà, et al, JOC, 1986, 51, 4494│ A. Groweiss, et al, JNP, 1999, 62, 1691│ Z. Thale, et al, JOC, 2001, 66, 1733│ G. R. Pettit, et al, JNP, 2008, 71, 438│ S. P. B. Ovenden, et al, Mar. Drugs, 2011, 9, 2469 OH

1

O

4

9

O

H H N

H 16

2 10

OH

OH

O

13

O O

N

1.3 Amide Alkaloids

65

185 Bengamide B Type: Cyclolactams. C32H58N2O8 Viscous oil, [α]D20 = +34.6° (c = 0.075, MeOH). Source: Sponges Jaspis cf. coriacea (Fiji), Jaspis sp. (Australia) and Pachastrissa sp. Pharm: Cytotoxic (NCI’s Development Therapeutics Program 60 cells assay, NSCL: A549, IC50 = 0.0019 μmol/L; HOP-92, IC50 = 0.0068 μmol/L; NCI-H522, IC50 = 0.0063 μmol/L; colon: HCT116, IC50 = 0.0024 μmol/L; HCT15, IC50 = 0.130 μmol/L; Colon205, IC50 = 0.025 μmol/L; CNS: SNB75, IC50 = 0.063 μmol/L; SNB19, IC50 = 0.0086 μmol/L; melanoma: UACC62, IC50 = 0.0052 μmol/L; LOX-IMVI, IC50 = 0.0023 μmol/L; MALME-3M, IC50 = 0.022 μmol/L; ovarian: OVCAR-3, IC50 = 0.010 μmol/L; OVCAR-8, IC50 = 0.0051 μmol/L; renal: UO-31, IC50 = 0.025 μmol/L; 786–0, IC50 = 0.0035 μmol/L; leukemia: CCRF-CEM, IC50 = 0.027 μmol/L; average IC50 = (0.011 ± 0.001)μmol/L); antiproliferative (MDA-MB-435 cells, IC50 = (0.012 ± 0.003)μmol/L); anthelminthic; antiparasitic; antimicrobial. Ref: E. Quiñoà, et al, JOC, 1986, 51, 4494│ A. Groweiss, et al, JNP, 1999, 62, 1691│ Z. Thale, et al, JOC, 2001, 66, 1733│ F. R. Kinder, et al, JOC, 2001, 66, 2118 OH

1

O

4

9

O

H

H N

N

16

2 10

OH

OH

O

13

O O

186 Bengamide C Type: Cyclolactams. C28H48N2O12 Unstable in CDCl3 solution. Source: An unidentified sponge (family Jaspidae). Pharm: Anthelmintic; nematocide. Ref: E. Quiñoà, et al, JOC, 1986, 51, 4494│ M. Adamczeski, et al, JACS, 1989, 111, 647│ M. Adamczeski, et al, JOC, 1990, 55, 240 O

O

OH

H N

5'

OH

OH

O O

OH 5R

6S 3R

4S

OH

H N

O 2R

OH

O

187 Bengamide D Type: Cyclolactams. C29H50N2O2 [α]D20 = +19.8° (c = 0.086, MeOH), Unstable in CDCl3 solution. Source: An unidentified sponge (family Jaspidae). Pharm: Anthelmintic; nematocide. Ref: E. Quiñoà, et al, JOC, 1986, 51,

66

1 Amine Guanidine and Amide Alkaloids

4494│ M. Adamczeski, et al, JACS, 1989, 111, 647│ M. Adamczeski, et al, JOC, 1990, 55, 240 O

OH

O H N

5'

O OH

OH

OH

5R

N 6

O 3R

O

4S

OH

2R

OH

O

188 Bengamide E Type: Cyclolactams. C17H30N2O6 [α]D22 = +24° (c = 0.1, MeOH); [α]D20 = +36.9° (c = 0.043, MeOH). Source: Sponges Jaspis cf. coriacea (Fiji) and Pachastrissa sp. Pharm: Anthelminthic (in vitro, 0.1 μmol/L); antiproliferative (MDA-MB-435, IC50 = (3.3 ± 1.2)μmol/L). Ref: M. Adamczeski, et al, JACS, 1989, 111, 647│ J. A. Marshall, et al, JOC, 1993, 58, 6229│ C. Mukai, et al, Tet. Lett., 1994, 35, 6899│ N. Chida, et al, Heterocycles, 1994, 38, 2383│ F. R. Kinder, et al, JOC, 2001, 66, 2118

O

OH

O H N

OH

OH

H N

O

189 Bengamide F Type: Cyclolactams. C18H32N2O6 Colourless oil, [α]D20 = +27.9° (c = 0.039, MeOH). Source: Sponges Jaspis cf. coriacea (Fiji), Stelletta sp. (Jamieson Reef, Bonaparte Archipelago, Australia) and Jaspis cf. coriacea. Pharm: Cytotoxic (SF268, GI50 = 1.8 μmol/L; MCF7, GI50 = 0.7 μmol/L; H460, GI50 = 0.6 μmol/L; HT29, GI50 = 1.5 μmol/L; CHO-K1, GI50 = 32 μmol/L); anthelminthic (in vitro, 0.1 μmol/L; in vivo); antiproliferative (MDA-MB-435, IC50 = (2.9 ± 2.9)μmol/L). Ref: M. Adamczeski, et al, JOC, 1990, 55, 240│ Z. Thale, et al, JOC, 2001, 66, 1733│ S. P. B. Ovenden, et al, Mar. Drugs, 2011, 9, 2469 OH

O

O H N

OH

OH

O

N

1.3 Amide Alkaloids

67

190 Bengamide G Type: Cyclolactams. C30H54N2O8 [α]D25 = +14.0° (c = 0.1, MeOH). Source: Sponges Jaspis carteri (New Caledonia) and Jaspis cf. coriacea (Fiji). Pharm: Antiproliferative. Ref: Z. Thale, et al, JOC, 2001, 66, 1733│ M. V. D’Auria, et al, JNP, 1997, 60, 814 OH

O

O H N

OH

OH

H N O

O O

191 Bengamide M Type: Cyclolactams. C33H60N2O8 Oil, [α]D = +2.1° (c = 61.9, MeOH). Source: Sponge Jaspis cf. coriacea (Fiji). Pharm: Antiproliferative (MDA-MB-435, IC50 = (0.0101 ± 0.0021)μmol/L). Ref: Z. Thale, et al, JOC, 2001, 66, 1733 OH

O

O

H N

N OH

OH

O O 11

O

192 Bengamide N Type: Cyclolactams. C31H56N2O8 Colourless oil, [α]D = +20.7°. Source: Sponge Stelletta sp. (Jamieson Reef, Bonaparte Archipelago, Australia). Pharm: Cytotoxic (SF268, GI50 < 0.02 μmol/L; MCF7, GI50 < 0.02 μmol/L; H460, GI50 < 0.02 μmol/L; HT29, GI50 < 0.02 μmol/L; CHO-K1, GI50 = 0.2 μmol/L). Ref: Z. Thale, et al, JOC, 2001, 66, 1733│ S. P. B. Ovenden, et al, Mar. Drugs, 2011, 9, 2469 OH

O

O H N

OH

OH

H N O

O O

9

68

1 Amine Guanidine and Amide Alkaloids

193 Bengamide O Type: Cyclolactams. C32H58N2O8 Oil, [α]D = +35.8° (c = 23.9, MeOH). Source: Sponge Jaspis cf. coriacea (Fiji). Pharm: Antiproliferative (MDA-MB-435, IC50 = (0.00029 ± 0.0005)μmol/L). Ref: Z. Thale, et al, JOC, 2001, 66, 1733 O

OH

O

H N

N OH

OH

O O 10

O

194 Bengamide P Type: Cyclolactams. C31H56N2O7 Oil, [α]D = +47.2° (c = 3.6, MeOH). Source: Sponge Jaspis cf. coriacea (Fiji). Pharm: Cytotoxic (NCI’s Development Therapeutics Program 60 cells assay, NSCL: A549, IC50 = 0.69 μmol/L; HOP-92, IC50 = 5.6 μmol/ L; NCI-H522, IC50 = 3.1 μmol/L; colon: HCT116, IC50 = 0.73 μmol/L; HCT15, IC50 = 2.80 μmol/L; Colon205, IC50 = 0.30 μmol/L; CNS: SNB75, IC50 = 3.3 μmol/L; SNB19, IC50 = 5.4 μmol/L; melanoma: UACC62, IC50 = 2.5 μmol/L; LOX-IMVI, IC50 = 1.1 μmol/L; MALME-3M, IC50 = 6.0 μmol/L; ovarian: OVCAR-3, IC50 = 4.0 μmol/L; OVCAR-8, IC50 = 1.9 μmol/L; renal: UO-31, IC50 = 0.990 μmol/L; 786–0, IC50 = 0.940 μmol/L; leukemia: CCRF-CEM, IC50 = 3.10 μmol/L; average IC50 = (2.70 ± 0.23)μmol/L); anthelminthic (in vitro, 0.1 μmol/L); antiproliferative (MDA-MB-435 cells, IC50 = (1.2 ± 7.9)μmol/L). Ref: Z. Thale, et al, JOC, 2001, 66, 1733 O

OH

H N

O NH

O

O

OH

O

11

195 Bengamide Q Type: Cyclolactams. C32H58N2O7 Oil, [α]D = +14.1° (c = 10.7, MeOH). Source: Sponge Jaspis cf. coriacea (Fiji). Pharm: Anthelminthic (in vitro, 0.1 μmol/L). Ref: Z. Thale, et al, JOC, 2001, 66, 1733

1.3 Amide Alkaloids

OH

O

69

O

H N

N O

OH

O

O

11

196 Bengamide Y Type: Cyclolactams. C17H30N2O7 Colourless oil, [α]D = +14° (c = 0.11, MeOH). Source: Sponges Stelletta sp. (Jamieson Reef, Bonaparte Archipelago, Australia) and Jaspis cf. coriacea (Fiji). Pharm: Cytotoxic (SF268, GI50 = 72 μmol/L; MCF7, GI50 = 52 μmol/ L; H460, GI50 = 25 μmol/L; HT29, GI50 = 48 μmol/L; CHO-K1, GI50 > 184 μmol/L); cytotoxic (CNS SNB19, IC50 = 0.68 μg/mL, HCT116, IC50 = 0.8 μg/mL, LOX, IC50 = 4.4 μg/mL, NSCLC A549, IC50 = 4.8 μg/mL, OVCAR-3, IC50 = 4.6 μg/mL, UO-31, IC50 = 9.9 μg/mL); cytotoxic (panel of hmn tumour cell lines: CNS SNB75 cells, IC50 > 40 μg/mL; CNS SNB19 cells, IC50 = 0.68 μg/mL; HCT116, IC50 = 0.8 μg/mL; HCT15, IC50 > 40 μg/mL; LOX, IC50 = 4.4 μg/mL; MALME-3, IC50 > 40 μg/mL; NSCLC A549, IC50 = 4.8 μg/mL; NSCLC HOP-92, IC50 > 40 μg/mL; OVCAR-3, IC50 = 4.6 μg/mL; UO-31, IC50 = 9.9 μg/mL); antiproliferative. Ref: A. Groweiss, et al, JNP, 1999, 62, 1691│ Z. Thale, et al, JOC, 2001, 66, 1733│ S. P. B. Ovenden, et al, Mar. Drugs, 2011, 9, 2469 OH

O

O H N

OH

OH

H N

O OH

197 Bengamide Z Type: Cyclolactams. C18H32N2O7 [α]D20 = +45° (c = 0.11, MeOH). Source: Sponges Jaspis sp. (Australia) and Jaspis cf. coriacea (Fiji). Pharm: Cytotoxic (panel of hmn tumour cell lines: SNB75, IC50 > 40 μg/mL; SNB19, IC50 = 0.56 μg/mL; HCT116, IC50 = 4.0 μg/mL; HCT15, IC50 > 40 μg/mL; LOX, IC50 = 2.1 μg/mL; MALME-3, IC50 > 40 μg/mL; NSCLC A549, IC50 = 4.1 μg/mL; NSCLC HOP-92, IC50 > 40 μg/mL; OVCAR3, IC50 = 0.52 μg/mL; UO-31, IC50 = 7.2 μg/mL); anthelmintic; nematocide; antiproliferative. Ref: A. Groweiss, et al, JNP, 1999, 62, 1691

70

1 Amine Guanidine and Amide Alkaloids

OH

1

O

O

4

9

H N

H 16

2

N

10

OH

OH

O

13

OH

198 Bisucaberin Type: Cyclolactams. C18H32N4O6 Cryst., mp 180 °C (dec). Source: Marine-derived bacteria Alteromonas haloplanktis and Vibrio salmonicida. Pharm: Siderophore which sensitizes tumour cells to macrophage-mediated cytolysis. Ref: T. Kameyama, et al, J. Antibiot., 1987, 40, 1664; 1671 HO N O

NH O O O

HN N OH

199 7-Bromocavernicolenone Type: Cyclolactams. C8H8BrNO4 Needles (MeOH), mp 165–170 °C (dec). Source: Sponge Aplysina cavernicola [Syn. Verongia cavernicola] (Mediterranean). Pharm: Antibacterial. Ref: M. D’Ambrosio, et al, Helv. Chim. Acta, 1985, 68, 1453 O Br

OH NH O OH

200 Caprolactin A Type: Cyclolactams. C15H28N2O2 [α]D22 = +5.4° (c = 1.03, CH2Cl2) (mixture with Caprolactin B). Source: An unidentified marine bacterium (gram-positive, psychrophilic, cold water, depth of 5000 m, sediment sample). Pharm: Cytotoxic (KB, MIC = 10 μg/mL; LoVo, MIC = 5 μg/mL); antiviral (HSV-2 virus, MIC = 100 μg/mL). Ref: B. S. Davidson et al, Tetrahedron, 1993, 49, 6569│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)

1.3 Amide Alkaloids

71

O H N HN O

201 Caprolactin B Type: Cyclolactams. C15H28N2O2 [α]D22 = +5.4° (c = 1.03, CH2Cl2) (mixture with Caprolactin A). Source: An unidentified marine bacterium (gram-positive, psychrophilic, cold water, depth of 5000 m, sediment sample). Pharm: Cytotoxic (KB, MIC = 10 μg/mL; LoVo, MIC = 5 μg/mL); antiviral (HSV-2 virus, MIC =100 μg/mL). Ref: B. S. Davidson et al, Tetrahedron, 1993, 49, 6569│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) O H N HN O

202 Cephalimysin A Type: Cyclolactams. C22H25NO6 Pale yellow oil, [α]D = = 3.5° (c = 0.11, EtOH). Source: Marine-derived fungus Aspergillus fumigatus from fish Mugil cephalus. Pharm: Cytotoxic (P388 and HL60, significant). Ref: T. Yamada, et al, Tet. Lett., 2007, 48, 6294 O OH

O

O NH

O O

203 Cephalimysin C Type: Cyclolactams. C22H21NO7 Source: Marine-derived fungus Aspergillus fumigatus from fish Mugil cephalus (Katsuura Bay, Japan). Pharm: Cytotoxic (P388 and HL60, moderate). Ref: T. Yamada, et al, JOC, 2010, 75, 4146

72

1 Amine Guanidine and Amide Alkaloids

O OH O

OO

O N H

O

204 Cephalimysin D Type: Cyclolactams. C22H21NO7 Source: Marine-derived fungus Aspergillus fumigatus from fish Mugil cephalus (Katsuura Bay, Japan). Pharm: Cytotoxic (P388 and HL60, moderate). Ref: T. Yamada, et al, JOC, 2010, 75, 4146

O OH O

OO

O N H

O

205 Ceratamine A Type: Cyclolactams. C17H16Br2N4O2 Yellow cryst. (MeOH), mp 236 °C. Source: Sponge Pseudoceratina sp. Pharm: Antimitotic. Ref: E. Manzo, et al, Org. Lett., 2003, 5, 4591 Br O

O

Br N

N

6

H N

N

206 Heronamide C Type: Cyclolactams. C29H39NO3 Powder, [α]D20 = +151° (c = 0.1, MeOH). Source: Marine-derived streptomycete Streptomyces sp. CMB-M0406 (sediment, Heron Is., Australia). Pharm: Pronounced, reversible and non-cytotoxic effect on mammalian cell morphology. Ref: R. Raju, et al, Org. Biomol. Chem., 2010, 8, 4682│ R. Sugiyama, et al, Tet. Lett., 2013, 54, 1531 (configuration needed reassignment).

1.3 Amide Alkaloids

73

NH

HO O

OH

configuration needed reassignmeht

207 Isobengamide E Type: Cyclolactams. C17H30N2O6 Oil, [α]D20 = +17.1° (c = 0.052, MeOH). Source: An unidentified sponge (Jaspidae, Fiji). Pharm: Anthelmintic; nematocide. Ref: M. Adamczeski, et al, JACS, 1989, 111, 647│ M. Adamczeski, et al, JOC, 1990, 55, 240 H 2N

O

OH

O

OH

N O

OH

208 Phenethyl 5-oxo-L-prolinate Type: Cyclolactams. C13H15NO3 Source: Deep-sea fungus Aspergillus versicolor ZBY-3. Pharm: Cytotoxic (K562, 100 μg/mL). Ref: Y. Dong, et al, Mar. Drugs, 2014, 12, 4326 O

O

H HN

O

209 2,3,4,5-Tetrahydro-3,5-dihydroxy-6H-1,5-benzoxazocin-6-one Type: Cyclolactams. C10H11NO4 Pale yellow solid, [α]D20 = +15.8° (c = 0.4, MeOH). Source: An unidentified marine-derived bacterium. Pharm: Siderophore. Ref: M. -X. You, et al, Chin. J. Chem., 2008, 26, 1332 O

OH

N O

OH

74

1 Amine Guanidine and Amide Alkaloids

210 o-Aminophenol Type: Phenylamine alkaloids. C6H7NO Cryst. (H2O), mp 174 °C, sol. MeOH, H2O, Et2O, EtOAc; fairly sol. CCl4; poorly sol. hexane, pKa1 4.78 (20 °C) pKa2 9.97 (20 °C). Source: An unidentified marine-derived purpre bacterium from sponge Adocia sp. Pharm: Antimicrobial. Ref: J. M. Oclarit, et al, Fisheries Science, 1994, 60, 559 OH 1

NH2 2

2 Phenylamine and Phenethylamine Amines 2.1 Phenylamine Alkaloids 211 5-Dodecenyl-4-amino-3-hydroxybenzoate Antibiotic B 5354A Type: Phenylamine alkaloids. C19H29NO3 Source: Marine-derived bacterium Ruegeria sp. SANK 71896. Pharm: Sphingosine kinase inhibitor. Ref: K. Kono, et al, J. Antibiot., 2000, 53, 753 NH2 OH

O

O

5

4

212 Dysidine (2001) Type: Phenylamine alkaloids. C23H33NO3S Deep purple cryst., [α]D25 = +19° (c = 1, MeOH). Source: Sponge Dysidea sp. (Vanuatu). Pharm: PTP1B inhibitor (IC50 = 6.7 mmol/L); PLA2 inhibitor (selective). Ref: C. Giannini, et al, JNP, 2001, 64, 612│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev) OH H O

O HN

O S

OH

O

213 MD113068-6 Type: Phenylamine alkaloids. C11H11NO3 Source: Deep-sea fungus Penicillium paneum SD-44 (sediment). Pharm: Cytotoxic (HeLa, IC50 = 6.6 μmol/L; control Fluorouracil, IC50 = IC50 = 14.5 μmol/L). Ref: C. Li, et al, Mar. Drugs, 2013, 11, 3068 O

OH O N

https://doi.org/10.1515/9783110655193-002

76

2 Phenylamine and Phenethylamine Amines

214 Penipacid A Type: Phenylamine alkaloids. C13H18N2O3 Yellowish solid. Source: Deep-sea fungus Penicillium paneum SD-44 (sediment). Pharm: Cytotoxic (RKO cell line, IC50 = 8.4 μmol/L; control Fluorouracil, IC50 = 25.0 μmol/L). Ref: C. Li, et al, Mar. Drugs, 2013, 11, 3068 O

OH H N

OH N

215 Penipacid E Type: Phenylamine alkaloids. C12H10N2O3 Yellowish solid. Source: Deep-sea fungus Penicillium paneum SD-44 (sediment). Pharm: Cytotoxic (RKO cell line, IC50 = 9.7 μmol/L; control Fluorouracil, IC50 = 25.0 μmol/L). Ref: C. Li, et al, Mar. Drugs, 2013, 11, 3068 O

OH H N

N O

216 2,7-Tetradecadienyl-4-amino-3-hydroxybenzoate Antibiotic B 5354B Type: Phenylamine alkaloids. C21H31NO3 Source: Marine-derived bacterium Ruegeria sp. SANK 71896. Pharm: Sphingosine kinase inhibitor. Ref: K. Kono, et al, J. Antibiot., 2000, 53, 753 NH2 OH

O

O

5

217 7Z-Tetradecenyl-4-amino-3-hydroxybenzoate Antibiotic B 5354C Type: Phenylamine alkaloids. C21H33NO3 Powder. Source: Marine-derived bacterium Ruegeria sp. SANK 71896. Pharm: Sphingosine kinase inhibitor. Ref: K. Kono, et al, J. Antibiot., 2000, 53, 753

2.2 Simple Tyramine Alkaloids

77

NH2 OH

O

O

2.2 Simple Tyramine Alkaloids 218 N-Acetyltyramine Type: Simple tyramine alkaloids. C10H13NO2 mp 134–135 °C, sinters at 128 °C. Source: Marine-derived fungus Aspergillus fumigatus from sediments (China). Pharm: Cytotoxic (SRB assay, K562, IC50 = 17.4 μmol/L); cytotoxic (A375, K562); antifungal (Cladosporium sphaerospermum); L-1R antagonist; factor XIIIa inhibitor. Ref: M. Kanou, et al, JP 10259174, 1998│ X. F. Meng, et al, Chinese Journal of Antibiotics, 1998, 23, 271│ W. S. Garcez, et al, J. Agric. Food Chem., 2000, 48, 3662│ K. P. Du, et al, Chinese Journal of Antibiotics, 2001, 26, 410│ W. Y. Zhao, et al, Nat. Prod. Res., 2010, 24, 953 O NH

HO

219 4- (2-Aminoethyl)-2-bromophenol Type: Simple tyramine alkaloids. C8H10BrNO Cryst., mp 162–164 °C Source: Ascidian Cnemidocarpa bicornuta (New Zealand). Pharm: Cytotoxic (P388, IC50 = 46 μmol/L). Ref: B. S. Lindsay, et al, JNP, 1998, 61, 857 Br

NH2

HO

220 Aplaminone Type: Simple tyramine alkaloids. C26H40BrNO3 Oil, [α]D23 = −2.9° (c = 1.18, MeOH). Source: Sea hare Aplysia kurodai. Pharm: Cytotoxic (HeLa-S3, IC50 = 0.28 μg/mL). Ref: H. Kigoshi, et al, Tet. Lett., 1990, 31, 4911│ H. Kigoshi, et al, Tet. Lett., 1992, 33, 4195

78

2 Phenylamine and Phenethylamine Amines

O OH

Br 3

N 9'

11'

O

221 Aplysamine 6 Type: Simple tyramine alkaloids. C21H23Br3N2O3 Gum. Source: Sponge Pseudoceratina sp. Pharm: Isoprenylcysteine carboxyl methyltransferase inhibitor. Ref: M. S. Buchanan, et al, JNP, 2008, 71, 1066 Br O H N

Br

O O

NH2

Br

222 Convolutamine A Type: Simple tyramine alkaloids. C13H18Br3NO2 Oil. Source: Bryozoan Amathia convoluta (Florida). Pharm: Cytotoxic (P388, L1210, KB). Ref: H. -P. Zhang, et al, Chem. Lett., 1994, 2271│ H. Zhang, et al, Tetrahedron, 1994, 50, 10201│ Y. Kamono, et al, Collect. Czech. Chem. Commun., 1999, 64, 1147│ H. Hashima, et al, BoMC, 2000, 8, 1757 O Br

Br 4

N Br

OH

223 Convolutamine B Type: Simple tyramine alkaloids. C13H19Br2NO2 Oil. Source: Bryozoan Amathia convoluta (Florida). Pharm: Cytotoxic (P388, L1210, KB). Ref: H. Zhang, et al, Chem. Lett., 1994, 2271│ H. Zhang, et al, Tetrahedron, 1994, 50, 10201

2.2 Simple Tyramine Alkaloids

79

O Br

N OH

Br

224 Convolutamine C Type: Simple tyramine alkaloids. C12H16Br3NO2 Oil. Source: Bryozoan Amathia convoluta (Florida). Pharm: Cytotoxic (P388, L1210, KB). Ref: H. Zhang, et al, Chem. Lett., 1994, 2271│ H. Zhang, et al, Tetrahedron, 1994, 50, 10201│ Y. Kamono, et al, Collect. Czech. Chem. Commun., 1999, 64, 1147│ H. Hashima, et al, BoMC, 2000, 8, 1757 O Br

Br

N H OH

Br

225 Convolutamine F Type: Simple tyramine alkaloids. C10H12Br3NO Oil, [α]D20 = +24.3° (c = 0.4, CHCl3). Source: Bryozoan Amathia convoluta (Florida). Pharm: Cytotoxic (KB, IC50 = 27 μg/mL, and its vincristine-resistant KB/VJ-300 cells, IC50 = 9.6 μg/mL, U937, IC50 = 13 μg/mL); inhibits cell division (fertilized sea urchin eggs, IC50 = 82 μg/mL). Ref: H. -P. Zhang, et al, Chem. Lett., 1994, 2271│ Y. Kamono, et al, Collect. Czech. Chem. Commun., 1999, 64, 1147│ H. Hashima, et al, BoMC, 2000, 8, 1757 O Br

Br

N H Br

226 (3,5-Di-iodo-4-methoxyphenyl)ethylamine Type: Simple tyramine alkaloids. C9H11I2NO Cryst. (petrol), mp 55–57 °C. Source: Ascidian Didemnum sp. (Guam). Pharm: Cytotoxic (mildly), antifungal. Ref: D. F. Sesin, et al, Tet. Lett., 1984, 25, 403 I NH2

O

I

80

2 Phenylamine and Phenethylamine Amines

227 Dopamine Hydroxytyramine Type: Simple tyramine alkaloids. C8H11NO2 Source: Green alga Monostroma fuscum, marine animals e.g. sea anemone Metridium senile; occurs in animals (esp. in the brain and nervous system) and in several higher plants, such as broom (Cytisus scoparius), banana (Musa sapientum) and Hermidium alipes (preferred genus name Mirabilis). Pharm: Adrenergic; sympathomimetic; central neurotransmitter and precursor of noradrenaline; antiparkinsonian; cardiotonic; antihypotensive; LD50 (rat, ipr) = 163 mg/kg. Ref: R. D. Tocher, et al, Can. J. Bot., 1966, 44, 605│ P. M. Lenicque, et al, Comp. Biochem. Physiol., C: Comp. Pharmacol., 1977, 56, 31│ CNS Neurotransmitters and Neuromodulators: Dopamine, 1996, ed. T.W. Stone, CRC Press NH2

HO

HO

228 Hermitamide A Type: Simple tyramine alkaloids. C23H37NO2 Pale yellow oil, [α]D26 = −9.3° (c = 0.45, CHCl3). Source: Cyanobacterium Lyngbya majuscula (Papua New Guinea). Pharm: Anticancer-Cell-Effect (model: human HEK embryonic kidney cells, mechanism: voltage-gated sodium channel inhibition) (De Oliveira, 2011); cytotoxic (Neuro-2a neuroblastoma cells in tissue culture, IC50 = 2.2 μg/mL); toxic (brine shrimp and goldfish); LD50 (brine shrimp Artemia salina bioassay) = 5 μmol/L; ichthyotoxic (goldfish, LD50 = 19 μmol/L). Ref: T. Tan, et al, JNP, 2000, 63, 952│ E. O. De Oliveira, et al, BoMC 2011, 19, 4322 H N

7S

O

O

229 Hordenine Type: Simple tyramine alkaloids. C10H15NO mp 118 °C, bp11mmHg 173–174 °C. Source: Red alga Phyllophora nervosa, very wide range of plant spp. Pharm: Antihypotensive (in large doses); diuretic, used for treatment of dysentery. Ref: K. C. Güven, et al, Phytochemistry, 1970, 9, 1893

N

HO

2.2 Simple Tyramine Alkaloids

81

230 N-[2-(4-Hydroxy-3-methoxyphenyl)ethyl]-3-methyl-2-dodecenamide Type: Simple tyramine alkaloids. C22H35NO3 Oil which slowly solidifies. Source: Soft coral Sinularia flexibilis. Pharm: Anti-inflammatory; cardiotoxic. Ref: R. Kazlauskas, et al, Aust. J. Chem., 1980, 33, 1799 2''

H N

3''

O

HO

3

O

231 N-[2-(3-Hydroxy-4-methoxyphenyl)ethyl]-3-methyl-2-dodecenamide Type: Simple tyramine alkaloids. C22H35NO3 Oil which slowly solidifies. Source: Soft coral Sinularia flexibilis. Pharm: Anti-inflammatory; cardiotoxic. Ref: R. Kazlauskas, et al, Aust. J. Chem., 1980, 33, 1799 2''

H N

O

3''

O 3

OH

232 N-[2-(4-Hydroxyphenyl)ethyl]-3-methyl-2-dodecenamide Type: Simple tyramine alkaloids. C21H33NO2 mp 70–72 °C. Source: Soft coral Sinularia flexibilis, gorgonian Muricea austera. Pharm: Anti-inflammatory; cardiotoxic. Ref: R. Kazlauskas, et al, Aust. J. Chem., 1980, 33, 1799│ J. -H. Sheu, et al, J. Chin. Chem. Soc. (Taipei), 1999, 46, 253│ M. Guttiérez, et al, JNP, 2006, 69, 1379 H N O

HO

233 N- (2-Phenylethyl)-9-hydroxyhexadecacarboxamide Type: Simple tyramine alkaloids. C24H41NO2 White crystalline solid, mp 78 °C, [α]D25 = −2.68° (c = 0.41, CHCl3). Source: Octocoral Telesto riisei (Chuuk Atoll). Pharm: Cytotoxic (P388, mild). Ref: G. K. Liyanage, et al, JNP, 1996, 59, 148│ K. Böröczky, et al, Chem. Biodiversity, 2006, 3, 622 O N H

OH

82

2 Phenylamine and Phenethylamine Amines

234 N- (2-Phenylethyl)-9-oxohexadecacarboxamide Type: Simple tyramine alkaloids. C24H39NO2 White crystalline solid, mp 85 °C. Source: Octocoral Telesto riisei (Chuuk Atoll). Pharm: Cytotoxic (P388, mild). Ref: G. K. Liyanage, et al, JNP, 1996, 59, 148│ K. Böröczky, et al, Chem. Biodiversity, 2006, 3, 622 O

O N H

235 Purealidin G Type: Simple tyramine alkaloids. C14H22Br2N2O Source: Sponge Psammaplysilla purea (Okinawa). Pharm: Na/K-ATPase inhibitor. Ref: M. Tsuda, et al, Tet. Lett., 1992, 33, 2597│ M. Tsuda, et al, JNP, 1992, 55, 1325│ Y. Venkateswarlu, et al, JNP, 1998, 61, 1388; 1999, 62, 893 H N

Br Br

N

O

236 Turbotoxin A Type: Simple tyramine alkaloids. C17H30I2N2O2+ Source: Prosobranch Turbo marmorata (Japan). Pharm: Toxic (mus, ip, LD99 = 1.0 mg/kg). Ref: H. Kigoshi, et al, Tet. Lett., 1999, 40, 5745 +

I

N

O

+

N

I

237 Turbotoxin B Type: Simple tyramine alkaloids. C17H28I2N2O Source: Prosobranch Turbo marmorata (Japan). Pharm: Toxic (mus, ip, LD99 = 4.0 mg/kg). Ref: H. Kigoshi, et al, Tet. Lett., 1999, 40, 5745 +

I

N

O I

+

N H

2.3 Halogenated Tyrosinoids

83

2.3 Halogenated Tyrosinoids 238 Agelorin A Type: Halogenated tyrosinoids. C29H26Br6N4O11 Amorph. off-white powder, [α]D25 = −17.1° (c = 1.26, Me2CO). Source: Sponge Agelas oroides (Tropical marine sponge, Great Barrier Reef, Australia). Pharm: Antibacterial. Ref: G. M. König, et al, Heterocycles, 1993, 36, 1351│ S. Bardhan, et al, Org. Lett., 2006, 8, 927 O

O

Br

Br

Br

Br

2'

2

OH

Br

HO O

H N

N

OH 11

O

OH H N

O

N

17

O

O

Br

239 Agelorin B Type: Halogenated tyrosinoids. C29H26Br6N4O11 Amorph. powder, [α]D25 = +50° (c = 0.27, Me2CO). Source: Sponge Agelas oroides (Tropical marine sponge, Great Barrier Reef, Australia). Pharm: Antibacterial. Ref: G. M. König, et al, Heterocycles, 1993, 36, 1351│ S. Bardhan, et al, Org. Lett., 2006, 8, 927 O

O

Br

Br

Br

Br

2'

2

OH

Br

HO O

H N

N O

OH

O

OH H N

O Br

N O

240 Aplysamine 2 Type: Halogenated tyrosinoids. C23H28Br3N3O4 Pale tan semicryst. solid (hydrochloride), mp 87–88.5 °C (hydrochloride). Source: Sponges Druinella sp. (Fiji), Aplysina sp., Psammaplysilla purpurea and Pseudoceratina purpurea. Pharm: Cytotoxic (A2780, IC50 = 2.83 μg/mL; K562, IC50 = 1.37 μg/mL). Ref: J. N. Tabudravu,et al, JNP, 2002, 65, 1798│ R. Xynas, et al, Aust. J. Chem., 1989, 42, 1427│ M. R. Rao, et al, Ind. J. Chem., Sect. B, 1999, 38, 1301│ A. Kijjoa, et al, Z. Naturforsch., B, 2005, 60, 904

84

2 Phenylamine and Phenethylamine Amines

O Br

N

OH

Br O

N

Br

N H

O

241 Aplysamine 3 Purpuramine H Type: Halogenated tyrosinoids. C21H24Br3N3O4 Amorph. or semicryst. solid. Source: Sponges Suberea sp. (Okinawa) and Psammaplysilla purpurea (Japan). Pharm: Cytotoxic (P388, IC50 = 1 μg/mL; A549, IC50 = 2 μg/mL; HT29, IC50 = 3 μg/mL; KB, IC50 = 5 μg/mL); antibacterial (Staphylococcus aureus, 100 μg/disk, IZD = 10 mm). Ref: J. Jurek, et al, JNP, 1993, 56, 1609│ H. Yagi, et al, Tetrahedron, 1993, 49, 3749│ M. Tsuda, et al, JNP, 2001, 64, 980 Br O O Br

NH2

Br

N H N

O

HO

242 Aplysamine 4 Type: Halogenated tyrosinoids. C21H23Br4N3O4 Semicryst. solid. Source: Sponge Psammaplysilla purpurea (Kinwan Bay, Okinawa). Pharm: Cytotoxic (WST-8 colorimetric assay 48h, HeLa, IC50 = 3.5 μmol/L); cytotoxic (P388, IC50 = 2.5 μg/mL; A549, IC50 = 2.5 μg/mL; HT29, IC50 = 2.5 μg/mL; KB, IC50 = 5 μg/mL); antibacterial (Staphylococcus aureus, 100 μg/disk, IZD = 10 mm). Ref: J. Jurek, et al, JNP, 1993, 56, 1609│ T. Fujiwara, et al, J. Antibiot., 2009, 62, 393 Br O O Br N H

NH2

Br

N

O

HO Br

243 Aplysamine 5 Type: Halogenated tyrosinoids. C36H52Br3N3O5 Gum. Source: Sponge Psammaplysilla purpurea (Hawaii). Pharm: Cytotoxic (P388, IC50 = 10 μg/mL; A549, IC50 =

2.3 Halogenated Tyrosinoids

85

2.5 μg/mL; HT29, IC50 = 2.5 μg/mL; KB, IC50 = 2 μg/mL). Ref: J. Jurek, et al, JNP, 1993, 56, 1609 Br O

H N

O

11

O

Br

Br

N H HO

O

N

244 Aplysamine 7 Type: Halogenated tyrosinoids. C23H28Br3N3O5 Source: Sponge Pseudoceratina verrucosa (Hook Reef Lagoon, Queensland, Australia). Pharm: Cytotoxic (PC3). Ref: T. D. Tran, et al, JNP, 2013, 76, 516 O

Br N

O

Br HO O

Br N H

N HO

245 Bastadin 1 Type: Halogenated tyrosinoids. C34H30Br4N4O8 Foam. Source: Sponge Ianthella basta. Pharm: Antibacterial (gram-positive bacteria, in vitro, potent). Ref: R. Kazlauskas, et al, Tet. Lett., 1980, 21, 2277; R. Kaztauskas, et al, Aust. J. Chem., 1981, 34, 765│ S. Nishiyama, et al, Tet. Lett., 1982, 23, 1281 OH N H N

Br

O HO Br

O

HO

O N H

Br OH

Br

N OH

86

2 Phenylamine and Phenethylamine Amines

246 Bastadin 2 Type: Halogenated tyrosinoids. C34H29Br5N4O8 Foam. Source: Sponge Ianthella basta. Pharm: Antibacterial (gram-positive bacteria, in vitro, potent). Ref: R. Kazlauskas, et al, Tet. Lett., 1980, 21, 2277│ R. Kazlauskas, et al, Aust. J. Chem., 1981, 34, 765│ S. Nishiyama, et al, Tet. Lett., 1982, 23, 1281│ Z. -W. Guo, et al, JOC, 1998, 63, 4269 OH N H N

Br

O HO Br

O

HO

Br OH Br

Br

O N H

N OH

247 Bastadin 3 Type: Halogenated tyrosinoids. C34H30Br4N4O8 Pale yellow foam. Source: Sponge Ianthella basta. Pharm: Antibacterial (gram-positive bacteria, in vitro, potent). Ref: R. Kazlauskas, et al, Aust. J. Chem., 1981, 34, 765│ Z. -W. Guo, et al, JOC, 1998, 63, 4269 Br OH O Br

N H N

HO

OH

HO

OH

N

H N Br O

OH Br

248 Bastadin 4 Cyclobastadin 1 Type: Halogenated tyrosinoids. C34H25Br5N4O8 Yellow needles (DMF), mp 250 °C (dec). Source: Sponges Ianthella basta and Ianthella quadrangulata. Pharm: Cytotoxic (36 different hmn cell lines, mean IC50 = 2.9 μg/mL);

2.3 Halogenated Tyrosinoids

87

cytotoxic (P388, ED50 = 2.0 μg/mL); anti-inflammatory (50 μg/ear, InRt = 89%); antibacterial (gram-positive bacteria). Ref: R. Kazlauskas, et al, Aust. J. Chem., 1981, 34, 765│ E. O. Pordesimo, et al, JOC, 1990, 55, 4704│ H. Greve, et al, JNP, 2008, 71, 309 OH N H N

5 6

Br

O

11

34

O

O HO

Br OH Br

Br 28 30

16

Br

O

20 21

25

N H N HO

249 Bastadin 5 Cyclobastadin 2 Type: Halogenated tyrosinoids. C34H27Br5N4O8 Cryst. (MeCN) (tetraMe ether), mp 262–264 °C (tetra-Me ether). Source: Sponges Ianthella basta and Ianthella quadrangulata. Pharm: Cytotoxic (36 different hmn cell lines, mean IC50 = 2.2 μg/mL); Ca2+-channel agonist (sarcoplasmic reticulum (SR), EC50 = 2.0 μmol/L, Bastadin 5 stimulates release of Ca2+ from SR by binding to RyR1-FKBP12 Ca2+ channel, a tetrameric heterodimeric channel protein (~ 2,000 kDa) that is associated with the smaller 12 kDa immunophilin FKBP12). Ref: R. Kazlauskas, et al, Aust. J. Chem., 1981, 34, 765│ J. Clardy, Proc. Nat. Acad. Sci. U.S.A. 1995, 92, 56│ M. A. Franklin, et al, JNP, 1996, 59, 1121│ M. N. Masuno, et al, Mar. Drugs, 2004, 2, 176│ H. Greve, et al, JNP, 2008, 71, 309 OH N H N

Br

O O O

HO Br Br O N H HO

N

Br OH Br

88

2 Phenylamine and Phenethylamine Amines

250 Bastadin 6 Cyclobastadin 2 Type: Halogenated tyrosinoids. C34H26Br6N4O8 Powder. Source: Sponges Ianthella basta, Ianthella quadrangulata and Psammaplysilla purpurea. Pharm: Cytotoxic (36 different hmn cell lines, mean IC50 = 0.7 μg/mL); cytotoxic (Sup-T1, IC50 = 7.9 × 10−11 mol/L); antiangiogenic. Ref: E. O. Pordesimo, et al, JOC, 1990, 55, 4704│ H. Greve, et al, JNP, 2008, 71, 309 OH N H N

5 6

Br

O

11

34

O

O

Br OH Br

Br HO

Br 28 30

16

Br

O

20 21

25

N H

N HO

251 Bastadin 7 Cyclobastadin 4 Type: Halogenated tyrosinoids. C34H26Br4N4O8 Foam. Source: Sponges Ianthella basta and Ianthella quadrangulata. Pharm: Cytotoxic (36 different hmn cell lines, mean IC50 = 3.2 μg/mL). Ref: R. Kazlauskas, et al, Aust. J. Chem., 1981, 34, 765│ H. Greve, et al, JNP, 2008, 71, 309 OH N 5

H N

6

Br

O 34

11

O

O HO

28 30

16

Br

Br OH Br

O

20 21

25

N H HO

N

2.3 Halogenated Tyrosinoids

89

252 Bastadin 8 Type: Halogenated tyrosinoids. C34H27Br5N4O9 White film. Source: Sponge Ianthella basta. Pharm: Cytotoxic (P388, ED50 = 3.6 μg/mL); anti-inflammatory (50 μg/ear, InRt = 93%). Ref: R. Kazlauskas, et al, Aust. J. Chem., 1981, 34, 765│ S. Miao, et al, JNP, 1990, 53, 1441│ E. O. Pordesimo, et al, JOC, 1990, 55, 4704 OH N 5

H N

6S

Br

O OH 34

11

O

O HO

Br OH Br

Br 28 30

16

Br

O

20 21

25

N H HO

N

253 Bastadin 9‡ Type: Halogenated tyrosinoids. C34H28Br4N4O8 White powder (MeOH aq). Source: Sponge Ianthella basta. Pharm: Cytotoxic (P388, ED50 = 2.7 μg/mL); anti-inflammatory (50 μg/ear, InRt = 94%). Ref: S. Miao, et al, JNP, 1990, 53, 1441│ E. O. Pordesimo, et al, JOC, 1990, 55, 4704 OH N 5

H N

6

Br

O 34

11

O

O HO

Br 28 30

16

O

20 21

25

N H HO

Br OH Br

N

90

2 Phenylamine and Phenethylamine Amines

254 Bastadin 10 Type: Halogenated tyrosinoids. C34H28Br4N4O9 Colorless oil. Source: Sponge Ianthella basta. Pharm: Anti-inflammatory; inosine 5′-phosphate dehydrogenase inhibitor. Ref: E. O. Pordesimo, et al, JOC, 1990, 55, 4704 OH N 5

H N

6

Br

O OH 34

11

O

O

Br OH Br

HO 28 30

16

Br

O

20 21

25

N H HO

N

255 Bastadin 11 Type: Halogenated tyrosinoids. C34H26Br4N4O8 Whitish film. Source: Sponge Ianthella basta. Pharm: Anti-inflammatory. Ref: E. O. Pordesimo, et al, JOC, 1990, 55, 4704 OH N 5

H N

6

Br

O 34

11

O

O HO

Br OH Br

Br 28 30

16

O

20 21

25

N H HO

N

256 Bastadin 12 Type: Halogenated tyrosinoids. C34H27Br5N4O9 Amorph. Source: Sponges Ianthella basta and Ianthella quadrangulata. Pharm: Cytotoxic (Sup-T1, IC50 = 8.01 × 10−9 mol/L); cytotoxic (36 different hmn cell lines, mean IC50 = 1.1 μg/mL). Ref: E. O. Pordesimo, et al, JOC, 1990, 55, 4704│ S. Miao, et al, JNP, 1990, 53,

2.3 Halogenated Tyrosinoids

91

1441│ A. V. Reddy, et al, BoMC, 2006, 14, 4452│ H. Greve, et al, JNP, 2008, 71, 309 OH N H N

5 6

Br

O 34

11

O

O HO

Br OH Br

Br 28 30

16

O

20 21

25

N H HO

N

257 Bastadin 13 Type: Halogenated tyrosinoids. C34H28Br4N4O8 Powder, mp 177–179 °C. Source: Sponges Ianthella quadrangulata and Ianthella basta. Pharm: Cytotoxic (36 different hmn cell lines, mean IC50 = 2.4 μg/mL). Ref: H. Greve, et al, JNP, 2008, 71, 309│ J. R. Carney, et al, JNP, 1993, 56, 153 OH N 5

H N

6

Br

O OH 34

11

O

O HO

28 30

16

Br

Br OH Br

O

20 21

25

N H HO

N

258 Bastadin 14 Isobastadin 4 Type: Halogenated tyrosinoids. C34H25Br5N4O8 Source: Sponge Psammaplysilla purpurea (Pohnpei). Pharm: Cytotoxic (Sup-T1, IC50 = 1.4 × 10−7 mol/L); dehydrofolate reductase inhibitor (IC50 = 2.5 μg/mL); topoisomerase II inhibitor (IC50 = 2.0 μg/mL). Ref: J. R. Carney,et al, JNP, 1993, 56, 153│ A. V. Reddy, et al, BoMC, 2006, 14, 4452│ H. Greve, et al, JNP, 2008, 71, 309

92

2 Phenylamine and Phenethylamine Amines

OH N H N

5 6

Br

O 34

11

O

O HO

Br OH Br

Br 28 30

16

O

20 21

25

N H HO

N

259 Bastadin 15 Type: Halogenated tyrosinoids. C34H27Br5N4O8 Source: Sponge Ianthella sp. (New South Wales). Pharm: Cytotoxic (Sup-T1, IC50 = 6.45 × 10−7 mol/L). Ref: A. F. Dexter, et al, JNP, 1993, 56, 782│ A. V. Reddy, et al, BoMC, 2006, 14, 4452 OH N 5

H N

6

Br

O

11

34

O

O HO

28 30

16

Br

Br OH Br

Br

O

20 21

25

N H N HO

260 Bastadin 16 Type: Halogenated tyrosinoids. C34H27Br5N4O8 Source: Sponges Ianthella basta (Sulawesi, Indonisia) and Psammaplysilla purpurea. Pharm: Cytotoxic (Sup-T1, IC50 = 1.0 × 10−12 mol/L). Ref: S. K. Park, et al, JNP, 1994, 57, 407│ A. V. Reddy, et al, BoMC, 2006, 14, 4452

2.3 Halogenated Tyrosinoids

93

OH N H N

Br

O O Br

O

Br OH

HO

Br

Br

O N H N OH

261 (E,E)-Bastadin 19 Type: Halogenated tyrosinoids. C34H27Br5N4O8 Source: Sponges Ianthella basta and Ianthella cf. reticulata (Milne Bay, Papua New Guinea). Pharm: Cytotoxic (Sup-T1, IC50 = 7.3 × 10−8 mol/L); Calcium channel modulator. Ref: A. V. Reddy, et al, BoMC, 2006, 14, 4452│ L. Calcul, et al, JNP, 2010, 73, 365 OH N H N

E

O

Br 9

34

Br

HO

O OH Br

O

Br 28

Br

O 24

N H

E

N OH

262 Bastadin 20 Type: Halogenated tyrosinoids. C34H28Br4N4O8 Solid. Source: Sponge Ianthella basta. Pharm: Ca2+channel agonist (sarcoplasmic reticulum, EC50 = 20.6 μmol/L). Ref: M. A. Franklin, et al, JNP, 1996, 59, 1121

94

2 Phenylamine and Phenethylamine Amines

OH N H N O

Br 9

34

Br

HO

O OH

O

Br 28

Br

O 24

N H N OH

263 Bastadin 21 Type: Halogenated tyrosinoids. C34H29Br3N4O8 Amorph. solid. Source: Sponge Ianthella quadrangulata. Pharm: Cytotoxic (36 different hmn cell lines, mean IC50 = 8.7 μg/mL). Ref: J. C. Coll, et al, JNP, 2002, 65, 753│ H. Greve, et al, JNP, 2008, 71, 309 OH N H N O 9

34

Br

HO

O OH

O

Br 28

Br

O 24

N H N OH

264 Bastadin 22 Type: Halogenated tyrosinoids. C34H24Br6N4O8 Amorph. solid, mp 198–202 °C. Source: Sponge Dendrilla cactos. Pharm: Cytotoxic (Sup-T1, IC50 = 7.15 × 10−9 mol/L). Ref: A. V. Reddy, et al, BoMC, 2006, 14, 4452

2.3 Halogenated Tyrosinoids

95

OH N H N 5

Br

O

6

34

11

O

O

Br OH Br

Br HO

Br 28

16

Br

30

O

20

21 25

N H N

HO

265 Bastadin 24 Type: Halogenated tyrosinoids. C34H26Br6N4O9 Amorph. solid, [α]D23 = −36° (c = 0.88, MeOH). Source: Sponge Ianthella quadrangulata. Pharm: Cytotoxic (36 different hmn cell lines, mean IC50 = 1.8 μg/mL); cytotoxic (five of 36 investigated tumor cell lines with selective activities, CNXF-SF268, IC50 = 0.38 μg/mL; LXFA629L, IC50 = 0.37 μg/mL; MAXF-401NL, IC50 = 0.55 μg/mL; MEXF-276L, IC50 = 0.59 μg/mL; PRXF-22RV1, IC50 = 0.46 μg/mL). Ref: H. Greve, et al, JNP, 2008, 71, 309

5

Br

OH

N

H N O

6

34

11

O

O

Br OH Br

Br HO

Br 28

16

Br

20

30

O 21

25

N H HO

OH N

266 Bastadin 25 Type: Halogenated tyrosinoids. C34H26Br4N4O12S Amorph. solid, [α]D17 = +8.5° (c = 0.1, MeOH). Source: Sponge Ianthella flabelliformis. Pharm: δ-Opioid receptor binding affinity (guinea pig, inhibits binding of opioid peptide [3H]DPDPE, 100 μmol/L, 86%). Ref: A. R. Carroll, et al, JNP, 2010, 73, 1173

96

2 Phenylamine and Phenethylamine Amines

OH

N H N

5

Br

O

6

34

11

O

OH S

O

O O

O

Br OH Br

Br 28

16

30

O

20

21

25

N H

OH N

HO

267 Bastadin 26 Type: Halogenated tyrosinoids. C34H28Br4N4O13S Gum, [α]D25 = +59° (c = 0.01, MeOH). Source: Sponge Ianthella flabelliformis. Pharm: δ-Opioid receptor binding affinity (guinea pig, to displace opioid peptide [3H]DPDPE from δ-opioid receptors in membranes, IC50 = 206 nmol/L, Ki = 100 nmol/L, control Naloxone, Ki = 30 nmol/L, selective). Ref: A. R. Carroll, et al, JNP, 2010, 73, 1173

5

H N

6

Br

OH

N

OH

O

11

34

O

O HO

Br 28 30

16

O O Br S O

Br OH

O

20 21

25

N H HO

OH N

268 Bisaprasin Type: Halogenated tyrosinoids. C44H46Br4N8O12S4 Foam. Source: Sponges Jaspis sp. and Poecillastra sp. (association), sponges Thorectopsamma xana, Aplysinella rhax and Pseudoceratina purpurea. Pharm: Cytotoxic (A549, ED50 = 3.40 μg/mL; SK-OV-3, ED50 = 2.78 μg/mL; SK-MEL-2, ED50 = 2.94 μg/mL; XF498, ED50 = 2.44 μg/mL; HCT15, ED50 = 6.00 μg/mL; control Doxorubicin: A549, ED50 = 0.04 μg/mL; SK-OV-3, ED50 = 0.15 μg/mL; SK-MEL-2, ED50 = 0.003 μg/mL; XF498, ED50 = 0.10 μg/mL; HCT15, ED50 = 0.09 μg/mL); DNA methyltransferase inhibitor; histone deacetylase inhibitor;

2.3 Halogenated Tyrosinoids

97

farnesyl-protein transferase inhibitor; leucine aminopeptidase inhibitor; antimicrobial. Ref: P. B. Shinde, et al, BoMCL, 2008, 18, 6414│ CRC Press, DNP on DVD, 2012, version 20.2 HO

N

N

OH

H N

H N

S

S O

O OH

OH Br

Br Br

Br OH

OH

O

HO

S

N H

N

S

O

N H

N

OH

269 Bispsammaplin A Type: Halogenated tyrosinoids. C44H46Br4N8O12S4 Yellow oil, [α]D23 = −3° (c = 0.21, MeOH). Source: Sponges Jaspis sp. and Poecillastra sp. (association). Pharm: Cytotoxic (A549, ED50 = 1.53 μg/mL; SK-OV-3, ED50 = 1.52 μg/mL; SK-MEL-2, ED50 = 1.02 μg/mL; XF498, ED50 = 1.10 μg/mL; HCT15, ED50 = 3.35 μg/mL; control Doxorubicin: A549, ED50 = 0.04 μg/mL; SK-OV-3, ED50 = 0.15 μg/mL; SK-MEL-2, ED50 = 0.003 μg/mL; XF498, ED50 = 0.10 μg/mL; HCT15, ED50 = 0.09 μg/mL). Ref: Y. Park, et al, JNP, 2003, 66, 1495│ P. B. Shinde, et al, BoMCL, 2008, 18, 6414 HO

N

H N

S

S

OH

Br

OH

Br

OH

O

O

HO

OH

O

O

Br

N

H N

N

Br

O N H

S

S

N H

N

OH

270 Botryllamide D Type: Halogenated tyrosinoids. C19H18BrNO4 Gum. Source: Ascidians Botryllus sp. (Siquijor I., Philippiness) and Botryllus schlosseri (Great Barrier Reef). Pharm: Cytotoxic (HCT116, IC50 = 17 μg/mL, marginal activity, inactive in vivo). Ref: L. A. McDonald, et al, Tetrahedron, 1995, 51, 5237

98

2 Phenylamine and Phenethylamine Amines

OH

O

O N H

Br

O

271 Botryllamide G Type: Halogenated tyrosinoids. C18H15Br2NO4 Gum. Source: Ascidian Botrylloides tyreum. Pharm: ABCG2 inhibitor (ABCG2 is a hmn transporter protein linked to multidrug resistance, most potent and specific). Ref: M. R. Rao, et al, JNP, 2004, 67, 1064│ J. W. Blunt, et al, NPR, 2011, 28, 196 (rev). Br HO O Br

N H O

OH

272 Bromopsammaplin A Type: Halogenated tyrosinoids. C22H23Br3N4O6S2 Amorph. solid. Source: Sponges Jaspis sp. and Poecillastra wondoensis (association). Pharm: Cytotoxic (A549, ED50 = 1.34 μg/mL; SK-OV-3, ED50 = 1.38 μg/mL; SK-MEL-2, ED50 = 0.90 μg/mL; XF498, ED50 = 0.92 μg/mL; HCT15, ED50 = 3.31 μg/mL; control Doxorubicin: A549, ED50 = 0.04 μg/mL; SK-OV-3, ED50 = 0.15 μg/mL; SK-MEL-2, ED50 = 0.003 μg/mL; XF498, ED50 = 0.10 μg/mL; HCT15, ED50 = 0.09 μg/mL). Ref: P. B. Shinde, et al, BoMCL, 2008, 18, 6414 OH

OH

Br

Br

Br 2

6

O

O

1

S

7

N H N HO

12

S N H N OH

273 Ceratinamine Pseudoceramine Type: Halogenated tyrosinoids. C13H15Br2N3O2 Source: Sponge Pseudoceratina purpurea (Japan). Pharm: Antifoulant (cypris larvae of barnacle Balanus amphitrite, EC50 = 5.0 μg/mL); cytotoxic (mus, P388 leukemia cells, IC50 =

2.3 Halogenated Tyrosinoids

99

3.4 μg/mL). Ref: S. Tsukamoto, et al, JOC, 1996, 61, 2936│ R .C. Schoenfeld, et al, Tet. Lett., 1998, 39, 4147 Br

H 2N

O O

CN

N H

Br

274 Cyclobispsammaplin A Type: Halogenated tyrosinoids. C44H44Br4N8O12S4 Amorph. solid. Source: Sponges Jaspis sp. and Poecillastra sp. (association). Pharm: Cytotoxic (A549, ED50 = 1.95 μg/mL; SK-OV-3, ED50 = 1.21 μg/mL; SK-MEL-2, ED50 = 1.14 μg/mL; XF498, ED50 = 2.88 μg/mL; HCT15, ED50 = 3.82 μg/mL; control Doxorubicin: A549, ED50 = 0.01 μg/mL; SK-OV-3, ED50 = 0.01 μg/mL; SK-MEL-2, ED50 = 0.01 μg/mL; XF498, ED50 = 0.03 μg/mL; HCT15, ED50 = 0.03 μg/mL). Ref: P. B. Shinde, et al, BoMCL, 2008, 18, 6414 OH

HO

N

N

12''

12'''

H N

S

H N

S O

O

Br

OH

Br O

OH

Br

O

O

O

Br

2

6 1

S

7

N H HO

12

S

N H

12'

N

N OH

275 16-Debromoaplysamine 4 Type: Halogenated tyrosinoids. C21H24Br3N3O4 Source: Sponge Psammaplysilla purpurea (depth of 8 – 10 m, Mandapam, Tamil Nadu, India). Pharm: Antibacterial (Escherichia coli, MIC = 250 μg/mL; Staphylococcus aureus, MIC = 200 μg/mL; Salmonella typhi, MIC > 50 μg/mL; Vibrio cholera, MIC = 100 μg/mL; control Streptomycin, all MICs = 10 μg/mL). Ref: S. Tilvi, et al, Tetrahedron, 2004, 60, 10207 Br OH

O N

H N

Br

Br O O

NH 2

100

2 Phenylamine and Phenethylamine Amines

276 11-Deoxyfistularin 3 Type: Halogenated tyrosinoids. C31H30Br6N4O10 Powder, mp 128–130 °C, [α]D25 = +194.2° (c = 4.12, MeOH). Source: Sponges Aplysina fistularis, Aplysina insularis (Venezuela) and Aplysina cavernicola (Mediterranean). Pharm: Cytotoxic (MCF7, IC50 = 17 μg/mL; X-17, HeLa, Hep2, RD and LoVo, IC50s > 50 μg/mL). Ref: P. Ciminiello, et al, Tetrahedron, 1997, 53, 6565│ R. S. Compagnone, et al, JNP, 1999, 62, 1443 O O

HO

Br

N

N H

Br

O OH

HO Br

O

Br

H N

N

Br

Br

O

O

11

O

277 Diguanidium salt of psammaplin A sulfate Type: Halogenated tyrosinoids. C32H48Br2N8O10S4 Source: Sponges Jaspis sp. and Poecillastra sp. (association). Pharm: Cytotoxic (A549, ED50 = 12.27 μg/mL, SK-OV-3, ED50 = 1.79 μg/mL, SK-MEL-2, ED50 = 4.48 μg/mL, XF498, ED50 = 16.92 μg/mL, HCT15, ED50 = 43.17 μg/mL, control Doxorubicin: A549, ED50 = 0.01 μg/mL, SKOV-3, ED50 = 0.01 μg/mL, SK-MEL-2, ED50 = 0.01 μg/mL, XF498, ED50 = 0.03 μg/mL, HCT15, ED50 = 0.03 μg/mL). Ref: P. B. Shinde, et al, BoMCL, 2008, 18, 6414 O S

O

O

O

O H 2N

Br

+

C O

+

C

H 2N

N H HO

H 2N N

S

S Br

N

H 2N S

O

O N H OH

278 3- (3,5-Diiodo-4-methoxyphenyl)-3’- (3-iodo-4-methoxyphenyl)N,N′- (1,5-pentanediyl)bis (2-dimethylaminopropanamide) Type: Halogenated tyrosinoids. C29H41I3N4O4 Needles (CHCl3/EtOAc), mp 135–137 °C, [α]D = −0.23° (c. = 0.51, CHCl3). Source: Ascidian Aplidium sp. (Australia). Pharm: Glutathione reductase inhibitor; cytotoxic. Ref: A. R. Carroll, et al, Aust. J. Chem., 1993, 46, 825

2.3 Halogenated Tyrosinoids

H N

H N

O

101

O

N

N

I

I

I O

O

279 15,34-Di-O-sulfatobastadin 7 Type: Halogenated tyrosinoids. C34H26Br4N4O14S2 Yellow solid (di–Na salt). Source: Sponge Ianthella basta. Pharm: Ca2+channel agonist (sarcoplasmic reticulum, EC50 = 13.6 μmol/L). Ref: M. A. Franklin, et al, JNP, 1996, 59, 1121 OH N H N 5 6

Br

O 34

11

OH O

S

O

O

Br

O

O Br S

O 28 30

16

Br

O OH

O

O

20 21

25

N H N HO

280 Hemibastadin 2 Type: Halogenated tyrosinoids. C17H15Br3N2O4 Solid. Source: Sponge Ianthella basta. Pharm: Antibacterial; cytotoxic; anti-inflammatory. Ref: M. S. Butler, et al, Aust. J. Chem., 1991, 44, 287│ H. H. Wassermann, et al, JOC, 1998, 63, 5581 OH

Br Br

Br

OH

O N H N HO

102

2 Phenylamine and Phenethylamine Amines

281 Isofistularin 3 Type: Halogenated tyrosinoids. C31H30Br6N4O11 [α]D = +108° (c = 2.75, MeOH). Source: Sponge Verongia aerophoba. Pharm: Cytotoxic (KB, 4 μg/mL). Ref: G. Cimino, et al, Tet. Lett., 1983, 24, 3029 O Br

Br O Br

OH

Br OH Br

HO O

OH

H N

N

O

H N

N O

O Br

O

282 JBIR 44 Type: Halogenated tyrosinoids. C18H16Br4N2O4 Oil. Source: Sponge Psammaplysilla purpurea (Kinwan Bay, Okinawa). Pharm: Cytotoxic (WST-8 colorimetric assay 48h, HeLa, IC50 = 3.7 μmol/L). Ref: T. Fujiwara, et al, J. Antibiot., 2009, 62, 393 O Br

Br 4

2

OH

Br

N

HO 14

N H

Br

O

283 11-Ketofistularin 3 11-Oxofistularin 3 Type: Halogenated tyrosinoids. C31H28Br6N4O11 Pale yellow gum, [α]D26 = +130° (c = 0.1, MeOH). Source: Sponge Aplysina archeri. Pharm: Antiviral (inhibits growth of feline leukaemia virus, ED50 = 42 μmol/L). Ref: S. P. Gunasekera, et al, JNP, 1992, 55, 509 O

O Br

Br

Br

Br

Br

HO O

H N

N

OH O

11

O

OH

O

O H N

N

17

Br

O

2.3 Halogenated Tyrosinoids

103

284 Neoaplaminone Type: Halogenated tyrosinoids. C26H40BrNO4 Oil, [α]D23 = −5.3° (c = 0.65, MeOH). Source: Sea hare Aplysia kurodai. Pharm: Cytotoxic (HeLa-S3, IC50 = 0.00016 ng/mL). Ref: H. Kigoshi, et al, Tet. Lett., 1990, 31, 4911│ H. Kigoshi, et al, Tet. Lett., 1992, 33, 4195 O Br

OH

N OH

O

285 Neoaplaminone sulfate Type: Halogenated tyrosinoids. C26H40BrNO7S [α]D27 = −3° (c = 1.29, MeOH). Source: Sea hare Aplysia kurodai. Pharm: Cytotoxic. Ref: H. Kigoshi, et al, Tet. Lett., 1990, 31, 4911; 1992, 33, 4195 O Br

O

O S

3

O

OH

N OH

9' 11'

O

286 N,N′- (1,5-Pentanediyl)bis[3-(3,5-diiodo-4-methoxyphenyl)2-dimethylamino-propanamide] Type: Halogenated tyrosinoids. C29H40I4N4O4 Needles (CHCl3/EtOAc), mp 114–116 °C, [α]D = −0.20° (c = 0.35, CHCl3). Source: Ascidian Aplidium sp. (Australia). Pharm: Glutathione reductase inhibitor; cytotoxic. Ref: A. R. Carroll, et al, Aust. J. Chem., 1993, 46, 825 O

H N

H N

O

N

N

I

I O

I

I O

104

2 Phenylamine and Phenethylamine Amines

287 Psammaplin A Type: Halogenated tyrosinoids. C22H24Br2N4O6S2 Semicryst. solid, mp 67–75 °C. Source: Sponges Jaspis sp. and Poecillastra sp. (association), sponges Aplysinella rhax, Pseudoceratina purpurea and Thorectopsamma xana. Pharm: Cytotoxic (A549, ED50 = 0.57 μg/mL; SK-OV-3, ED50 = 0.14 μg/mL; SK-MEL-2, ED50 = 0.13 μg/mL; XF498, ED50 = 0.57 μg/mL; HCT15, ED50 = 0.68 μg/mL; control Doxorubicin: A549, ED50 = 0.04 μg/mL; SK-OV-3, ED50 = 0.15 μg/mL; SK-MEL-2, ED50 = 0.003 μg/mL; XF498, ED50 = 0.10 μg/mL; HCT15, ED50 = 0.09 μg/mL); inhibitors of chitinase, histone deacetylase and DNA methyltransferase; antifungal; inhibitors of farnesyl protein transferase and leucine aminopeptidase; antimicrobial. Ref: L. Arabshahi, et al, JOC, 1987, 52, 3584│ A. D. Rodriguez, et al, Tet. Lett., 1987, 28, 4989│ C. Jimenez, et al, Tetrahedron, 1991, 47, 2097│ Y. Park, et al, JNP, 2003, 66, 1495│ I. C. Piña, JOC, 2003, 68, 3866│ F. D. Mora, et al, JNP, 2006, 69, 547│ P. B. Shinde, et al, BoMCL, 2008, 18, 6414│ S. K. Graham, et al, Aust. J. Chem., 2010, 63, 867 HO

N

H N

S

N

H N

S

OH

O

O 5'

5''

Br

Br OH

OH

288 Psammaplin B Type: Halogenated tyrosinoids. C12H12BrN3O3S Oil. Source: Sponges Jaspis sp. and Poecillastra sp. (association), sponge Pseudoceratina purpurea. Pharm: Cytotoxic (A549, ED50 = 12.84 μg/mL; SK-OV-3, ED50 = 9.27 μg/mL; SK-MEL-2, ED50 = 19.43 μg/mL; XF498, ED50 = 10.92 μg/mL; HCT15, ED50 > 30 μg/mL; control Doxorubicin: A549, ED50 = 0.02 μg/mL; SK-OV-3, ED50 = 0.07 μg/mL; SK-MEL-2, ED50 = 0.10 μg/mL; XF498, ED50 = 0.10 μg/mL; HCT15, ED50 = 0.33 μg/mL). Ref: C. Jimenez, et al, Tetrahedron, 1991, 47, 2097│ I. C. Piña, JOC, 2003, 68, 3866│ P. B. Shinde, et al, BoMCL, 2008, 18, 6414 HO

N

N

H N S O

Br OH

2.3 Halogenated Tyrosinoids

105

289 Psammaplin D Type: Halogenated tyrosinoids. C15H20BrN3O5S2 Oil. Source: Sponges Jaspis sp. and Poecillastra sp. (association), sponge Pseudoceratina purpurea. Pharm: Cytotoxic (A549, ED50 = 0.80 μg/mL; SK-OV-3, ED50 = 0.17 μg/mL; SK-MEL-2, ED50 = 0.20 μg/mL; XF498, ED50 = 0.60 μg/mL; HCT15, ED50 = 1.23 μg/mL; control Doxorubicin: A549, ED50 = 0.04 μg/mL; SK-OV-3, ED50 = 0.15 μg/mL; SK-MEL-2, ED50 = 0.003 μg/mL; XF498, ED50 = 0.10 μg/mL; HCT15, ED50 = 0.09 μg/mL); antimicrobial; tyrosine kinase inhibitor (mild). Ref: C. Jimenez, et al, Tetrahedron, 1991, 47, 2097│ Y. Park, et al, JNP, 2003, 66, 1495│ I. C. Piña, JOC, 2003, 68, 3866│ P. B. Shinde, et al, BoMCL, 2008, 18, 6414 O

H N

S

Br

O

N HO

O

S

N H HO

290 Psammaplin E Type: Halogenated tyrosinoids. C15H19BrN4O5S2 Source: Sponges Jaspis sp. and Poecillastra sp. (association), sponge Pseudoceratina purpurea. Pharm: Cytotoxic (A549, ED50 = 1.47 μg/mL; SK-OV-3, ED50 = 0.19 μg/mL; SK-MEL-2, ED50 = 0.21 μg/mL; XF498, ED50 = 1.63 μg/mL; HCT15, ED50 = 1.92 μg/mL; control Doxorubicin: A549, ED50 = 0.01 μg/mL; SK-OV-3, ED50 = 0.01 μg/mL; SK-MEL-2, ED50 = 0.01 μg/mL; XF498, ED50 = 0.03 μg/mL; HCT15, ED50 = 0.03 μg/mL). Ref: P. B. Shinde, et al, BoMCL, 2008, 18, 6414│ I. C. Piña, et al, JOC, 2003, 68, 3866 O

O Br

HO

HO

N H

N

S

S

H N

NH2 O

291 Psammaplin F Type: Halogenated tyrosinoids. C15H18BrN3O6S2 Source: Sponge Pseudoceratina purpurea. Pharm: Histone deacetylase inhibitor (potent). Ref: I. C. Piña, JOC, 2003, 68, 3866 O

O S

Br

N H N

HO

S

H N

OH O

HO

292 Psammaplin G Type: Halogenated tyrosinoids. C15H20BrN5O5S2 Source: Sponge Pseudoceratina purpurea. Pharm: DNA methyltransferase inhibitor (potent). Ref: I. C. Pina, et al, JOC, 2003, 68, 3866

106

2 Phenylamine and Phenethylamine Amines

NH2

O S

Br

H N

N

O

OH

S

N H N HO

HO

293 Psammaplin I Type: Halogenated tyrosinoids. C12H15BrN2O5S Amorph. solid, [α]D = +32.7° (c = 0.03, MeOH). Source: Sponges Jaspis sp. and Poecillastra sp. (association), sponges Aplysinella rhax and Pseudoceratina purpurea. Pharm: Cytotoxic (A549, ED50 = 4.15 μg/mL; SK-OV-3, ED50 = 1.76 μg/mL; SK-MEL-2, ED50 = 2.84 μg/mL; XF498, ED50 = 2.96 μg/mL; HCT15, ED50 = 6.51 μg/mL; control Doxorubicin: A549, ED50 = 0.02 μg/mL; SK-OV-3, ED50 = 0.07 μg/mL; SK-MEL-2, ED50 = 0.10 μg/mL; XF498, ED50 = 0.10 μg/mL; HCT15, ED50 = 0.33 μg/mL). Ref: P. B. Shinde, et al, BoMCL, 2008, 18, 641│ I. C. Piña, et al, JOC, 2003, 68, 3866│ S. K. Graham, et al, Aust. J. Chem., 2010, 63, 867 O

O

S

Br

HO

HO

N H

N

O

294 Psammaplysene A Type: Halogenated tyrosinoids. C27H35Br4N3O3 Source: Sponge Psammaplysilla sp. Pharm: FOXO1a nuclear export inhibitor (FOXO1a is a downstream target of the PTEN tumor suppressor, Psammaplysene A compensates for PTEN loss by relocalizing the transcription factor FOXO1a to the nucleus). Ref: F. C. Schroeder, et al, JNP, 2005, 68, 574 Br H N

O

O

15

Br

N

7

Br

Br O

N 1

295 Psammaplysene B Type: Halogenated tyrosinoids. C26H33Br4N3O3 Source: Sponge Psammoclemma sp. Pharm: FOXO1a nuclear export inhibitor (specific). Ref: F. C. Schroeder, et al, JNP, 2005, 68, 574

2.3 Halogenated Tyrosinoids

107

Br H N

O

O

15

Br

N

7

Br

Br H N

O

1

296 Psammaplysene C Type: Halogenated tyrosinoids. C28H38Br3N3O3 Amorph. solid. Source: Sponge Psammoclemma sp. Pharm: Cytotoxic (biological activity of extract of Psammoclemma sp. is due to cytotoxic psammaplysenes C and D, and not P2X7-specific activity). Ref: M. S. Buchanan, et al, JNP, 2007, 70, 1827 Br O

N

O

15

Br

N

7

Br O

N 1

297 Psammaplysene D Type: Halogenated tyrosinoids. C28H37Br4N3O3 Amorph. solid. Source: Sponge Psammoclemma sp. Pharm: Cytotoxic (biological activity of extract of Psammoclemma sp.is due to cytotoxic psammaplysenes C and D, and not P2X7-specific activity). Ref: M. S. Buchanan, et al, JNP, 2007, 70, 1827 Br O

N

O

15

Br

N

7

Br

Br O

N 1

298 Pseudoceratin A Type: Halogenated tyrosinoids. C35H36Br4N6O14 Amorph. solid, [α]D28 = +11.7° (c = 0.1, MeOH). Source: Sponge Pseudoceratina purpurea. Pharm: Antifungal (Candida albicans

108

2 Phenylamine and Phenethylamine Amines

and mutant Saccharomyces cerevisiae, MID = 6.5–8.0 μg). Ref: J. H. Jang, et al, JOC, 2007, 72, 1211 Br

N

H N

OH

O HO

HO

OH

O

O

N

O Br HO

OH

HN

O

21

OH

H N

N

O

O Br

Br

299 Pseudoceratin B Type: Halogenated tyrosinoids. C35H36Br4N6O14 Amorph. solid, [α]D28 = −11.6° (c = 0.1, MeOH). Source: Sponge Pseudoceratina purpurea. Pharm: Antifungal (Candida albicans and mutant Saccharomyces cerevisiae, MID = 6.5–8.0 μg). Ref: J. H. Jang, et al, JOC, 2007, 72, 1211 Br

HO

N

H N

OH

O HO

OH

O

O N

O Br HO

OH

HN

O

H N

N

21

OH

O

O Br

Br

300 Purealidin C Type: Halogenated tyrosinoids. C23H28Br4N4O4 Amorph. Source: Sponge Psammaplysilla purea. Pharm: Cytotoxic (KB, IC50 = 3.2 μg/mL; L1210, IC50 = 2.4 μg/mL); antifungal (Candida albicans, Cryptococcus neoformans and Paecilomyces variotii); antibacterial (Staphylococcus aureus, Sarcina lutea and Bacillus subtilis). Ref: J. Kobayashi, et al, Tetrahedron, 1991, 47, 6617 Br H2N

O

N

OH H N

Br

Br

O

O Br

NH2

2.3 Halogenated Tyrosinoids

109

301 Purealidin F Type: Halogenated tyrosinoids. C14H22Br2N2O Oil. Source: Sponge Psammaplysilla purea (Okinawa). Pharm: Na/K-ATPase inhibitor. Ref: M. Tsuda, et al, Tet. Lett., 1992, 33, 2597│ M. Tsuda, et al, JNP, 1992, 55, 1325│ Y. Venkateswarlu, et al, JNP, 1998, 61, 1388; 1999, 62, 893 N

Br Br

H N

O

302 Purpuramine C Type: Halogenated tyrosinoids. C25H26Br2N3O31+ Source: Sponge Psammaplysilla purpurea (Japan). Pharm: Antibacterial (Staphylococcus aureus). Ref: H. Yagi, et al, Tetrahedron, 1993, 49, 3749

HO

N H

N

N

Br

O

+

O Br

303 Purpuramine D Type: Halogenated tyrosinoids. C20H23Br2N3O3 Source: Sponge Psammaplysilla purpurea (Japan). Pharm: Antibacterial (Staphylococcus aureus). Ref: H. Yagi, et al, Tetrahedron, 1993, 49, 3749 Br O

O

HO

N

N H

NH2

Br

304 Purpuramine E Type: Halogenated tyrosinoids. C21H25Br2N3O3 Source: Sponge Psammaplysilla purpurea (Japan). Pharm: Antibacterial (Staphylococcus aureus). Ref: S. C. Pakrashi, et al, Tetrahedron, 1990, 50, 12009; 12783│ H. Yagi, et al, Tetrahedron, 1993, 49, 3749

110

2 Phenylamine and Phenethylamine Amines

Br

HO

N

H N

O

O

Br

N H

305 Purpuramine F Type: Halogenated tyrosinoids. C20H22Br3N3O4 Source: Sponge Psammaplysilla purpurea (Japan). Pharm: Antibacterial (Staphylococcus aureus). Ref: S. C. Pakrashi, et al, Tetrahedron, 1990, 50, 12009; 12783│ H. Yagi, et al, Tetrahedron, 1993, 49, 3749 Br O

O Br HO

HO

Br

N H

N

NH2

306 Purpuramine G Type: Halogenated tyrosinoids. C21H24Br3N3O4 Source: Sponge Psammaplysilla purpurea (Japan). Pharm: Antibacterial (Staphylococcus aureus). Ref: S. C. Pakrashi, et al, Tetrahedron, 1990, 50, 12009; 12783│ H. Yagi, et al, Tetrahedron, 1993, 49, 3749 Br O

H N

O Br

HO

HO

N

N H

Br

307 Purpuramine I Type: Halogenated tyrosinoids. C22H26Br3N3O4 Source: Sponges Psammaplysilla purpurea (depth of 8–10 m, Mandapam, Tamil Nadu, India), Psammaplysilla purpurea (Japan), Suberea sp. (Okinawa) and Druinella sp. (Fiji). Pharm: Antibacterial (Escherichia coli, MIC = 100 μg/mL; Staphylococcus aureus, MIC = 50 μg/mL; Vibrio cholera, MIC = 100 μg/mL; control Streptomycin, all MICs = 10 μg/mL); cytotoxic (ovarian tumor A2780, IC50 = 1.70 μg/mL; leukaemia K562, IC50 = 1.24 μg/mL); antibacterial (Staphylococcus aureus). Ref: H. Yagi, et al, Tetrahedron, 1989, 49, 3749│ S. C. Pakrashi, et al, Tetrahedron, 1990, 50, 12009; 12783│ J. N. M. Tsuda, et al, JNP, 2001, 64, 980│ S. Tilvi, et al, Tetrahedron, 2004, 60, 10207

2.3 Halogenated Tyrosinoids

111

O Br

4 2

Br

N

O

HN

OH

14

20

O

N H

Br

308 Purpuramine J Type: Halogenated tyrosinoids. C23H28Br3N3O5 Colorless oil. Source: Sponge Druinella sp. (yield = 0.0030%, Fiji). Pharm: Cytotoxic (A2780, IC50 = 6.77 μg/mL; K562, IC50 = 5.97 μg/mL). Ref: J. N. Tabudravu, et al, JNP, 2002, 65, 1798│ H. Yagi, et al, Tetrahedron, 1989, 49, 3749 O Br

4 2

Br O

OH N

O

N

14

20

Br

O

N H

309 Purpurealidin B Type: Halogenated tyrosinoids. C22H24Br3N3O4 Amorph. solid, mp 175.8 °C. Source: Sponge Psammaplysilla purpurea (depth of 8–10 m, Mandapam, Tamil Nadu, India). Pharm: Antibacterial (Escherichia coli, MIC > 12 μg/mL; Staphylococcus aureus, MIC = 10 μg/mL; Shigella flexneri, MIC = 100 μg/mL; Vibrio cholera, MIC = 25 μg/mL; control Streptomycin, all MICs = 10 μg/mL). Ref: S. Tilvi, et al, Tetrahedron, 2004, 60, 10207 O Br Br O

H N

N O

N O

Br

112

2 Phenylamine and Phenethylamine Amines

310 Sesquibastadin Type: Halogenated tyrosinoids. C51H44Br6N6O12 Source: Sponge Ianthella basta (Ambon, Indonesia). Pharm: protein kinases inhibitor (variety of a panel of 24 enzymes). Ref: H. Niemann, et al, JNP, 2013, 76, 121 O Br

N H N

Br OH

N

H N

OH

OH

OH

OH

Br Br

O

OH Br

O HO

HO

N

H N

Br O

311 Sodium Salt of Psammaplin A Sulfate Type: Halogenated tyrosinoids. C22H23Br2N4O9S31- Source: Sponges Jaspis sp. and Poecillastra sp. (association). Pharm: Cytotoxic (A549, ED50 = 0.18 μg/mL; SK-OV-3, ED50 = 0.16 μg/mL; SK-MEL-2, ED50 = 1.13 μg/mL; XF498, ED50 = 0.18 μg/mL; HCT15, ED50 = 1.25 μg/mL; control Doxorubicin: A549, ED50 = 0.02 μg/mL; SK-OV-3, ED50 = 0.07 μg/mL; SK-MEL-2, ED50 = 0.10 μg/mL; XF498, ED50 = 0.10 μg/mL; HCT15, ED50 = 0.33 μg/mL). Ref: P. B. Shinde, et al, BoMCL, 2008, 18, 6414 O O O

OH

S

O Br

Br 2

6

O

O

1

S

7

N H HO

N

12

S

N H

N

OH

312 Suberedamine A Type: Halogenated tyrosinoids. C23H30Br3N3O3 Amorph. solid, mp 64–67 °C, [α]D25 = +21° (c = 1, MeOH). Source: Sponge Suberea sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 8.0 μg/mL; KB, IC50 = 9.0 μg/mL); antibacterial (Micrococcus luteus, MIC = 12.6 μg/mL). Ref: M. Tsuda, et al, JNP, 2001, 64, 980

2.3 Halogenated Tyrosinoids

113

O NH2 Br

H N

Br

S

O

O

N

Br

313 Suberedamine B Type: Halogenated tyrosinoids. C24H32Br3N3O3 Amorph. solid, mp 79–81 °C, [α]D25 = + 16°(c = 1, MeOH). Source: Sponge Suberea sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 8.6 μg/mL; KB, IC50 > 10 μg/mL); antibacterial (Micrococcus luteus, MIC = 12.6 μg/mL). Ref: M. Tsuda, et al, JNP, 2001, 64, 980 O

HN H N

Br

Br

S

O

O

N

Br

314 10-O-Sulfatobastadin 3 Type: Halogenated tyrosinoids. C34H30Br4N4O11S Powder (Na salt). Source: Sponge Ianthella basta. Pharm: Ca2+ channel agonist (sarcoplasmic reticulum, EC50 = 100 μmol/L). Ref: M. A. Franklin, et al, JNP, 1996, 59, 1121

HO O

O S

Br

O

N

H N

OH

10

HO

OH

O

Br Br OH

O

Br N H

N

OH

315 34-Sulfobastadin 13 Type: Halogenated tyrosinoids. C34H28Br4N4O11S Source: Sponge Ianthella sp. (Great Barrier Reef, Australia). Pharm: Endothelin A receptor inhibitor; ATP citrate lyase inhibitor. Ref: N. K. Gulavita, et al, JNP, 1993, 56, 1613

114

2 Phenylamine and Phenethylamine Amines

N

H N

OH

O Br

HO O

H

O

O O S O O Br

Br

Br

O N H

N

OH

316 1-O-Sulfohemibastadin 1 4-O-Sulfohemibastadin 1 Type: Halogenated tyrosinoids. C17H16Br2N2O7S Colorless solid. Source: Sponge Ianthella basta (Guam). Pharm: Antagonist of RyR1-FKBP12 Ca2+ channel (ryanodine binding, IC50 = 13 μmolL, opposite effect of Bastadin 5). Ref: M. N. Masuno, et al, Mar. Drugs, 2004, 2, 176 OH N

HO O

O S

Br

H N O

O Br OH

317 1-O-Sulfohemibastadin 2 4-O-Sulfohemibastadin 2 Type: Halogenated tyrosinoids. C17H15Br3N2O7S Colorless solid. Source: Sponge Ianthella basta (Guam). Pharm: Antagonist of RyR1-FKBP12 Ca2+ channel (ryanodine binding, IC50 = 29 μmolL, opposite effect of Bastadin 5). Ref: M. N. Masuno, et al, Mar. Drugs, 2004, 2, 176

HO O

O S

Br

O

N

H N

OH

O

Br

Br OH

2.3 Halogenated Tyrosinoids

115

318 15-O-Sulfonatobastadin 11 Type: Halogenated tyrosinoids. C34H26Br4N4O11S Amorph. solid. Source: Sponge Ianthella flabelliformis. Pharm: δ-Opioid receptor binding affinity (guinea pig, inhibits binding of opioid peptide [3H]DPDPE, 100 μmol/L, 87%). Ref: A. R. Carroll, et al, JNP, 2010, 73, 1173

5

Br

OH

N

H N O

6

34

11

O

OH O O S

O

O

Br OH Br

Br 28

16 20

30

O 21 25

N H HO

N

319 Tokaradine A Type: Halogenated tyrosinoids. C28H31Br4N4O41+ Amorph. yellow solid. Source: Sponge Pseudoceratina purpurea (Southern Japan). Pharm: Toxic (crab Hemigrapsus sanguineus). Ref: N. Fusetani, et al, Tetrahedron, 2001, 57, 7507 Br O NH2

N

OH H N

Br

Br

O

N

+

O Br

320 Tokaradine B Type: Halogenated tyrosinoids. C28H31Br4N4O41+ Amorph. yellow solid. Source: Sponge Pseudoceratina purpurea (Southern Japan). Pharm: Toxic (crab Hemigrapsus sanguineus). Ref: N. Fusetani, et al, Tetrahedron, 2001, 57, 7507

116

2 Phenylamine and Phenethylamine Amines

Br O N

N

OH

NH2

H N

+

Br

Br

O

O Br

2.4 Miscellaneous Phenethylamines 321 Ceratinine A Type: Miscellaneous phenethylamines. C12H18Br2N2O2 Yellow oil, [α]D25 = −22° (c = 0.47, MeOH). Source: Sponge Pseudoceratina arabica (Hurghada, Egypt). Pharm: Antimigratory activity (wound healing assay, highly metastatic MDAMB-231 hmn breast cancer cells, 10 μmol/L, migration ≈ 68%, 30 μmol/L, migration ≈ 72%, control 4-S-Ethylphenylmethylene hydantoin, 30 μmol/L, migration ≈ 38%, negative control DMSO, migration = 100%); anti-invasive activity (Cultrex BME (basement membrane extract) cell invasion assay, highly metastatic MDA-MB-231 hmn breast cancer cells, 10 μmol/L, invasion ≈ 119%, control 4-S-Ethylphenylmethylene hydantoin, 50 μmol/L, invasion ≈ 53%, negative control DMSO, invasion = 100%). Ref: L. A. Shaala, et al, Mar. Drugs, 2012, 10, 2492 Br O

H 2N

NH2

Br O

322 Ceratinine B Type: Miscellaneous phenethylamines. C13H16Br2N2O2 Off-white amorph. powder, [α]D25 = −16° (c = 0.25, MeOH). Source: Sponge Pseudoceratina arabica (Hurghada, Egypt). Pharm: Antimigratory activity (wound healing assay, highly metastatic MDAMB-231 hmn breast cancer cells, 10 μmol/L, migration ≈ 80%, 30 μmol/L, migration ≈ 88%, control 4-S-Ethylphenylmethylene hydantoin, 30 μmol/L, migration ≈ 38%, negative control DMSO, migration = 100%); anti-invasive activity (Cultrex BME (basement membrane extract) cell invasion assay, highly metastatic MDA-MB-231 hmn breast cancer cells, 10 μmol/L, invasion ≈ 73%, control 4-S-Ethylphenylmethylene hydantoin, 50 μmol/L, invasion ≈ 53%, negative control DMSO, invasion = 100%). Ref: L. A. Shaala, et al, Mar. Drugs, 2012, 10, 2492

2.4 Miscellaneous Phenethylamines

117

Br O O NH2

Br NH

323 Ceratinine D Type: Miscellaneous phenethylamines. C14H17Br2N3O4 Off-white amorph. powder. Source: Sponge Pseudoceratina arabica (Hurghada, Egypt). Pharm: Antimigratory activity (wound healing assay, highly metastatic MDA-MB-231 hmn breast cancer cells, 10 μmol/L, migration ≈ 77%, 30 μmol/L, migration ≈ 70%, control 4-S-Ethylphenylmethylene hydantoin, 30 μmol/L, migration ≈ 38%, negative control DMSO, migration = 100%); anti-invasive activity (Cultrex BME (basement membrane extract) cell invasion assay, highly metastatic MDA-MB-231 hmn breast cancer cells, 10 μmol/L, invasion ≈ 68%, control 4-S-Ethylphenylmethylene hydantoin, 50 μmol/L, invasion ≈ 53%, negative control DMSO, invasion = 100%). Ref: L. A. Shaala, et al, Mar. Drugs, 2012, 10, 2492 O

Br O

O

H N

NH2 O

H

N H

Br

324 Convolutamine D Type: Miscellaneous phenethylamines. C13H16Br3NO2 Oil. Source: Bryozoan Amathia convoluta (Florida). Pharm: Cytotoxic (P388, L1210, KB). Ref: H. Zhang, et al, Chem. Lett., 1994, 2271│ H. Zhang, et al, Tetrahedron, 1994, 50, 10201 O Br

Br

N Br

O

325 Convolutamine E Type: Miscellaneous phenethylamines. C15H20Br3NO3 Oil. Source: Bryozoan Amathia convoluta (Florida). Pharm: Cytotoxic (P388, L1210, KB). Ref: H. Zhang, et al, Chem. Lett., 1994, 2271│ H. Zhang, et al, Tetrahedron, 1994, 50, 10201

118

2 Phenylamine and Phenethylamine Amines

O Br

Br

N O

Br HO

326 Hydroxymoloka’iamine Type: Miscellaneous phenethylamines. C11H16Br2N2O2 Source: Sponge Pseudoceratina arabica (Hurghada, Egypt). Pharm: Antimigratory activity (wound healing assay, highly metastatic MDA-MB-231 hmn breast cancer cells, 10 μmol/L, migration ≈ 100%, 30 μmol/L, migration ≈ 78%, control 4-S-Ethylphenylmethylene hydantoin, 30 μmol/L, migration ≈ 38%, negative control DMSO, migration = 100%). Ref: L. A. Shaala, et al, Mar. Drugs, 2012, 10, 2492 Br O

H 2N

NH2

Br OH

327 Ianthellamide A Type: Miscellaneous phenethylamines. C13H18Br2N2O6S Source: Sponge Ianthella quadrangulata (Harrier Point, Orpheus Is., Queensland). Pharm: Kynurenine-3-hydroxylase inhibitor (modest, potent and selective). Ref: Y. Feng, et al, BoMCL, 2012, 22, 3398 O H 2N

HN Br

Br O HO

O

O

S O

328 Molokaiakitamide Type: Miscellaneous phenethylamines. C13H17Br2N3O3 Source: Sponge Pseudoceratina arabica (Hurghada, Egypt). Pharm: Antimigratory activity (wound healing assay, highly metastatic MDA-MB-231 hmn breast cancer cells, 10 μmol/L, migration ≈ 86%, 30 μmol/L, migration ≈ 66%, control 4-SEthylphenylmethylene hydantoin, 30 μmol/L, migration ≈ 38%, negative control

2.4 Miscellaneous Phenethylamines

119

DMSO, migration = 100%); anti-invasive activity (Cultrex BME (basement membrane extract) cell invasion assay, highly metastatic MDA-MB-231 hmn breast cancer cells, 10 μmol/L, invasion ≈ 110%, control 4-S-Ethylphenylmethylene hydantoin, 50 μmol/L, invasion ≈ 53%, negative control DMSO, invasion = 100%). Ref: L. A. Shaala, et al, Mar. Drugs, 2012, 10, 2492 O

Br

H N

O

NH2 O

H 2N

Br

329 Molokaiamine Type: Miscellaneous phenethylamines. C11H16Br2N2O Off-white powder (MeOH) (dihydrochloride). Source: Sponges Pseudoceratina arabica (Hurghada, Egypt), Pseudoceratina purpurea, Psammaplysilla sp. and Aplysinella sp. Pharm: Antimigratory activity (wound healing assay, highly metastatic MDA-MB-231 hmn breast cancer cells, 10 μmol/L, migration ≈ 54%, 30 μmol/L, migration ≈ 53%, control 4-SEthylphenylmethylene hydantoin, 30 μmol/L, migration ≈ 38%, negative control DMSO, migration = 100%); anti-invasive activity (Cultrex BME (basement membrane extract) cell invasion assay, highly metastatic MDA-MB-231 hmn breast cancer cells, 10 μmol/L, invasion ≈ 103%, control 4-S-Ethylphenylmethylene hydantoin, 50 μmol/L, invasion ≈ 53%, negative control DMSO, invasion = 100%). Ref: L. A. Shaala, et al, Mar. Drugs, 2012, 10, 2492│ Y. Venkateswarlu, et al, JNP, 1998, 61, 1388; 1999, 62, 893 Br NH2

O

H 2N

Br

330 Purpuramine A Type: Miscellaneous phenethylamines. C20H23Br2N3O3 Source: Sponge Psammaplysilla purpurea (Japan). Pharm: Antibacterial (Staphylococcus aureus). Ref: H. Yagi, et al, Tetrahedron, 1993, 49, 3749

HO

N

NH2

Br

O N H

O Br

331 Purpuramine B Type: Miscellaneous phenethylamines. C20H24BrN3O3 Source: Sponge Psammaplysilla purpurea (Japan). Pharm: Antibacterial (Staphylococcus aureus). Ref: H. Yagi, et al, Tetrahedron, 1993, 49, 3749

120

2 Phenylamine and Phenethylamine Amines

HO

O

N H

N

NH2

Br

O

332 Shishididemniol A Type: Miscellaneous phenethylamines. C45H81N3O11 Oil, [α]D20 = −33.7° (c = 1, MeOH). Source: An unidentified ascidian (family Didemnidae, yield = 0.051% ww). Pharm: Antibacterial (disk agar diffusion assay, fish pathogen Vibrio anguillarum (20 μg/6.5 mm disk, IZD = 8 mm)). Ref: H. Kobayashi, et al, JOC, 2007, 72, 1218 O HN HO 10'

O

O

O

2' 7

N H OH

OH

8

OH OH

O

HO

NH2

333 Shishididemniol B Type: Miscellaneous phenethylamines. C45H82ClN3O11 Oil, [α]D20 = −19.4° (c = 1, MeOH). Source: An unidentified ascidian (family Didemnidae, yield = 0.019% ww). Pharm: Antibacterial (disk agar diffusion assay, fish pathogen Vibrio anguillarum (20 μg/6.5 mm disk, IZD = 7 mm)). Ref: H. Kobayashi, et al, JOC, 2007, 72, 1218 O HN HO 10'

O O

HO

Cl

2' 7

N H OH

OH

8

OH OH

HO

O NH2

2.4 Miscellaneous Phenethylamines

121

334 Xanthocillin X Type: Miscellaneous phenethylamines. C18H12N2O2 Source: Deep-sea fungus Penicillium commune SD-118 (sediment). Pharm: Antibacterial (100 μg/disk: Staphylococcus aureus, IZD = 18 mm; Escherichia coli, IZD = 17 mm); antibacterial (Staphylococcus aureus, MIC = 2 μg/mL; Escherichia coli, MIC = 1 μg/mL); antifungal (Alternaria brassicae, MIC = 32 μg/mL); cytotoxic (MCF7, IC50 = 12.0 μg/mL; SW1990, IC50 = 12 μg/ mL; HepG2, IC50 = 7.0 μg/mL; H460, IC50 = 10.0 μg/mL; A549, IC50 = 10 μg/mL; HeLa, IC50 = 10.0 μg/mL; DU145, IC50 = 8.0 μg/mL; MDA-MB-231, IC50 = 8.0 μg/mL). Ref: Z. Shang, et al, Chin. J. Oceanol. Limnol. 2012, 30, 305│ Y. Zhao, et al, Mar. Drugs, 2012, 10, 1345 C N

N HO

C

+

+

OH

3 Pyrrole Indole and Imidazole Alkaloids 3.1 Pyrrole Alkaloids 335 Agelanesin A Type: Simple pyrrole alkaloids. C18H23Br2N3O2 Source: Sponge Agelas linnaei. Pharm: Cytotoxic (L5178Y, IC50 = 9.55 μmol/L); antibacterial (Staphylococcus epidermidis, MIC > 42 μmol/L). Ref: T. Hertiani, et al, BoMC, 2010, 18, 1297 O H N

O

N H

Br

Br N

336 Agelanesin B Type: Simple pyrrole alkaloids. C18H23BrIN3O2 Source: Sponge Agelas linnaei. Pharm: Cytotoxic (L5178Y, IC50 = 9.25 μmol/L); antibacterial (Staphylococcus epidermidis, MIC > 38 μmol/L). Ref: T. Hertiani, et al, BoMC, 2010, 18, 1297 O H N

N H

O I

Br

N

337 Agelanesin C Type: Simple pyrrole alkaloids. C18H22Br3N3O2 Source: Sponge Agelas linnaei. Pharm: Cytotoxic (L5178Y, IC50 = 16.76 μmol/L); antibacterial (Staphylococcus epidermidis, MIC > 32 μmol/L). Ref: T. Hertiani, et al, BoMC, 2010, 18, 1297 O H N Br

N H

O Br

Br N

https://doi.org/10.1515/9783110655193-003

124

3 Pyrrole Indole and Imidazole Alkaloids

338 Agelanesin D Type: Simple pyrrole alkaloids. C18H22Br2IN3O2 Source: Sponge Agelas linnaei. Pharm: Cytotoxic (L5178Y, IC50 = 13.06 μmol/L); antibacterial (Staphylococcus epidermidis, MIC > 33 μmol/L). Ref: T. Hertiani, et al, BoMC, 2010, 18, 1297 O H N

N H

Br

O I

Br N

339 3-Bromo-1H-pyrrole-2,5-dione Type: Simple pyrrole alkaloids. C4H2BrNO2 Source: Sponge Axinella brevistyla (Japan waters). Pharm: Antifungal (inhibits growth of erg6 mutant of yeast Saccharomyces cerevisiae, < 1.0 μg/disk); cytotoxic (L1210, IC50 = 1.1 μg/mL). Ref: S. Tsukamoto, et al, JNP, 2001, 64, 1576 H

O

Br

O

N H

340 5-(19-Cyanononadecyl)-1H-pyrrole-2-carboxaldehyde Type: Simple pyrrole alkaloids. C25H42N2O Source: Sponges Mycale microsigmatosa (Caribbean Sea), Desmapsamma anchorata (Venezuela) and Mycale cecilia. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration); antileishmanial. Ref: R. S. Compagnone, et al, Nat. Prod. Lett., 1999, 13, 203│ S. -C. Mao, et al, JNP, 2009, 72, 1927 O

H N

H

N

341 Damipipecoline Type: Simple pyrrole alkaloids. C11H13BrN2O4 [α]D20 = +5.4° (c = 0.001, H2O). Source: Sponge Axinella damicornis (Mediterranean Sea). Pharm: Nervous system activity (serotonin receptor modulator, inhibits of serotonin receptor binding, IC50

3.1 Pyrrole Alkaloids

125

(apparent) = 1 μg/mL, MMOA: Ca2+ influx inhibition). Ref: A. Aiello, et al, BoMC 2007, 15, 5877 NH

Br

O O OH NH

O

342 Damituricine Type: Simple pyrrole alkaloids. C12H15BrN2O4 [α]D20 = +10.7° (c = 0.001, H2O). Source: Sponge Axinella damicornis (Mediterranean Sea). Pharm: Nervous system activity (serotonin receptor modulator, inhibits of serotonin receptor binding, IC50 (apparent) = 1 μg/mL, MMOA: Ca2+ influx inhibition). Ref: A. Aiello, et al, BoMC 2007, 15, 5877 NH Br O H O

O

+

N

–

O

343 3,4-Dibromomaleimide 3,4-Dibromo-1H-pyrrole-2,5-dione Type: Simple pyrrole alkaloids. C4HBr2NO2 Yellow needles (xylene or CHCl3), mp 230 °C, mp 226 °C. Source: Sponge Axinella brevistyla (Japan waters). Pharm: Antifungal (inhibits growth of erg6 mutant of yeast Saccharomyces cerevisiae, < 1.0 μg/disk); cytotoxic (L1210, IC50 = 0.66 μg/mL). Ref: S. Tsukamoto, et al, JNP, 2001, 64, 1576 Br

O

Br

N H

O

344 Dibromopyrrole acid 4,5-Dibromo-1H-pyrrole-2-carboxylic acid Type: Simple pyrrole alkaloids. C5H3Br2NO2 mp 148 °C (sublimation). Source: Sponges Axinella sp. (Australia), Agelas oroides, Agelas clathrodes, Agelas conifera and Agelas flabelliformis. Pharm: Immunosuppressive (potent in vitro); antifeedant. Ref: S. Forenza, et al, Chem. Commun., 1971, 1129│ R. A. Barrow, et al, Nat. Prod. Lett., 1992, 1, 243

126

3 Pyrrole Indole and Imidazole Alkaloids

Br O Br

N H

OH

345 4,5-Dibromo-1H-pyrrole-2-carboxamide Type: Simple pyrrole alkaloids. C5H4Br2N2O mp 164–166 °C. Source: Sponges Agelas mauritiana, Agelas oroides, Acanthella carteri, Phakellia fusca and Pseudoceratina purpurea. Pharm: Antifeedant (deterrent for ascidians); larval metamorphosispromoting activity. Ref: S. Forenza, et al, Chem. Commun., 1971, 1129│ S. Tsukamoto, et al, Tetrahedron, 1996, 52, 8181 Br NH2

Br

N O

H

346 Heronapyrrole A Type: Simple pyrrole alkaloids. C20H34N2O6 Yellow oil, [α]D = +16.9° (c = 0.05, MeOH). Source: Marine-derived streptomycete Streptomyces sp. CMB-M0423 (beach sand, Heron I., Australia). Pharm: Antibacterial (gram-positive bacteria). Ref: R. Raju, et al, Org. Lett., 2010, 12, 5158 OH S

O N O

R

O OH

OH N H

347 Heronapyrrole B Type: Simple pyrrole alkaloids. C19H32N2O6 Yellow oil, [α]D = +33.3° (c = 0.05, MeOH). Source: Marine-derived streptomycete Streptomyces sp. CMB-M0423 (beach sand, Heron I., Australia). Pharm: Antibacterial (gram-positive bacteria). Ref: R. Raju, et al, Org. Lett., 2010, 12, 5158 OH S

O N O

R

OH N H

OH OH

3.1 Pyrrole Alkaloids

127

348 Heronapyrrole C Type: Simple pyrrole alkaloids. C19H30N2O6 Source: Marine-derived streptomycete Streptomyces sp. CMB-M0423 (beach sand, Heron I., Australia). Pharm: Antibacterial (gram-positive bacteria). Ref: R. Raju, et al, Org. Lett., 2010, 12, 5158│ J. Schmidt, et al, Org. Lett., 2012, 14, 4042 (structure revised) O O

N

OH

HN

O O HO

8

11 8,11-cis

349 5-Hexadecyl-1H-pyrrole-2-carboxaldehyde Type: Simple pyrrole alkaloids. C21H37NO Source: Sponges Laxosuberites sp and Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration). Ref: D. B. Stierle, et al, JOC, 1980, 45, 4980│ S. -C. Mao, et al, JNP, 2009, 72, 1927 O H N H

350 Ircinamine B Type: Simple pyrrole alkaloids. C26H49NOS Oil. Source: Sponge Dactylia sp. Pharm: Cytotoxic (P388, IC50 = 0.28 μg/mL). Ref: S. Sato, et al, Tet. Lett., 2006, 47, 7871

O

N

S

H

351 Lamellarin R Type: Simple pyrrole alkaloids. C24H19NO5 Green oil. Source: Sponge Dendrilla cactos [Syn. Dendrilla cactus] (New South Wales). Pharm: Antibiotic. Ref: S. Urban, et al, Aust. J. Chem., 1995, 48, 1491

128

3 Pyrrole Indole and Imidazole Alkaloids

HO

O O

N

OH

HO

352 5-(14-Methylpentadecyl)-1H-pyrrole-2-carboxaldehyde Type: Simple pyrrole alkaloids. C21H37NO Source: Sponges Mycale microsigmatosa (Caribbean Sea) and Desmapsamma anchorata (Venezuela). Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration). Ref: R. S. Compagnone, et al, Nat. Prod. Lett., 1999, 13, 203│ S. -C. Mao, et al, JNP, 2009, 72, 1927

O H

N H

12

353 5-(13-Methyltetradecyl)-1H-pyrrole-2-carboxaldehyde Type: Simple pyrrole alkaloids. C20H35NO Source: Sponges Mycale microsigmatosa (Caribbean Sea) and Desmapsamma anchorata (Venezuela). Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 20–30 μmol/L, suppressed mitochondrial respiration). Ref: R. S. Compagnone, et al, Nat. Prod. Lett., 1999, 13, 203│ S. -C. Mao, et al, JNP, 2009, 72, 1927

O H

N H

11

354 Mycalazal 2 Type: Simple pyrrole alkaloids. C30H45NO Colorless oil. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 2 μg/mL, SCHABEL, IC50 = 2 μg/mL, A549, IC50 = 5 μg/mL, HT29, IC50 = 5 μg/mL, MEL28, IC50 = 5 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331; 2004, 60, 2517

H N H O

3.1 Pyrrole Alkaloids

129

355 Mycalazal 3 Type: Simple pyrrole alkaloids. C26H41NO Oil. Source: Sponge Mycale cecilia. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 20–30 μmol/L, suppressed mitochondrial respiration). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331; 2004, 60, 2517│ S. -C. Mao, et al, JNP, 2009, 72, 1927

H N H

8

O

356 Mycalazal 14 Type: Simple pyrrole alkaloids. C19H33NO Powder. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 20–30 μmol/L, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927

H N H O

357 Mycalazal 15 Type: Simple pyrrole alkaloids. C22H37NO Oil. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O H

H N

358 Mycalazal 16 Type: Simple pyrrole alkaloids. C21H35NO Oil. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 20–30 μmol/L, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927

130

3 Pyrrole Indole and Imidazole Alkaloids

O H N

H

359 Mycalazal 17 Type: Simple pyrrole alkaloids. C21H35NO Oil. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 20–30 μmol/L, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O H N H

360 Mycalazal 18 Type: Simple pyrrole alkaloids. C22H35NO Oil. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 20–30 μmol/L, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 13

O H N H 10

361 Mycalazal 19 Type: Simple pyrrole alkaloids. C22H33NO Oil. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927

H

N H O

4

3.1 Pyrrole Alkaloids

131

362 Mycalazal 20 Type: Simple pyrrole alkaloids. C24H37NO Oil. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 20–30 μmol/L, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927

H N H

6

O

363 Mycalazol 1 Type: Simple pyrrole alkaloids. C30H43NO2 Oil. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 2 μg/mL, SCHABEL, IC50 = 2 μg/mL, A549, IC50 = 2 μg/mL, HT29, IC50 = 2 μg/mL, MEL28, IC50 = 2.5 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

HO N H

6

O

364 Mycalazol 2 Type: Simple pyrrole alkaloids. C26H41NO2 Oil. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 2 μg/mL, SCHABEL, IC50 = 2 μg/mL, A549, IC50 = 2 μg/mL, HT29, IC50 = 5 μg/mL, MEL28, IC50 = 5 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

HO N H

3

10

O

365 Mycalazol 3 Type: Simple pyrrole alkaloids. C28H43NO2 Oil. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 2 μg/mL, SCHABEL, IC50 = 2 μg/mL, A549, IC50 = 2 μg/mL, HT29, IC50 = 2.5 μg/mL, MEL28, IC50 = 2.5 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

HO N H O 3

132

3 Pyrrole Indole and Imidazole Alkaloids

366 Mycalazol 4 Type: Simple pyrrole alkaloids. C24H41NO2 Cryst. (MeOH), mp 68–70 °C. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 2 μg/mL, SCHABEL, IC50 = 2 μg/mL, A549, IC50 = 2 μg/mL, HT29, IC50 = 2.5 μg/mL, MEL28, IC50 = 2.5 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

N H O

OH

367 Mycalazol 5 Type: Simple pyrrole alkaloids. C30H45NO2 Oil. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 2 μg/mL, SCHABEL, IC50 = 2 μg/mL, A549, IC50 = 2 μg/mL, HT29, IC50 = 2.5 μg/mL, MEL28, IC50 = 2.5 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

OH

N H O

368 Mycalazol 6 Type: Simple pyrrole alkaloids. C26H43NO2 Oil. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 1 μg/mL, SCHABEL, IC50 = 1 μg/mL, A549, IC50 = 1 μg/mL, HT29, IC50 = 1 μg/mL, MEL28, IC50 = 2 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

N H OH

O

369 Mycalazol 7 Type: Simple pyrrole alkaloids. C23H41NO2 Oil. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 1 μg/mL, SCHABEL, IC50 = 1 μg/mL, A549, IC50 = 1 μg/mL, HT29, IC50 = 2 μg/mL, MEL28, IC50 = 2 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

N H OH

O

3.1 Pyrrole Alkaloids

133

370 Mycalazol 8 Type: Simple pyrrole alkaloids. C28H45NO2 Oil. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 2 μg/mL, SCHABEL, IC50 = 2 μg/mL, A549, IC50 = 2 μg/mL, HT29, IC50 = 5 μg/mL, MEL28, IC50 = 2.5 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

N H OH

O

371 Mycalazol 9 Type: Simple pyrrole alkaloids. C30H47NO2 Oil. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 2 μg/mL, SCHABEL, IC50 = 2 μg/mL, A549, IC50 = 2 μg/mL, HT29, IC50 = 2 μg/mL, MEL28, IC50 = 2 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

N H OH

O

372 Mycalazol 10 Type: Simple pyrrole alkaloids. C26H45NO2 Cryst. (MeOH), mp 74–76 °C. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 2 μg/mL, SCHABEL, IC50 = 2 μg/mL, A549, IC50 = 2 μg/mL, HT29, IC50 = 2.5 μg/mL, MEL28, IC50 = 2.5 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

OH

N H O

373 Mycalazol 11 Type: Simple pyrrole alkaloids. C24H43NO2 Amorph. powder. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 2.5 μg/mL, SCHABEL, IC50 = 2.5 μg/mL, A549, IC50 = 1 μg/mL, HT29, IC50 = 10 μg/mL, MEL28, IC50 = 10 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

N H OH

O

134

3 Pyrrole Indole and Imidazole Alkaloids

374 Mycalazol 12 Type: Simple pyrrole alkaloids. C28H47NO2 Oil. Source: Sponge Mycale micracanthoxea (Spain). Pharm: Cytotoxic (P388, IC50 = 1 μg/mL, SCHABEL, IC50 = 2 μg/mL, A549, IC50 = 1 μg/mL, HT29, IC50 = 10 μg/mL, MEL28, IC50 = 5 μg/mL). Ref: M. J. Ortega, et al, Tetrahedron, 1997, 53, 331

N H O

OH

375 Mycalenitrile 1 5-Formyl-1H-pyrrole-2-octadecanenitrile Type: Simple pyrrole alkaloids. C23H38N2O Source: Sponge Mycale cecilia. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 10–20 μmol/L, suppressed mitochondrial respiration). Ref: M. J. Ortega, et al, Tetrahedron, 2004, 60, 2517│ S. -C. Mao, et al, JNP, 2009, 72, 1927 O

H N

H

N

376 Mycalenitrile 2 5-Formyl-1H-pyrrole-2-heneicosanenitrile Type: Simple pyrrole alkaloids. C26H44N2O Oil. Source: Sponge Mycale cecilia. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration). Ref: M. J. Ortega, et al, Tetrahedron, 2004, 60, 2517│ S. -C. Mao, et al, JNP, 2009, 72, 1927 O

H N

H

N

377 Mycalenitrile 4 Type: Simple pyrrole alkaloids. C29H46N2O Powder. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter

3.1 Pyrrole Alkaloids

135

assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration). Ref: M. J. Ortega, et al, Tetrahedron, 2004, 60, 2517│ S. -C. Mao, et al, JNP, 2009, 72, 1927 O H N H 2

14

N

378 Mycalenitrile 5 Type: Simple pyrrole alkaloids. C29H46N2O Viscous liq. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 10–20 μmol/L, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O H N H

12

2

2

N

379 Mycalenitrile 6 Type: Simple pyrrole alkaloids. C25H38N2O Oil. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 7.8 μmol/L, suppressed mitochondrial respiration by blocking NADH-ubiquinone oxidoreductase). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O H N H

8

2

2

N

380 Mycalenitrile 7 Type: Simple pyrrole alkaloids. C25H42N2O Oil. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 8.6 μmol/L, suppressed mitochondrial respiration by blocking NADH-ubiquinone oxidoreductase). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O H N H

10

2

2

N

381 Mycalenitrile 8 Type: Simple pyrrole alkaloids. C25H40N2O Yellow solid, mp 42–44 °C. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-

136

3 Pyrrole Indole and Imidazole Alkaloids

based HIF-1 activation reporter assay, IC50 = 10–20 μmol/L, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O H N H

9

4

1

N

382 Mycalenitrile 9 Type: Simple pyrrole alkaloids. C27H44N2O Oil. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O

H N

H

11

4

1

N

383 Mycalenitrile 10 5-(23-Cyano-16-tricosenyl)-1H-pyrrole-2-carboxaldehyde Type: Simple pyrrole alkaloids. C29H48N2O mp 42–45 °C. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O

H N

H

13

4

1

N

384 Mycalenitrile 11 Type: Simple pyrrole alkaloids. C27H44N2O Oil. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O H

H N 4

1

11

N

385 Mycalenitrile 12 Type: Simple pyrrole alkaloids. C28H46N2O Oil. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation

3.1 Pyrrole Alkaloids

137

reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O H N H

4

1

12

N

386 Mycalenitrile 13 Type: Simple pyrrole alkaloids. C21H34N2O mp 73–75 °C. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, IC50 = 10–20 μmol/L, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O H N H

N

387 Mycalenitrile 14 Type: Simple pyrrole alkaloids. C24H40N2O mp 74–77 °C. Source: Sponge Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial respiration). Ref: S. -C. Mao, et al, JNP, 2009, 72, 1927 O H N H

N

388 Nitropyrrolin A Type: Simple pyrrole alkaloids. C19H30N2O4 Light yellow oil, [α]D20 = +8° (c = 0.05, CH2Cl2). Source: An unidentified marine-derived actinomycete CNQ-509. Pharm: Cytotoxic (HCT116, IC50 = 31.1 μmol/L); antibacterial (MRSA, > 20 μg/mL). Ref: H. C. Kwon, et al, JNP, 2010, 73, 2047 OH S

R

O

OH N O

N H

138

3 Pyrrole Indole and Imidazole Alkaloids

389 Nitropyrrolin B‡ Type: Simple pyrrole alkaloids. C19H28N2O3 Light yellow oil, [α]D20 = +3° (c = 0.05, CH2Cl2). Source: An unidentified marine-derived actinomycete CNQ-509. Pharm: Cytotoxic (HCT116, IC50 = 31.0 μmol/L); antibacterial (MRSA, > 20 μg/mL). Ref: H. C. Kwon, et al, JNP, 2010, 73, 2047

R R

O

O N O

N H

390 Nitropyrrolin C Type: Simple pyrrole alkaloids. C19H25ClN2O3 Light yellow oil, [α]D20 = −2° (c = 0.07, CH2Cl2). Source: An unidentified marine-derived actinomycete CNQ-509. Pharm: Cytotoxic (HCT116, > 20 μg/mL); antibacterial (MRSA, > 20 μg/mL). Ref: H. C. Kwon, et al, JNP, 2010, 73, 2047

R

Cl

R

O

OH N O

N H

391 Nitropyrrolin D Type: Simple pyrrole alkaloids. C19H28N2O3 Light yellow oil, [α]D20 = −9° (c = 0.003, MeOH). Source: An unidentified marine-derived actinomycete CNQ-509. Pharm: Cytotoxic (HCT116, IC50 = 5.7 μmol/L); antibacterial (MRSA, > 20 μg/mL). Ref: H. C. Kwon, et al, JNP, 2010, 73, 2047

3E R

O N O

OH N H

392 Nitropyrrolin E Type: Simple pyrrole alkaloids. C19H31ClN2O5 Light yellow oil, [α]D20 = +15° (c = 0.002, MeOH). Source: An unidentified marine-derived actinomycete CNQ-509. Pharm: Cytotoxic (HCT116, > 20 μg/mL); antibacterial (MRSA, > 20 μg/mL). Ref: H. C. Kwon, et al, JNP, 2010, 73, 2047

3.1 Pyrrole Alkaloids

139

Cl R R

O

R

N

OH OH

OH N H

O

393 Palmyrrolinone Type: Simple pyrrole alkaloids. C12H15NO4 Source: Cyanobacteria Oscillatoria cf. and Hormoscilla spp. (assemblage, North Beach, Palmyra Atoll). Pharm: Molluscacidal (snail Biomphalaria glabrata, potent). Ref: A. R. Pereira, et al, JNP, 2011, 74, 1175 O

N

OH

O

O

394 Pentabromopseudilin Type: Simple pyrrole alkaloids. C10H4Br5NO Cryst. (C6H6/hexane), mp 130–170 °C (dec). Source: Marine bacterium Pseudomonas bromoutilis from marine bacterium Chromobacterium sp. (yellow and off-white strains, major metabolite). Pharm: Antibacterial (gram-positive bacteria), esterases inhibitor; aminopeptidases inhibitor; elastase inhibitor; urokinase inhibitor; alkaline phosphatase inhibitor; LD50 (mus, ivn) = 25–75 mg/kg, LD50 (mus, scu) = 250–350 mg/kg, LD50 (mus, ipr) = 50 mg/kg. Ref: P. R. Burkholder, et al, Appl. Microbiol., 1966, 14, 649│ R. J. Andersen, et al, Mar. Biol., 1974, 27, 281│ H. Laatsch, et al, Liebigs Ann. Chem., 1989, 863│ CRC Press, DNP on DVD, 2012, version 20.2 Br

Br OH Br N H

Br

Br

395 5-Pentadecyl-1H-pyrrole-2-carboxaldehyde Type: Simple pyrrole alkaloids. C20H35NO Source: Sponges Laxosuberites sp and Mycale sp. Pharm: HIF-1 activation inhibitor (hmn breast tumour T47D cell-based HIF-1 activation reporter assay, 30 μmol/L, InRt < 50%, suppressed mitochondrial

140

3 Pyrrole Indole and Imidazole Alkaloids

respiration). Ref: D. B. Stierle, et al, JOC, 1980, 45, 4980│ S. -C. Mao, et al, JNP, 2009, 72, 1927 O

H N

H

396 2,3,4-Tribromo-1H-pyrrole Type: Simple pyrrole alkaloids. C4H2Br3N Pale yellow oil. Source: Annelid polychaete worm Polyphysia crassa and Saccoglossus kowalevskii. Pharm: Antibacterial; antifeedant. Ref: R. Emrich, et al, JNP, 1990, 53, 703│ C. E. Kicklighter, et al, Limnol. Oceanogr., 2004, 49, 430 Br

Br

Br

N H

397 Lamellarin A Type: Lamellarins. C30H27NO10 Pale yellow prisms (MeOH), mp 168–172 °C (dec). Source: Prosobranch Lamellaria sp. (depth of 5 m, near Koror, Palau). Pharm: MDR inhibitor; immunomodulator. Ref: R. J. Andersen, et al, JACS, 1985, 107, 5492 O

O

O

OH

20

5

21

HO

6

N

O 7

HO

13

12

O

9

O

O

398 Lamellarin A1 Type: Lamellarins. C27H21NO8 Source: Ascidians Didemnum sp. (Wasp I., New South Wales; Northern Rottnest Shelf, Western Australia). Pharm: Cytotoxic (hmn carcinoma cell line, P-gp-overexpression variant, doxorubicin (P-gp substrate)). Ref: F. Plisson, et al, Chem. Asian J., 2012, 7, 1616

3.1 Pyrrole Alkaloids

HO

HO

141

OH

O

O

O N

O HO

5

399 Lamellarin A2 Type: Lamellarins. C28H23NO9 Source: Ascidians Didemnum sp. (Wasp I., New South Wales; Northern Rottnest Shelf, Western Australia). Pharm: Cytotoxic (hmn carcinoma cell line, P-gp-overexpression variant, doxorubicin (P-gp substrate)). Ref: F. Plisson, et al, Chem. Asian J., 2012, 7, 1616 HO

HO

OH

O O

O N

O O

5

OH

400 Lamellarin A3 Type: Lamellarins. C29H25NO8 Source: Ascidians Didemnum sp. (Wasp I., New South Wales; Northern Rottnest Shelf, Western Australia). Pharm: Cytotoxic (hmn carcinoma cell line, P-gp-overexpression variant, doxorubicin (P-gp substrate)). Ref: F. Plisson, et al, Chem. Asian J., 2012, 7, 1616 O

HO

OH

O O

O N

O O

5

401 Lamellarin A4 Type: Lamellarins. C25H17NO8 Source: Ascidians Didemnum sp. (Wasp I., New South Wales; Northern Rottnest Shelf, Western Australia). Pharm: Cytotoxic (hmn carcinoma

142

3 Pyrrole Indole and Imidazole Alkaloids

cell line, P-gp-overexpression variant, doxorubicin (P-gp substrate)). Ref: F. Plisson, et al, Chem. Asian J., 2012, 7, 1616 HO

HO

OH

HO

O

HO N

O

HO

5

402 Lamellarin A5 Type: Lamellarins. C26H17NO8 Source: Ascidians Didemnum sp. (Wasp I., New South Wales; Northern Rottnest Shelf, Western Australia). Pharm: Cytotoxic (hmn carcinoma cell line, P-gp-overexpression variant, doxorubicin (P-gp substrate)). Ref: F. Plisson, et al, Chem. Asian J., 2012, 7, 1616 HO

HO

OH

O O

HO N

O HO

5

403 Lamellarin A6 Type: Lamellarins. C28H23NO8 Source: Ascidians Didemnum sp. (Wasp I., New South Wales; Northern Rottnest Shelf, Western Australia). Pharm: Cytotoxic (hmn carcinoma cell line, P-gp-overexpression variant, doxorubicin (P-gp substrate)). Ref: F. Plisson, et al, Chem. Asian J., 2012, 7, 1616 HO

HO

O

O O

O N

O HO

5

3.1 Pyrrole Alkaloids

143

404 Lamellarin B Type: Lamellarins. C30H25NO9 Pale yellow needles (MeOH), mp 258–259 °C. Source: Prosobranch Lamellaria sp. (depth of 5 m, near Koror, Palau). Pharm: Immunomodulator. Ref: R. J. Andersen, et al, JACS, 1985, 107, 5492 HO

20

O

21

O

O

N

5 6

O 7 9 8

13

HO

O

12

O

O

405 Lamellarin C Dihydrolamellarin B Type: Lamellarins. C30H27NO9 Needles (MeOH), mp 225–230 °C. Source: Prosobranch Lamellaria sp. (depth of 5 m, near Koror, Palau). Pharm: Cell division inhibitor (fertilised sea urchin eggs, 19 μg/mL, InRt = 15%). Ref: R. J. Andersen, et al, JACS, 1985, 107, 5492 HO

20

O

21

O

O

N

5 6

O 7 9 8

13

HO

O

12

O

O

406 Lamellarin D Type: Lamellarins. C28H21NO8 Pale yellow powder. Source: Prosobranch Lamellaria sp. (depth of 5 m, near Koror, Palau). Pharm: Cell division inhibitor (fertilised sea urchin eggs, 19 μg/mL, InRt = 78%). Ref: R. J. Andersen, et al, JACS, 1985, 107, 5492 O

HO

O

N

O

OH HO

O

O

144

3 Pyrrole Indole and Imidazole Alkaloids

407 Lamellarin I Type: Lamellarins. C31H29NO9 Off-white irregular prisms (MeOH), mp 218–220 °C. Source: Ascidian Didemnum sp. (Australia). Pharm: MDR inhibitor. Ref: A. R. Carroll, et al, Aust. J. Chem., 1993, 46, 489 HO

O

O

O

N

O O O O

O

408 Lamellarin J Type: Lamellarins. C29H25NO8 Amorph. powder, mp 216–220 °C. Source: Prosobranch Lamellaria sp., ascidian Didemnum sp. Pharm: Immunomodulator. Ref: A. R. Carroll, et al, Aust. J. Chem., 1993, 46, 489 HO

O

O

20 5

21

6

O

N

7

O

13

12

OH

9

O

O

409 Lamellarin K Type: Lamellarins. C29H25NO9 Amorph. powder, mp 196–198 °C. Source: Ascidian Didemnum sp. Pharm: Immunomodulator. Ref: A. R. Carroll, et al, Aust. J. Chem., 1993, 46, 489 HO

O

O

20 5

21

6

O

N

OH 7

HO

13

12

O

9

O

O

3.1 Pyrrole Alkaloids

145

410 Lamellarin M Type: Lamellarins. C29H23NO9 Amorph. powder. Source: Prosobranch Lamellaria sp., ascidian Didemnum sp. Pharm: Immunomodulator. Ref: A. R. Carroll, et al, Aust. J. Chem., 1993, 46, 489 O

HO

O

20 5

21

6

O

N

OH 7

HO

13

12

O

9

O

O

411 Lamellarin α 20-sulfate Type: Lamellarins. C29H23NO11S Solid (Na salt), mp 145–148 °C (Na salt). Source: Prosobranch Lamellaria sp. Pharm: Integrase (IN) inhibitor (terminate cleavage activity, IC50 = 16 μmol/L); HIV-1 integrase inhibitor (HIV encodes three enzymes, reverse transcrptase RT, protease PR and integrase IN). Ref: M. V. R. Reddy, et al, JMC, 1999, 42, 1901 O O

H

S

O

O

O

O

O

N

HO

O

O O

412 Lamellarin β Type: Lamellarins. C26H19NO8 Amorph. solid Source: Ascidian Didemnum sp. Pharm: Cytotoxic. Ref: J. Ham, et al, Bull. Korean Chem. Soc., 2002, 23, 163 HO

20

HO

21

O

O

N

5 6

7 9 8

13

O

OH

12

OH

OH

146

3 Pyrrole Indole and Imidazole Alkaloids

413 Antibiotic BE 18591 Type: Miscellaneous pyrrole alkaloids. C22H35N3O Yellowish-green amorph. solid, mp 50–53 °C. Source: Marine-derived streptomycete Streptomyces sp. BA18591. Pharm: Antineoplastic. Ref: K. Kojiri, et al, J. Antibiot., 1993, 46, 1799; 1894 O H N N

N H

414 Dictyodendrin J Type: Miscellaneous pyrrole alkaloids. C34H24N2O8 Source: Sponge Ianthella sp. (Bass Strait, Australia). Pharm: β-Secretase (BACE) inhibitor (modest); antiAlzheimer's agents (potential). Ref: H. Zhang, et al, RSC Adv., 2012, 2, 4209 HO

H N

O

O

O OH

N OH

O

HO

415 Keronopsin A1 Type: Miscellaneous pyrrole alkaloids. C18H16BrNO6S Brick-red amorph. powder (Na salt). Source: Protist ciliate Pseudokeronopsis riccii. Pharm: Chemical defence substance. Ref: G. Höfle, et al, Angew. Chem., Int. Ed. Engl., 1994, 33, 1495 Br

O N H

O

H

S

O

O O O

416 Keronopsin A2 Type: Miscellaneous pyrrole alkaloids. C18H15Br2NO6S Source: Protist ciliate Pseudokeronopsis riccii. Pharm: Chemical defence substance. Ref: G. Höfle, et al, Angew. Chem., Int. Ed. Engl., 1994, 33, 1495

3.1 Pyrrole Alkaloids

Br

147

Br

O N H

O

H

S

O

O O O

417 Keronopsin B1 Type: Miscellaneous pyrrole alkaloids. C18H16BrNO3 Black cryst. (Me2CO), mp 135–139 °C. Source: Protist ciliate Pseudokeronopsis riccii. Pharm: Chemical defence substance. Ref: G. Höfle, et al, Angew. Chem., Int. Ed. Engl., 1994, 33, 1495 Br

OH N H O

O

418 Keronopsin B2 Type: Miscellaneous pyrrole alkaloids. C18H15Br2NO3 Brown-red amorph. powder. Source: Protist ciliate Pseudokeronopsis riccii. Pharm: Chemical defence substance. Ref: G. Höfle, et al, Angew. Chem., Int. Ed. Engl., 1994, 33, 1495 Br

Br

OH N H O

O

419 Lukianol A Type: Miscellaneous pyrrole alkaloids. C25H17NO5 Amorph. powder (MeOH), mp 264–266 °C. Source: An unidentified ascidian (encrusting, Palmyra Atoll). Pharm: Cytotoxic (KB, MIC = 1 μg/mL); MDR reversing agent. Ref: R. T. Luibrand, et al, Tetrahedron, 1979, 35, 609│ W. Y. Yoshida, et al, Helv Chim. Acta, 1992, 75, 1721│ A. Terpin, et al, Tetrahedron, 1995, 51, 9941│ D. L. Boger, et al, JACS, 1999, 121, 54

148

3 Pyrrole Indole and Imidazole Alkaloids

HO OH

O N O

OH

420 Lukianol B Type: Miscellaneous pyrrole alkaloids. C25H16INO5 Off-white powder (MeOH). Source: An unidentified ascidian (encrusting, Palmyra Atoll). Pharm: Cytotoxic. Ref: W. Y. Yoshida, et al, Helv. Chim. Acta. 1992, 75, 1721 HO

I

OH

3'

O N O

OH

421 Marineosin A Type: Miscellaneous pyrrole alkaloids. C25H35N3O2 Oil, [α]D = −101.7° (c = 0.06, MeOH). Source: Marine-derived streptomycete Streptomyces sp. CNQ-617. Pharm: Cytotoxic (HCT116, IC50 = 0.5 μmol/L); cytotoxic (NCI’s 60 cell line panel, broad cytotoxicity with considerable selectivity against melanoma and leukemia cell lines); antifungal (Candida albicans, MIC > 100 μg/mL, extremely weak). Ref: C. Boonlarppradab, et al, Org. Lett., 2008, 10, 5505

3.1 Pyrrole Alkaloids

N H

149

O 7

N O

8

H

N H

H

422 Marineosin B Type: Miscellaneous pyrrole alkaloids. C25H35N3O2 Oil, [α]D = +143.5° (c = 0.09, MeOH). Source: Marine-derived streptomycete Streptomyces sp. CNQ-617. Pharm: Cytotoxic (HCT116, IC50 = 46 μmol/L); Antifungal (Candida albicans, MIC > 100 μg/mL, extremely weak). Ref: C. Boonlarppradab, et al, Org. Lett., 2008, 10, 5505

N H

O 7

N O

N H

8

H H

423 Marinopyrrole A Type: Miscellaneous pyrrole alkaloids. C22H12Cl4N2O4 [α]D = −69° (c = 0.39, MeOH). Source: Marine-derived streptomycete Streptomyces sp. CNQ-418 (sediment, optimisation of culture conditions La Jolla, California). Pharm: Antibacterial (MRSA, MIC90 = 0.31 μg/mL, control Vancomycin, MIC90 = 0.20–0.39 μg/mL, control penicillin G, MIC90 = 6.3–12 μg/mL); cytotoxic (HCT116, IC50 = 4.5 μg/mL, control Etoposide, 0.29–2.9 μg/mL). Ref: C. C. Hughes, et al, JOC, 2010, 75, 3240 Cl Cl O

N OH

OH

O Cl Cl

N H

424 Marinopyrrole B Type: Miscellaneous pyrrole alkaloids. C22H11BrCl4N2O4 [α]D = −72° (c = 0.2, MeOH). Source: Marine-derived streptomycete Streptomyces sp. CNQ-418 (sediment, optimisation of culture conditions La Jolla, California). Pharm: Antibacterial (MRSA,

150

3 Pyrrole Indole and Imidazole Alkaloids

MIC90 = 0.63 μg/mL, control Vancomycin, MIC90 = 0.20–0.39 μg/mL, penicillin G, MIC90 = 6.3–12 μg/mL); cytotoxic (HCT116, IC50 = 5.3 μg/mL, control Etoposide, 0.29–2.9 μg/mL). Ref: C. C. Hughes, et al, JOC, 2010, 75, 3240 Br

Cl Cl O

N OH

OH

O Cl N H

Cl

425 (–)-Marinopyrrole C Type: Miscellaneous pyrrole alkaloids. C22H11Cl5N2O4 [α]D = −100° (c = 0.04, MeOH). Source: Marine-derived streptomycete Streptomyces sp. CNQ-418 (deep ocean sediment sample, off coast of La Jolla, CA). Pharm: Antibacterial (MRSA, MIC90 = 0.16 μg/mL; control Vancomycin, MIC90 = 0.20–0.39 μg/mL; Penicillin G, MIC90 = 6.3–12 μg/mL); cytotoxic (HCT116, IC50 = 0.21 μg/mL; control Etoposide, IC50 = 0.29–2.9 μg/mL). Ref: C. C. Hughes, et al, JOC, 2010, 75, 3240 5''

Cl

4

Cl

N OH

OH

O

O Cl

5'''

N H

Cl

Cl

426 (±)-Marinopyrrole F Type: Miscellaneous pyrrole alkaloids. C22H11Cl3N2O4 White solid, [α]D = 0° (c = 0.057, MeOH:Me2CO, 2:1). Source: Marine-derived streptomycete Streptomyces sp. CNQ-418 (sediment, optimisation of culture conditions La Jolla, California). Pharm: Antibacterial (MRSA, MIC90 = 3.1 μg/mL, control Vancomycin, MIC90 = 0.20–0.39 μg/mL, penicillin G, MIC90 = 6.3–12 μg/mL); cytotoxic (HCT116, IC50 = 2.9 μg/mL, control Etoposide, 0.29–2.9 μg/mL). Ref: C. C. Hughes, et al, JOC, 2010, 75, 3240 Cl

OH

O N O Cl Cl

N H

O

3.1 Pyrrole Alkaloids

151

427 4-Methoxy-5-[(3-methoxy-5-pyrrol-2-yl-2H-pyrrol-2-ylidene)methyl]2,2′-bipyrrole Type: Miscellaneous pyrrole alkaloids. C19H18N4O2 Blue cryst. (CH2Cl2/petrol) (hydrochloride), mp 300 °C (dec). Source: Bryozoans Bugula neritina and Bugula dentata, nudibranch Nembrotha kubaryana. Pharm: Cytotoxic (CaCo-2, IC50 = (91 ± 15)μmol/L; HeLa, IC50 = (70 ± 18)μmol/L; C6, IC50 = (7 ± 4.2)μmol/L; H9c2, IC50 = (107 ± 8)μmol/L; 3T3-L1, IC50 = (24 ± 8.5)μmol/L); antibacterial (gram-positive bacteria, mild). Ref: H. H. Wasserman, et al, Tet. Lett., 1968, 641│ R. Kazlauskas, et al, Aust. J. Chem., 1982, 35, 215│ S. Matsunaga, et al, Experientia, 1986, 42, 84│ M. Carbone, et al, BoMCL, 2010, 20, 2668

O

N H

O

N

N H

N H

428 Storniamide A Type: Miscellaneous pyrrole alkaloids. C42H35N3O11 Yellow oil. Source: Sponge Cliona sp. (burrowing sponge, Punta Verda, near San Antonio Oeste, Rio negro, Argentina). Pharm: Antibacterial (gram-positive bacteria: Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus, 50 μg/disk). Ref: J. A. Palermo, et al, Tetrahedron, 1996, 52, 2727 OH

OH

OH

HO HO

OH H N

H N

N O

O

HO

OH

OH

429 Storniamide B Type: Miscellaneous pyrrole alkaloids. C42H35N3O12 Yellow oil. Source: Sponge Cliona sp. (burrowing sponge, Punta Verda, near San Antonio Oeste, Rio negro, Argentina). Pharm: Antibacterial (gram-positive bacteria: Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus, 50 μg/disk). Ref: J. A. Palermo, et al, Tetrahedron, 1996, 52, 2727

152

3 Pyrrole Indole and Imidazole Alkaloids

OH

OH

OH

HO HO

OH H N

H N

N O

O

HO

OH OH

OH

430 Storniamide C Type: Miscellaneous pyrrole alkaloids. C42H35N3O12 Yellow oil. Source: Sponge Cliona sp. (burrowing sponge, Punta Verda, near San Antonio Oeste, Rio negro, Argentina). Pharm: Antibacterial (gram-positive bacteria: Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus, 50 μg/disk). Ref: J. A. Palermo, et al, Tetrahedron, 1996, 52, 272 7 OH

OH

OH

HO

H

HO H N

H N

N O

O OH

HO OH

OH

OH

431 Storniamide D Type: Miscellaneous pyrrole alkaloids. C42H35N3O13 Yellow oil. Source: Sponge Cliona sp. (burrowing sponge, Punta Verda, near San Antonio Oeste, Rio negro, Argentina). Pharm: Antibacterial (gram-positive bacteria: Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus, 50 μg/disk). Ref: J. A. Palermo, et al, Tetrahedron, 1996, 52, 2727

3.1 Pyrrole Alkaloids

153

OH

OH

OH

HO HO H N

H N

N O

O

HO

OH

OH OH

OH

OH

432 Stylissadine A Flabellazole B； Dimer of Massadine Type: Miscellaneous pyrrole alkaloids. C44H46Br8N20O9 [α]D22 = −15.2° (c = 1.21, MeOH). Source: Sponges Stylissa caribica and Stylissa flabellata. Pharm: P2X7 receptor inhibitor (specific); reduction of voltage-dependent Ca2+ entry (IC50 = 4.5 μmol/L, MMOA: irreversible effect requiring lipophilic brominated side chain). Ref: A. Grube, et al, Org. Lett., 2006, 8, 4675│ M. S. Buchanan,et al, Org. Chem. 2007, 72, 2309│ M. S. Buchanan, et al, JNP, 2007, 70, 1827│ U. Bickmeyer, et al, Toxicon 2007, 50, 490 Br

NH HN

Br

H O H

NH OH

H

N H

H N

Br

HN

O H N

N H

O O

O

H N

HN H N

O

2

O

Br

N H

HN H

Br

N H

HN

H

OH

N H

Br H N

NH H

Br

N H NH

Br

433 Stylissadine B Flabellazole A Type: Miscellaneous pyrrole alkaloids. C44H46Br8N20O9 [α]D22 = −20° (c = 0.62, MeOH). Source: Sponges Axinella sp. (deep water, Great Australian Bight),

154

3 Pyrrole Indole and Imidazole Alkaloids

Stylissa caribica and Stylissa flabellata. Pharm: Antibacterial (Staphylococcus aureus ATCC 25923, IC50 = 0.64 μmol/L, Staphylococcus aureus ATCC 9144, IC50 = 2.5 μmol/L, Bacillus subtilis ATCC 6051, IC50 = 2.2 μmol/L, Bacillus subtilis ATCC 6633, IC50 = 0.50 μmol/L, Escherichia coli ATCC 11775, IC50 = 0.92 μmol/L, Pseudomonas aeruginosa ATCC 10145, IC50 = 1.3 μmol/L); antifungal (Candida albicans ATCC 90028, IC50 = 6.8 μmol/L); P2X7 receptor inhibitor (specific); reduction of voltage-dependent Ca2+ entry (IC50 = 4.5 μmol/L, MMOA: irreversible effect requiring lipophilic brominated side chain). Ref: A. Grube, et al, Org. Lett., 2006, 8, 4675│ M. S. Buchanan, et al, JOC, 2007, 72, 2309│ M. S. Buchanan, et al, JNP, 2007, 70, 1827│ U. Bickmeyer, et al, Toxicon, 2007, 50, 490│ H. Zhang, et al, Tet. Lett., 2012, 53, 3784 Br Br

NH H

HN NH

NH

O

OH H N H

H HN

H N

N H

HN

Br N H O O

O HN

Br O

H N

H N

Br

N H

HN 2

H O H

O

H N OH H NH

Br H N

N H

Br NH Br

434 Tambjamine A Type: Miscellaneous pyrrole alkaloids. C10H11N3O Oil. Source: Bryozoan Bugula longissima (psychrophilic, cold water, Antarctic), an unidentified bryozoan (tropical), nudibranches Tambja abdere, Tambja eliora, Atapozoa sp., Nembrotha crista, Nembrotha kubaryana and Roboastra tigris, bryozoan Sessibugula translucens (dietary source of nudibranches). Pharm: Antimicrobial; cytotoxic; DNA binding agent. Ref: B. Carlé, et al, JOC, 1983, 48, 2314│ B. Carté, et al, J. Chem. Ecol., 1986, 12, 795│ N. Lindquist, et al, Experientia, 1991, 47, 504│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)│ CRC Press, DNP on DVD, 2012, version 20.2 O

N H

N

NH2

3.1 Pyrrole Alkaloids

155

435 Tambjamine B Type: Miscellaneous pyrrole alkaloids. C10H10BrN3O Oil, Sol. MeOH, CHCl3; poorly sol. H2O. Source: Nudibranches Tambja abdere (Sea of Cortez), Tambja eliora and Roboastra tigris, bryozoan Sessibugula translucens. Pharm: Antimicrobial; cytotoxic; DNA binding agent. Ref: B. Carlé, et al, JOC, 1983, 48, 2314│ B. Carté, et al, J. Chem. Ecol., 1986, 12, 795│ N. Lindquist, et al, Experientia, 1991, 47, 504 O

N H

Br

N

NH2

436 Tambjamine C Type: Miscellaneous pyrrole alkaloids. C14H19N3O Oil, Sol. MeOH, CHCl3; poorly sol. H2O. Source: Nudibranches Tambja abdere, Tambja eliora, and Roboastra tigris, bryozoans Sessibugula spp., ascidians Atapozoa spp. Pharm: Antimicrobial; cytotoxic; DNA binding agent. Ref: B. Carlé, et al, JOC, 1983, 48, 2314│ B. Carté, et al, J. Chem. Ecol., 1986, 12, 795│ N. Lindquist, et al, Experientia, 1991, 47, 504 O

N H

N HN

437 Tambjamine D Type: Miscellaneous pyrrole alkaloids. C14H18BrN3O Oil, Sol. MeOH, CHCl3; poorly sol. H2O. Source: Bryozoan Sessibugula sp., nudibranches Tambja abdere, Tambja eliora and Roboastra tigris. Pharm: Antimicrobial; cytotoxic; DNA binding agent. Ref: B. Carlé, et al, JOC, 1983, 48, 2314│ B. Carté, et al, J. Chem. Ecol., 1986, 12, 795│ N. Lindquist, et al, Experientia, 1991, 47, 504 Br O

N H

N HN

438 Tambjamine E Type: Miscellaneous pyrrole alkaloids. C12H15N3O Yellow cryst. (CDCl3), mp 68–70 °C. Source: Nudibranches Nembrotha crista and Nembrotha kubaryana, ascidian Atapozoa sp. Pharm: DNA binding agent; antifeedant. Ref: N. Lindquist, et al, Experientia, 1991, 47, 504

156

3 Pyrrole Indole and Imidazole Alkaloids

O

1''

N H

N HN

439 Tambjamine F Type: Miscellaneous pyrrole alkaloids. C18H19N3O Brown oil. Source: Nudibranches Nembrotha crista and Nembrotha kubaryana, ascidian Atapozoa sp. Pharm: DNA binding agent; antifeedant. Ref: N. Lindquist, et al, Experientia, 1991, 47, 504 O

N H

1''

N

HN

440 Tambjamine G Type: Miscellaneous pyrrole alkaloids. C12H14BrN3O Source: Bryozoan Bugula dentata (Tasmania). Pharm: Toxic (brine shrimp). Ref: A. J. Blackman, et al, Aust. J. Chem., 1994, 47, 1625 O 3' 5'

Br

1''

N H

N HN

441 Tambjamine H Type: Miscellaneous pyrrole alkaloids. C13H16BrN3O Source: Bryozoan Bugula dentata (Tasmania). Pharm: Toxic (brine shrimp). Ref: A. J. Blackman, et al, Aust. J. Chem., 1994, 47, 1625 O

Br

N H

N N H

442 Tambjamine I Type: Miscellaneous pyrrole alkaloids. C14H18BrN3O Source: Bryozoan Bugula dentata (Tasmania). Pharm: Toxic (brine shrimp). Ref: A. J. Blackman, et al, Aust. J. Chem., 1994, 47, 1625

3.1 Pyrrole Alkaloids

157

O 3' 5'

1''

Br

N

N H

HN

443 Tambjamine J Type: Miscellaneous pyrrole alkaloids. C15H20BrN3O Source: Bryozoan Bugula dentata (Tasmania). Pharm: Toxic (brine shrimp). Ref: A. J. Blackman, et al, Aust. J. Chem., 1994, 47, 1625 O 3' 5'

Br

1''

N H

N HN

444 Tambjamine K Type: Miscellaneous pyrrole alkaloids. C15H21N3O Source: Bryozoan Bugula dentata, nudibranch Tambja ceutae (Azores, Atlantic Ocean). Pharm: Cytotoxic (CaCo-2, IC50 = (3.5 ± 1.4) × 10−3 μmol/L; HeLa, IC50 = (14.6 ± 9)μmol/L; C6, IC50 = (14 ± 5.4)μmol/L; H9c2, IC50 = (2.7 ± 2)μmol/L; 3T3-L1, IC50 = (19 ± 12)μmol/L). Ref: M. Carbone, et al, BoMCL, 2010, 20, 2668 O

NH

N NH

445 Ageladine A Type: Pyrrole-imidazole alkaloids. C10H7Br2N5 Yellow powder (di–TFA salt). Source: Sponge Agelas nakamurai. Pharm: Antiangiogenic matrixmetalloproteinase inhibitor. Ref: M. Fujita, et al, JACS, 2003, 125, 15700 Br

Br

N N H N N H 2N

H

158

3 Pyrrole Indole and Imidazole Alkaloids

446 (–)-Agelastatin A Type: Pyrrole-imidazole alkaloids. C12H13BrN4O3 [α]D20 = −84.3° (c = 0.3, EtOH) (N, N,O-tri-Me). Source: Sponges Cymbastela sp. (Western Australia) and Agelas dendromorpha (Coral Sea). Pharm: Cytotoxic (KB, EC50 = 0.5–0.1 μg/mL); inhibits proliferation of spleen cells (mus: lymphocyte T ConA-induced, lymphocyte B LPSinduced); antineoplastic; insecticide (larvae of beet army worm Spodoptera exigua and corn rootworm Diabrotica undecimpunctata); toxic (brine shrimp Artemia franciscana, LC50 = 1.7 ppm); prevents metastatic cancer spread. Ref: M. D'Ambrosio, et al, J. Chem. Soc. Chem. Commun., 1993, 1305│ M. D'Ambrosio, et al, Helv. Chim. Acta, 1994, 77, 1895; 1996, 79, 727│ T. W. Hong, et al, JNP, 1998, 61, 158

HO Br

N 6b

H

O NH

H

N H

2

NH O

447 Agelastatin C Type: Pyrrole-imidazole alkaloids. C12H13BrN4O4 Solid, [α]D = −5° (c = 0.06, MeOH). Source: Sponge Cymbastela sp. (Western Australia). Pharm: Cytotoxic; insecticide; toxic (brine shrimp Artemia franciscana, LC50 = 200 ppm). Ref: T. W. Hong, et al, JNP, 1998, 61, 158

HO Br

N

O

6b

H

NH OH

N H

2

NH O

448 Agelastatin D Type: Pyrrole-imidazole alkaloids. C11H11BrN4O3 Solid. Source: Sponge Cymbastela sp. Pharm: Insecticide. Ref: T. W. Hong, et al, JNP, 1998, 61, 158

3.1 Pyrrole Alkaloids

H N

HO Br

159

O

6b

H

NH

N

H H

2

NH O

449 Ageliferin Type: Pyrrole-imidazole alkaloids. C22H24Br2N10O2 [α]D33 = +15.5° (c = 0.11, MeOH). Source: Sponges Agelas sp. SS-1003 (off Seragaki, Okinawa), Agelas nakamurai (with two CF3COO-, yield = 0.0009% ww, Ambon, Indonesia, 1997), Agelas conifera, Agelas novaecaledoniae, Agelas cf. mauritiana and Xestospongia sp. Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 4.17 μg/mL; Bacillus subtilis, MIC = 8.33 μg/mL; gram-negative bacterium Escherichia coli, MIC = 33.3 μg/mL) (Endo, 2004); protein phosphatase 2A inhibitor (IC50 > 50 μmol/L) (Endo, 2004); antibacterial (0.2 μmol/disk: Bacillus subtilis 168, IZD = 14 mm; Staphylococcus aureus ATCC 25923, IZD = 11 mm; Escherichia coli ATCC 25922, IZD = 8 mm; Escherichia coli HB101, IZD = 11 mm) (Eder, 1999); actomyosin ATPase activator; antifoulant; somatostatin antagonist. Ref: J. Kobayashi, et al, Tetrahedron 1990, 46, 5579│ P. A. Keifer, et al, JOC, 1991, 56, 2965; 6728│ A. Vassas, et al, PM, 1996, 62, 28│ C. Eder, et al, JNP, 1999, 62, 1295│ T. Endo, et al, JNP, 2004, 67, 1262 Br H2N N N H

H N

HN

O

Br

N 10

H N N H

NH2 N H

O

450 Axinellamine A Type: Pyrrole-imidazole alkaloids. C22H23Br4ClN10O4 Powder (bistrifluoroacetate salt), [α]D20 = −18° (c = 0.16, MeOH). Source: Sponges Axinella sp. (deep water, Great Australian Bight) and Axinella sp. (Australia). Pharm: Antibacterial (Helicobacter pylori (a gram negative bacterium associated with pepticular and gastric cancer), 1,000 μmol/L). Ref: S. Urban, et al, JOC, 1999, 64, 731│ S. Urban, et al, JOC, 1999, 64, 731│ H. Zhang, et al, Tet. Lett., 2012, 53, 3784

160

3 Pyrrole Indole and Imidazole Alkaloids

H N

HN

1

Br

OH Cl

2''

NH

5

HN 9

H N

N OH H H

HN

Br

N

H

N H

O Br

O N H

2'

Br

451 Axinellamine B Type: Pyrrole-imidazole alkaloids. C22H23Br4ClN10O4 Pale yellow oil, [α]D20 = −7° (c = 0.21, MeOH). Source: Sponges Axinella sp. (deep water, Great Australian Bight) and Axinella sp. (Australia). Pharm: Antibacterial (Bacillus subtilis ATCC 6051, IC50 = 5.0 μmol/L, Bacillus subtilis ATCC 6633, IC50 = 10 μmol/L). Ref: H. Zhang, et al, Tet. Lett., 2012, 53, 3784│ S. Urban, et al, JOC, 1999, 64, 731 H N

HN

1

H

Br

OH

2''

Cl

NH

5

HN 9

HN

Br

N

H N H OH

H N

N H

O Br

O N H

2'

Br

452 Axinellamine C Type: Pyrrole-imidazole alkaloids. C23H25Br4ClN10O4 Pale yellow oil, [α]D20 = −9° (c = 1.1, MeOH). Source: Sponges Axinella sp. (deep water, Great Australian Bight) and Axinella sp. (Australia). Pharm: Antibacterial (Helicobacter pylori (a gram negative bacterium associated with pepticular and gastric cancer), 1,000 μmol/L). Ref: H. Zhang, et al, Tet. Lett., 2012, 53, 3784│ S. Urban, et al, JOC, 1999, 64, 731

3.1 Pyrrole Alkaloids

H N

HN

Br

O

2''

Cl

1

Br

N

H

NH

5

HN 9

H N

N OH H H

HN

161

N H

O Br

O N H

2'

Br

453 (Z)-Axinohydantoin Spongiacidin D Type: Pyrrole-imidazole alkaloids. C11H9BrN4O3 Amorph. solid, mp 221–227 °C (dec). Source: Sponges Stylotella aurantium, Phakellia fusca and Hymeniacidon sp. (Okinawa). Pharm: PKC Inhibitor (IC50 = 9.0 μmol/L). Ref: X. Fu, et al, Chem. Res. Chin. Univ., 1991, 7, 178│ A. D. Patil, et al, Nat. Prod. Lett., 1997, 9, 201│ K. Inaba, et al, JNP, 1998, 61, 693│ W. Li, et al, Zhongguo Haiyang Yaowu, 2001, 20, 9│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) H N

O

O

N H

Z

Br N H

N H O

454 2-Bromoageliferin Type: Pyrrole-imidazole alkaloids. C22H23Br3N10O2 [α]D33 = +8.8° (c = 0.08, MeOH). Source: Sponges Agelas sp. SS-1003 (off Seragaki, Okinawa), Agelas conifera, Agelas cf. mauritiana and Astrosclera willeyana. Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 2.08 μg/mL; Bacillus subtilis, MIC = 2.08 μg/mL; gramnegative bacterium Escherichia coli, MIC = 16.7 μg/mL) (Endo, 2004); protein phosphatase 2A inhibitor (IC50 > 50 μmol/L) (Endo, 2004); actomyosin ATPase activator. Ref: J. Kobayashi, et al, Tetrahedron 1990, 46, 5579│ P. A. Keifer, et al, JOC, 1991, 56, 2965; 6728│ A. Vassas, et al, PM, 1996, 62, 28│ T. Endo, et al, JNP, 2004, 67, 1262

162

3 Pyrrole Indole and Imidazole Alkaloids

Br H 2N Br

N N H

HN

H N

10

O

Br

N H N

N H

NH2

H N H

O

455 (Z)-3-Bromohymenialdisine Type: Pyrrole-imidazole alkaloids. C11H9Br2N5O2 Source: Sponge Axinella carteri (Java, Indonesia). Pharm: Cytotoxic (mus in vitro, L5178Y, ED50 = 3.9 μg/mL). Ref: A. Supriyono, et al, Z. Naturforsch. C. Biosci., 1995, 50, 669 H2N N HN

O

Br

Z

Br N H

N H O

456 4-Bromopalauamine Type: Pyrrole-imidazole alkaloids. C17H21BrClN9O2 Amorph. tan solid, [α]D = −64.4° (c = 2.6, MeOH). Source: Sponge Stylotella aurantium (Palau Oceania). Pharm: Cytotoxic; immunosuppressant. Ref: Kinnel, R.B. et al, JOC, 1998, 63, 3281 Br 5 4

H N

N H 2N OH N H HN

12

H

N H 2N

Cl

O

N H

NH2

17 19

3.1 Pyrrole Alkaloids

163

457 3-Bromostyloguanidine Type: Pyrrole-imidazole alkaloids. C17H21BrClN9O2 Tan solid, [α]D = +57.5° (c = 0.7, MeOH). Source: Sponge Stylotella aurantium (Yap Sea, Australia). Pharm: Chitinase inhibitor; antifoulant (inhibits moulting of cyprid larvae of barnacles, 10 ppm). Ref: T. Kato, et al, Tet. Lett., 1995, 36, 2133│ R. B. Kinnel, et al, JOC, 1998, 63, 3281 Br

2

3

H

NH

N H 2N OH

N H

O

N H

HN

12

H

N H 2N

NH2

17

Cl

19

458 Carteramine A Type: Pyrrole-imidazole alkaloids. C22H21Br4ClN10O3 Light yellow powder, [α]D17 = −44° (c = 0.5, MeOH), [α]D23 = −42° (c = 1.26, MeOH). Source: Sponges Axinella verrucosa, Stylissa carteri and Stylissa caribica. Pharm: Anti-inflammatory (neutrophil chemotaxis inhibitor, IC50 = 5 μmol/L). Ref: H. Kobayashi, et al, Tet. Lett., 2007, 48, 2127 Br

Br

3

H

2

NH

N H 2N OH HN

N H

N

12

N H 2N

Cl

O

H

Br H H N N H

17 19

Br

O

459 12-Chloro-11-hydroxyldibromoisophakellin Type: Pyrrole-imidazole alkaloids. C11H10Br2ClN5O2 [α]D23 = +51° (c = 0.41, MeOH). Source: Sponge Axinella brevistyla (Japan waters). Pharm: Antifungal (inhibits growth of erg6 mutant of yeast Saccharomyces cerevisiae, 30 μg/disk); cytotoxic (L1210, IC50 = 2.5 μg/mL). Ref: S. Tsukamoto, et al, JNP, 2001, 64, 1576

164

3 Pyrrole Indole and Imidazole Alkaloids

Br

Br H

NH

N H 2N N H

N

O

HO Cl

460 Clathramide A Type: Pyrrole-imidazole alkaloids. C13H17BrN4O3 Amorph. solid, [α]D25 = −5° (c = 0.001, MeOH). Source: Sponge Agelas clathrodes (Caribbean, yield = 7.2% dw). Pharm: Antifungal (mixture with Clathramide B, 100 μg, Aspergillus niger, IZD = 8 mm). Ref: F. Cafieri, et al, Tetrahedron, 1996, 52, 13713│ F. Cafieri, et al, BoMCL, 1997, 7, 2283 Br

H N+

H N

N H

H

N

O

–

O

O

461 Clathramide B Type: Pyrrole-imidazole alkaloids. C13H17BrN4O3 Amorph. solid, [α]D25 = +11° (c = 0.001, MeOH). Source: Sponge Agelas clathrodes. Pharm: Antifungal (mixture with Clathramide A, 100 μg, Aspergillus niger, IZD = 8 mm). Ref: F. Cafieri, et al, Tetrahedron, 1996, 52, 13713│ F. Cafieri, et al, JNP, 1998, 61, 122 Br H N

N

8

12

N H

O

H O

N OH

462 Clathramide C Type: Pyrrole-imidazole alkaloids. C12H15BrN4O3 Amorph. solid, [α]D25 = −6°(c = 0.001, MeOH). Source: Sponge Agelas dispar (Caribbean Sea). Pharm: Antifungal (mixture with Clathramide D 100 μg, agar disk diffusion assay, Aspergillus niger, IZD = 7 mm). Ref: F. Cafieri, et al, Tetrahedron, 1996, 52, 13713│ F. Cafieri, et al, JNP, 1998, 61, 122

3.1 Pyrrole Alkaloids

165

Br H N

N

8

12

N N H

O

H

OH

O

463 Clathramide D Type: Pyrrole-imidazole alkaloids. C12H15BrN4O3 Source: Sponge Agelas dispar (Caribbean Sea). Pharm: Antifungal (mixture with Clathramide C 100 μg, agar disk diffusion assay, Aspergillus niger, IZD = 7 mm); serotonin receptor antagonist. Ref: F. Cafieri, et al, Tetrahedron, 1996, 52, 13713│ F. Cafieri, et al, JNP, 1998, 61, 122 Br H N

N

N

N H

O

H

12

8

O

OH

464 Clathrodine Type: Pyrrole-imidazole alkaloids. C11H13N5O Amorph. solid. Source: Sponge Agelas clathrodes. Pharm: Antibacterial (Proteus vulgaris, Staphylococcus aureus, Shigella flexneri, MIC = 1 mg/mL); cytotoxic (SW480, ED50 = 53 μg/mL, cell growth inhibitor). Ref: J. J. Morales et al, JNP, 1991, 54, 629 N NH2

H N

N H

N H

O

465 Cycloaplysinopsin C Type: Pyrrole-imidazole alkaloids. C28H28N8O3 Amorph. yellow solid, [α]D = +4° (c = 0.06, MeOH). Source: Stony coral Tubastraea sp. (Hanish Is., Yemen). Pharm: Antiplasmodial (CSPF F32/Tanzania, IC50 = 1.48 μg/mL; CRPF FcB1/Colombia, IC50 = 1.2 μg/mL). Ref: M. Meyer,et al., Nat. Prod. Res., 2009, 23, 178

N

O HO

NH 8

N

H N H O

3

N

N NH

N H

166

3 Pyrrole Indole and Imidazole Alkaloids

466 (Z)-Debromoaxinohydantoin Spongiacidin C Type: Pyrrole-imidazole alkaloids. C11H10N4O3 Amorph. solid, mp 213−218 °C (dec). Source: Sponges Stylotella aurantium, Axinella carteri, Hymeniacidon sp. (Okinawa) and Stylissa massa (Indonesia). Pharm: PKC Inhibitor (IC50 = 22.0 μmol/L); USP7 inhibitor (first USP7 inhibitor from a natural source, selective USP7 inhibitor, IC50 = (3.8 ± 1.8)μmol/L, a new lead as an oncological therapeutic) (Yamaguchi, 2013). Ref: A. D. Patil, et al, Nat. Prod. Lett., 1997, 9, 201│ K. Inaba, et al, JNP, 1998, 61, 693│ S. A. Basaif, et al, J. Saudi Chem. Soc., 2006, 9, 683│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev)│ M. Yamaguchi, et al, Bioorg. Med. Chem. Lett., 2013, 23, 3884 O

H N

HN

O Z

N H

N H O

467 (10Z)-Debromohymenialdisine Type: Pyrrole-imidazole alkaloids. C11H11N5O2 Cryst. + 2H2O (H2O), mp 220–225 °C (dec). Source: Sponges Acanthella aurantiaca (Red Sea), Axinella verrucosa, Axinella sp. (deep water, Great Australian Bight), Pseudaxinella sp. (Republic of Palau, 1979), Phakellia flabellate (Great Barrier Reef), Hymeniacidon aldis (Okinawa), Hymeniacidon spp., Axinella carteri, Stylotella aurantium (Palau, Oceania) and Stylissa flabelliformis, an unidentified sponge (Korolevu, Fiji). Pharm: PKC inhibitor (IC50 = 1.3 μmol/L); MAP kinase kinase MEK inhibitor (IC50 = 6.0 nmol/L); Polo-Like kinase-1 inhibitor (10 μmol/L); cytotoxic (P388, GI50 = 5.0 μg/mL); insecticide; anti-inflammatory. Ref: G. Cimino, et al, Tet. Lett., 1982, 23, 767│ C. A. Mattia, et al, Acta Crystallorg. Sect. B, 1982, 38, 2513│ I. Kitagawa, et al, CPB, 1983, 31, 2321│ H. Annoura, et al, Tet. Lett., 1995, 36, 413│ D. H. Williams, et al, Nat. Prod. Lett., 1996, 9, 57│ A. D. Patil, et al, Nat. Prod. Lett., 1997, 9, 201│ D. Tasdemir, et al, J. Med. Chem. 2002, 45, 529│ G. R. Pettit, et al, JNP, 2008, 71, 438│ P. Sauleau,; et al, Tet. Lett., 2011, 52, 2676│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev)│ H. Zhang, et al, Tet. Lett., 2012, 53, 3784

3.1 Pyrrole Alkaloids

H N

H 2N

167

O

N

Z

3

N H

N H O

468 Debromooxysceptrine Type: Pyrrole-imidazole alkaloids. C22H25BrN10O3 [α]D25 = −25° (c = 0.108, MeOH) (di–Ac). Source: Sponges Agelas conifera, Agelas clathrodes and Agelas mauritiana. Pharm: Antiviral; antibacterial. Ref: J. Kobayashi, et al, Experientia, 1991, 47, 301│ P. A. Keifer, et al, JOC, 1991, 56, 2965 NH2 O N N H

N H

H

NH

N N H

O

H

H N

Br

NH

O NH2

469 Debromosceptrine Type: Pyrrole-imidazole alkaloids. C22H24BrN10O2 [α]D25 = −30° (c = 1.03, MeOH) (di– Ac). Source: Sponges Agelas nakamurai (with two CF3COO−, yield = 0.024% ww, Ambon, Indonesia, 1997) and Agelas conifera. Pharm: Antibacterial (0.2 μmol/disk: Bacillus subtilis 168, IZD = 10 mm). Ref: C. Eder, et al, JNP, 1999, 62, 1295│ P. A. Keifer, et al, JOC, 1991, 56, 2965; 6728│ X. Shen, et al, JNP, 1998, 61, 1302 Br

NH2

O N N H

N H

H H

H N HN N H

NH

N

O NH2

168

3 Pyrrole Indole and Imidazole Alkaloids

470 Dibromoagelaspongin Type: Pyrrole-imidazole alkaloids. C11H11Br2N5O2 Yellow–green cryst. (MeOH/ Me2CO) (hydrochloride), mp 233–235 °C (dec) (hydrochloride). Source: Sponge Agelas sp. Pharm: Glucanase inhibitor. Ref: S. A. Fedoreyev, et al, Tetrahedron, 1989, 45, 3487

OH N

O

N N N H 11

Br

NH2

10

Br

471 2,2'-Dibromoageliferin Type: Pyrrole-imidazole alkaloids. C22H22Br4N10O2 [α]D33 = +3° (c = 0.1, MeOH). Source: Sponges Agelas sp. SS-1003 (off Seragaki, Okinawa), Agelas conifera, Agelas cf. mauritiana and Astrosclera willeyana. Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 2.08 μg/mL; Bacillus subtilis, MIC = 4.16 μg/mL; gram-negative bacterium Escherichia coli, MIC = 16.7 μg/mL) (Endo, 2004); protein phosphatase 2A inhibitor (IC50 > 50 μmol/L) (Endo, 2004); actomyosin ATPase activator. Ref: J. Kobayashi, et al, Tetrahedron, 1990, 46, 5579│ P. A. Keifer, et al, JOC, 1991, 56, 2965; 6728│ A. Vassas, et al, PM, 1996, 62, 28│ T. Endo, et al, JNP, 2004, 67, 1262 Br H2 N Br

N N H

H N

H

O

Br

10

H N Br

HN

N H

N NH2 N H

O

472 4,5-Dibromopalauamine Type: Pyrrole-imidazole alkaloids. C17H20Br2ClN9O2 Solid, [α]D = −115.3° (c = 2.7, MeOH). Source: Sponges Stylotella aurantium and Stylissa flabellata. Pharm: Cytotoxic (hmn melanoma, IC50 = 0.25 μg/mL). Ref: R. B. Kinnel, et al, JOC, 1998, 63, 3281│ U. M. Reinscheid, et al, EurJOC, 2010, 6900

3.1 Pyrrole Alkaloids

169

Br

Br

5 4

H N

N H 2N N OH H

N

O

H HN

12

H

N H 2N

NH2

17

Cl

19

473 Dibromophakellstatin Type: Pyrrole-imidazole alkaloids. C11H10Br2N4O2 Cryst. (toluene/MeOH), mp 245 °C (dec). Source: Sponge Phakellia mauritiana (Seychelles). Pharm: Cytotoxic (OVCAR-3, ED50 = 15.7 μg/mL, SF295, ED50 = 18.8 μg/mL, A498, ED50 = 17.8 μg/mL, H460, ED50 = 22.0 μg/mL, KM20L2, ED50 = 20.1 μg/mL, SK-MEL-5, ED50 = 17.0 μg/mL). Ref: G. R. Pettit, et al, JNP, 1997, 60, 180 Br

Br H

H N

N

O N H

O

N

474 Dibromosceptrine Type: Pyrrole-imidazole alkaloids. C22H22Br4N10O2 [α]D25 = −44° (c = 1.03, MeOH) (di–Ac). Source: Sponges Agelas conifera and Agelas clathrodes. Pharm: Antifoulant; neutrotoxin. Ref: P. A. Keifer, et al, JOC, 1991, 56, 2965; 6728 Br

3

O

N NH

N H

Br

Br

Br

3'

N H

N H

N H H

H N

H

O

N N H

NH2

475 2,3-Dibromostyloguanidine Type: Pyrrole-imidazole alkaloids. C17H20Br2ClN9O2 Off–white cryst. (2–propanol/ MeOH), [α]D = −70.8° (c = 0.6, MeOH). Source: Sponge Stylotella aurantium. Pharm: Chitinase inhibitor; antifoulant. Ref: R. B. Kinnel, et al, JOC, 1998, 63, 3281

170

3 Pyrrole Indole and Imidazole Alkaloids

Br

Br

3

2

H

NH

N H2N OH

N H

HN

N

O

H 12

H

N

NH2

17

H 2N

Cl

19

476 Dictazole A Type: Pyrrole-imidazole alkaloids. C26H24BrN8O21+ Colorless powder, [α]D22 = +8.5° (c = 0.2, MeOH). Source: Sponge Smenospongia cerebriformis (Panama). Pharm: Aspartic protease BACE1 inhibitor (inhibited BACE1-mediated cleavage of amyloid precursor protein (APP) in a dose-dependent manner, IC50 = 50 μg/mL; BACE1 is widely believed to be a central role in pathology of Alzheimer’s disease). Ref: J. Dai, et al, JOC, 2010, 75, 2399 NH2

Br N

NH H

O HN

NH

H O

N N N

+

H

H

477 9,10-Dihydrokeramadine Type: Pyrrole-imidazole alkaloids. C12H16BrN5O Amorph. solid. Source: Sponge Agelas sp. SS-1003 (yield = 0.00018% ww, off Seragaki, Okinawa). Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC > 33.3 μg/mL; Bacillus subtilis, MIC > 33.3 μg/mL; gram-negative bacterium Escherichia coli, MIC > 33.3 μg/mL); protein phosphatase 2A inhibitor (IC50 > 50 μmol/L). Ref: T. Endo, et al, JNP, 2004, 67, 1262 Br H N

N H O

9

10

N NH2 N

3.1 Pyrrole Alkaloids

171

478 Dispacamide A Type: Pyrrole-imidazole alkaloids. C11H11Br2N5O2 Amorph. solid. Source: Sponges Agelas conifera (Caribbean, yield = 0.8% dw), Agelas dispar (Caribbean, yield = 3.5% dw), Agelas clathrodes (Caribbean, yield = 3.2% dw) and Agelas longissima (Caribbean, yield = 1.1% dw). Pharm: Antihistaminic (guinea pig ileum, apparent affinity of antagonistic effect pD2 = 5.52 ± 0.11, remarkable, spesific reversible noncompapetitive effect). Ref: Van Rossum, J. Arch. Int. Pharmacodyn. Ther., 1963, 143, 299 (pD2 definition)│ F. Cafieri, et al, Tet. Lett., 1996, 37, 3587│ F. Cafieri, et al, BoMCL, 1997, 7, 2283 NH2

Br HN Br

2

N

H N

N H

O

O

479 Dispacamide B 2-Debromodispacamide A Type: Pyrrole-imidazole alkaloids. C11H12BrN5O2 Source: Sponges Agelas conifera (Caribbean, yield = 3.5% dw), Agelas dispar (Caribbean, yield = 0.2% dw), Agelas clathrodes (Caribbean, yield = 0.5% dw) and Agelas longissima (Caribbean, yield = 3.3% dw). Pharm: Antihistaminic (guinea pig ileum, apparent affinity of antagonistic effect pD2 = 5.33 ± 0.08, remarkable, spesific reversible non-compapetitive effect). Ref: F. Cafieri, et al, Tet. Lett., 1996, 37, 3587│ F. Cafieri, et al, BoMCL, 1997, 7, 2283 NH2

Br HN 2

H N N H O

N O

480 Dispacamide C Type: Pyrrole-imidazole alkaloids. C11H11Br2N5O3 Source: Sponges Agelas conifera (Caribbean, yield = 0.8% dw), Agelas dispar (Caribbean, yield = 3.5% dw), Agelas clathrodes (Caribbean, yield = 3.2% dw) and Agelas longissima (Caribbean, yield = 1.1% dw). Pharm: Antihistaminic (guinea pig ileum, apparent affinity of antagonistic effect pD2 = 4.48 ± 0.05, mild, reversible non-compapetitive effect). Ref: F. Cafieri, et al, Tet. Lett., 1996, 37, 3587│ F. Cafieri, et al, BoMCL, 1997, 7, 2283

172

3 Pyrrole Indole and Imidazole Alkaloids

NH2

Br OH Br

2

HN

H N N H

N O

O

481 Dispacamide D Mukanadine A Type: Pyrrole-imidazole alkaloids. C11H12BrN5O3 Source: Sponges Agelas conifera (Caribbean, yield = 3.5% dw), Agelas dispar (Caribbean, yield = 0.2% dw), Agelas clathrodes (Caribbean, yield = 0.5% dw) and Agelas longissima (Caribbean, yield = 3.3% dw), Agelas nakamurai (Okinawa) and Axinella verrucosa. Pharm: Antihistaminic (guinea pig ileum, apparent affinity of antagonistic effect pD2 = 4.34 ± 0.10, mild, reversible non-compapetitive effect). Ref: F. Cafieri, et al, BoMCL, 1997, 7, 2283│ H. Uemoto, et al, JNP, 1999, 62, 1581│ M. Tsuda, et al, Tet. Lett., 1999, 40, 5709│ H. Uemoto, et al, JNP, 2000, 63, 1050 NH2

Br OH 2

HN

H N N H

O

N O

482 (10Z)-Hymenialdisine Type: Pyrrole-imidazole alkaloids. C11H10BrN5O2 Yellow needles + 1MeOH (MeOH aq) or yellow amorph. solid, mp 160–164 °C (dec). Source: Sponges Hymeniacidon aldis (Okinawa), Acanthella aurantiaca (Red Sea), Stylotella aurantium, Stylissa massa, Axinella verrucosa, Axinella carteri and Cymbastela cantharella. Pharm: PKC inhibitor (IC50 = 0.8 μmol/L); MAP kinase kinase MEK inhibitor (IC50 = 3.0 nmol/L); Polo-Like kinase-1 inhibitor (10 μmol/L); cyclin dependent Kinases CDK inhibitor (CDK1/cyclin B, IC50 = 22 nmol/L; CDK2/cyclin A, IC50 = 70 nmol/L; CDK2/cyclin E, IC50 = 40 nmol/L; CDK5/p25, IC50 = 28 nmol/L; glycogen synthase kinase 3 GSK-3, IC50 = 10 nmol/L; creatine kinase 1 CK1, IC50 = 35 nmol/L; possessing good selectivity); cytotoxic (P388); insecticide; Inhibits interleukin-1 stimulated rheumatoid synovial fibroblasts; anti-inflammatory. Ref: I. Kitagawa, et al, CPB1983, 31, 2321│ F. J. Schmitz, et al, JNP, 1985, 48, 47│ N. K. Utkina, et al, Khim. Prir. Soedin., 1985, 21, 578│ A. D. Patil, et al, Nat. Prod. Lett., 1997, 9, 201│ L. Meijer, et al, Chem. Biol. 2000, 7, 51│ D. Tasdemir, et al, J. Med. Chem. 2002, 45, 529│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev)│ P. Sauleau, et al, Tet. Lett., 2011, 52, 2676│ CRC Press, DNP on DVD, 2012, version 20.2

3.1 Pyrrole Alkaloids

N

H 2N

173

O

N H

Z

3

Br N H

N H O

483 Hymenidine Type: Pyrrole-imidazole alkaloids. C11H12BrN5O Amorph. solid. Source: Sponges Axinella sp. (deep water, Great Australian Bight), Hymeniacidon sp., Prosuberites laughlini (Aguadilla, Puerto Rico), and Agelas clathrodes. Pharm: Antibacterial (Staphylococcus aureus ATCC 25923, IC50 = 0.23 μmol/L, Staphylococcus aureus ATCC 9144, IC50 = 0.70 μmol/L, Bacillus subtilis ATCC 6051, IC50 = 0.55 μmol/L, Bacillus subtilis ATCC 6633, IC50 = 0.23 μmol/L, Escherichia coli ATCC 11775, IC50 = 1.1 μmol/L, Pseudomonas aeruginosa ATCC 10145, IC50 = 0.78 μmol/L); antituberculosis (inhibits growth of Mycobacterium tuberculosis H37Rv, MIC = 6.1 μg/mL); antifungal (Candida albicans ATCC 90028, IC50 = 0.79 μmol/L); IL-8 Rα receptor inhibitor (IC50 = 84 μmol/L); IL-8 Rβ receptor inhibitor (IC50 = 23.6 μmol/L); PKC inhibitor (IC50 = 20.9 μmol/L); antihypertensive; antimuscarinic; smooth muscle contractant; serotonin receptor antagonist. Ref: J. Kobayashi, et al, Experientia, 1986, 42, 1176│ J. Vicente, et al, Tet. Lett., 2009, 50, 4571│ H. Zhang, et al, Tet. Lett., 2012, 53, 3784 Br

O N H

N H 2N

1

2

N H

N H

484 (–)-Hymenine‡ 4ξ,5-Dihydroodiline Type: Pyrrole-imidazole alkaloids. C11H11Br2N5O Source: Sponge Hymeniacidon sp. Pharm: IL-8 Rα receptor inhibitor (IC50 = 61 μmol/L); IL-8 Rβ receptor inhibitor (IC50 = 37.1 μmol/L); Protein kinase C inhibitor (IC50 = 30.6 μmol/L); α-Adrenoceptor blocker (potent). Ref: J. Kobayashi, et al, Experientia, 1986, 42, 1064│ Y. Xu, et al, Tet. Lett., 1994, 35, 351

174

3 Pyrrole Indole and Imidazole Alkaloids

H 2N

N HN

Br

Br N H

N H O

485 Keramadine Type: Pyrrole-imidazole alkaloids. C12H14BrN5O Powder, mp 183–187 °C. Source: Sponges Agelas sp. (Okinawa) and Agelas dispar (Caribbean Sea). Pharm: Antibacterial (Mueller-Hinton agar test, gram-positive bacteria: Bacillus subtilis ATCC 6633, MIC = 40 μg/mL; Staphylococcus aureus ATCC6538, MIC = 35 μg/mL) (Cafieri, 1998); IL-8 Rα receptor inhibitor (IC50 = 98 μmol/L); IL-8 Rβ receptor inhibitor (IC50 = 10.8 μmol/L); PKC inhibitor (IC50 = 26 μmol/L). Ref: H. Nakamura, et al, Tetrahedron, Lett., 1984, 25, 2475│ T. Lindel et al, Tet. Lett., 1998, 39, 2541│ F. Cafieri, et al, JNP, 1998, 61, 122 Br H N N H O N N NH2

486 Konbuacidin A Type: Pyrrole-imidazole alkaloids. C22H22Br3ClN10O3 Amorph. solid, [α]D24 = −45° (c = 0.5, MeOH). Source: Sponge Hymeniacidon sp. (Okinawa). Pharm: IL-8 Rα receptor inhibitor (IC50 = 3.4 μmol/L); IL-8 Rβ receptor inhibitor (IC50 = 3.2 μmol/L); Protein kinase C inhibitor (C50 = 1.8 μmol/L); CDK4 inhibitor (IC50 = 20 μg/mL). Ref: J. Kobayashi, et al, Tetrahedron, 1997, 53, 15681│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev)

3.1 Pyrrole Alkaloids

175

Br

5

4

H N

N H 2N OH N H HN

12

H

N H 2N

O

N H

Br H N

17

Cl

19

Br

N H

O

487 Mauritamide A Type: Pyrrole-imidazole alkaloids. C15H22Br2N6O5S Amorph. solid, [α]D20 = +1.3° (c = 0.003, MeOH). Source: Sponges Agelas mauritiana (Fiji) and Agelas sp. Pharm: Protein tyrosine kinase inhibitor. Ref: C. Jiménez, et al, Tet. Lett., 1994, 35, 1375 O

Br

H N

H N

Br

N

HN O

NH

N H

O O

S O

488 Mauritiamine Type: Pyrrole-imidazole alkaloids. C22H20Br4N10O3 Solid. Source: Sponges Agelas sp. SS-1003 (off Seragaki, Okinawa) and Agelas mauritiana. Pharm: Antifoulant; antibacterial (moderate). Ref: S. Tsukamoto, et al, JNP, 1996, 59, 501│ T. Endo, et al, JNP, 2004, 67, 1262 Br

O H N

2

Br

N H Br

O

N H O

NH2 N H N

H N

2'

Br

N

NH2 N H

176

3 Pyrrole Indole and Imidazole Alkaloids

489 3-O-Methylmassadine chloride Type: Pyrrole-imidazole alkaloids. C25H27Br4ClN8O52+ White solid, [α]D21 = −19.7° (c = 0.08, MeOH). Source: Sponge Axinella sp. (deep water, Great Australian Bight). Pharm: Antibacterial (sub μmol/L); antibacterial (Staphylococcus aureus ATCC 25923, IC50 = 4.2 μmol/L, Staphylococcus aureus ATCC 9144, IC50 = 3.7 μmol/L, Bacillus subtilis ATCC 6051, IC50 = 2.6 μmol/L, Bacillus subtilis ATCC 6633, IC50 = 2.2 μmol/L, Escherichia coli ATCC 11775, IC50 = 4.4 μmol/L, Pseudomonas aeruginosa ATCC 10145, IC50 = 4.9 μmol/L). Ref: H. Zhang, et al, Tet. Lett., 2012, 53, 3784 H N

Br

NH2+

O HN N H

Br

NH

O H

O N H

H N

O

N

O H

Cl

NH NH2+

Br Br

490 Monobromoisophakellin Type: Pyrrole-imidazole alkaloids. C11H12BrN5O Source: Sponges Prosuberites laughlini (Aguadilla, Puerto Rico) and Agelas sp. Pharm: Antituberculosis (inhibits growth of Mycobacterium tuberculosis H37Rv, MIC = 64.0 μg/mL). Ref: M. Assmann, et al, Z. Naturforsch., C, 2002, 57, 153│ J. Vicente, et al, Tet. Lett., 2009, 50, 4571 Br 2

H

H N

NH

H2N N

N

O

11 12

491 Mukanadine F Type: Pyrrole-imidazole alkaloids. C11H10Br2N4O4 Amorph. solid, [α]D20 = −3.9° (c = 0.3, MeOH). Source: Sponge Agelas sp. (several collections, Okinawa). Pharm: Antifungal (Aspergillus niger, MIC = 16.7 μg/mL). Ref: T. Yasuda, et al, JNP, 2009, 72, 488

3.1 Pyrrole Alkaloids

177

O Br OH

HN

NH

H N

Br

N H

9R

O

O

492 Nagelamide A Type: Pyrrole-imidazole alkaloids. C22H22Br4N10O2 Amorph. solid. Source: Sponge Agelas sp. SS-1003 (yield = 0.00077% ww, off Seragaki, Okinawa). Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 2.08 μg/mL; Bacillus subtilis, MIC = 16.7 μg/mL; gram-negative bacterium Escherichia coli, MIC = 33.3 μg/mL); protein phosphatase 2A inhibitor (IC50 = 48 μmol/L). Ref: T. Endo, et al, JNP, 2004, 67, 1262 Br O N

Br

N H

N H

H

Br

NH2

N H N

9

H N

Br

N H

9' 10'

O

NH2

N H

493 Nagelamide B Type: Pyrrole-imidazole alkaloids. C22H22Br4N10O3 Amorph. solid. Source: Sponge Agelas sp. SS-1003 (yield = 0.00021% ww, off Seragaki, Okinawa). Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 4.17 μg/mL; Bacillus subtilis, MIC = 33.3 μg/mL; gram-negative bacterium Escherichia coli, MIC = 33.3 μg/mL); protein phosphatase 2A inhibitor (IC50 > 50 μmol/L). Ref: T. Endo, et al, JNP, 2004, 67, 1262 Br O N

Br

N H

H

N H

Br HO Br

H N N H

9' 10'

O

N H

9

NH2

N N H

NH2

178

3 Pyrrole Indole and Imidazole Alkaloids

494 Nagelamide C Type: Pyrrole-imidazole alkaloids. C22H20Br4N10O2 Amorph. solid. Source: Sponge Agelas sp. SS-1003 (yield = 0.00032% ww, off Seragaki, Okinawa). Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 4.17 μg/mL; Bacillus subtilis, MIC = 33.3 μg/mL; gram-negative bacterium Escherichia coli, MIC = 33.3 μg/mL); protein phosphatase 2A inhibitor (IC50 > 50 μmol/L). Ref: T. Endo, et al, JNP, 2004, 67, 1262 Br O N

Br

N H

N H

9

NH2

N H N

Br H N

Br

9'

N H

10'

O

NH2

N H

495 Nagelamide D Type: Pyrrole-imidazole alkaloids. C22H24Br4N10O2 Amorph. solid. Source: Sponge Agelas sp. SS-1003 (yield = 0.00013% ww, off Seragaki, Okinawa). Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 4.17 μg/mL; Bacillus subtilis, MIC = 33.3 μg/mL; gram-negative bacterium Escherichia coli, MIC = 33.3 μg/mL). Ref: T. Endo, et al, JNP, 2004, 67, 1262│ M. R. Bhandari, et al, Org. Lett., 2009, 11, 1535 Br O N

Br

N H

N H

H

Br

N H

9

NH2

N Br

H N

N H

9' 10'

N H

NH2

O

496 Nagelamide E Type: Pyrrole-imidazole alkaloids. C22H24Br2N10O2 Amorph. solid, [α]D17 = −11.3° (c = 1, MeOH). Source: Sponge Agelas sp. SS-1003 (yield = 0.00062% ww, off Seragaki, Okinawa). Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 4.17 μg/mL; Bacillus subtilis, MIC = 16.7 μg/mL; gram-negative bacterium Escherichia coli, MIC = 33.3 μg/mL). Ref: T. Endo, et al, JNP, 2004, 67, 1262

3.1 Pyrrole Alkaloids

179

Br H2N N N H

H N

HN H N

O

Br

10

NH2

H N N H

N H

O

497 Nagelamide F Type: Pyrrole-imidazole alkaloids. C22H23Br3N10O2 Amorph. solid, [α]D17 = −14.1° (c = 1, CHCl3). Source: Sponge Agelas sp. SS-1003 (yield = 0.00077% ww, off Seragaki, Okinawa). Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 4.17 μg/mL; Bacillus subtilis, MIC = 16.7 μg/mL; gram-negative bacterium Escherichia coli, MIC = 33.3 μg/mL). Ref: T. Endo, et al, JNP, 2004, 67, 1262 Br H2 N Br

N N H

H N

10

H N N H

H N

O

Br

HN

NH2 N H

O

498 Nagelamide G Type: Pyrrole-imidazole alkaloids. C22H22Br4N10O2 Amorph. solid, [α]D17 = +6.7° (c = 1, MeOH). Source: Sponge Agelas sp. SS-1003 (yield = 0.00041% ww, off Seragaki, Okinawa). Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 2.08 μg/mL; Bacillus subtilis, MIC = 16.7 μg/mL; gram-negative bacterium Escherichia coli, MIC = 33.3 μg/mL); protein phosphatase 2A inhibitor (IC50 = 13 μmol/L). Ref: T. Endo, et al, JNP, 2004, 67, 1262

180

3 Pyrrole Indole and Imidazole Alkaloids

Br H 2N Br

N N H

H N

HN H N

O

Br

10

NH2

H N Br

N H

N H

O

499 Nagelamide H Type: Pyrrole-imidazole alkaloids. C24H25Br4N11O5S Amorph. solid. Source: Sponge Agelas sp. SS-1003 (yield = 0.00032% ww, off Seragaki, Okinawa). Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 16.7 μg/mL; Bacillus subtilis, MIC = 33.3 μg/mL; gram-negative bacterium Escherichia coli, MIC > 33.3 μg/mL); protein phosphatase 2A inhibitor (IC50 = 46 μmol/L). Ref: T. Endo, et al, JNP, 2004, 67, 1262 O S OH O

N

Br

N H N

Br

N H

Br

NH2

N H

O

N Br

H N

N H

NH2

N H

O

500 Nagelamide O Type: Pyrrole-imidazole alkaloids. C22H24Br3ClN10O4 Amorph. solid, [α]D22 = +1.6° (c = 0.75, MeOH). Source: Sponge Agelas sp. (several collections, Okinawa). Pharm: Antibacterial (Bacillus subtilis, Micrococcus luteus and Staphylococcus aureus, all MICs = 33.3 μg/mL). Ref: T. Yasuda, et al, JNP, 2009, 72, 488 HO

O

Cl

H N

N H

1

HN

N H

H 5

9

HN

OH NH

Br O N H

2''

N H

Br

HN 2'

NH

Br

3.1 Pyrrole Alkaloids

181

501 Nagelamide W Type: Pyrrole-imidazole alkaloids. C12H16Br2N8O2+ Colorless amorphous solid, [α]D21 = −1.2° (c = 0.25, MeOH). Source: Sponge Agelas sp. (Kerama I., Okinawa). Pharm: Antifungal (Candida albicans, IC50 = 4 μg/mL). Ref: N. Tanaka, et al, Tet. Lett., 2013, 54, 3794 H N

Br HN N H

H

NH

H N

Br

+

O

NH N H

N

+

H

H

502 Nagelamide X Type: Pyrrole-imidazole alkaloids. C24H28Br4N11O6S1+ Colorless amorphous solid, [α]D21 ≈ 0° (c = 0.25, MeOH). Source: Sponge Agelas sp. (Kerama I., Okinawa). Pharm: Antibacterial (Escherichia coli, MIC > 32 μg/mL, Staphylococcus aureus, MIC = 8.0 μg/mL, Bacillus subtilis, MIC > 32 μg/mL, Micrococcus luteus, MIC = 8.0 μg/mL); antifungal (Aspergillus niger, IC50 = 32 μg/mL, Trichophyton mentagrophytes, IC50 = 16 μg/mL, Candida albicans, IC50 = 2.0 μg/mL, Cryptococcus neoformans, IC50 > 32 μg/mL). Ref: N. Tanaka, et al, Org. Lett., 2013, 15, 3262 Br

Br

O N H

N H

H N

H N

H +

N

H

HN

N H

N H

N

+

H OH

H

NH O

S

O –

O

O

Br N H Br

503 Nagelamide Y Type: Pyrrole-imidazole alkaloids. C24H28Br4N11O5S1+ Colorless amorphous solid, [α]D22 ≈ 0° (c = 0.25, MeOH). Source: Sponge Agelas sp. (Kerama I., Okinawa). Pharm: Antibacterial (Escherichia coli, MIC > 32 μg/mL, Staphylococcus aureus, MIC > 32 μg/mL,

182

3 Pyrrole Indole and Imidazole Alkaloids

Bacillus subtilis, MIC > 32 μg/mL, Micrococcus luteus, MIC > 32 μg/mL); antifungal (Aspergillus niger, IC50 > 32 μg/mL, Trichophyton mentagrophytes, IC50 > 32 μg/mL, Candida albicans, IC50 = 2.0 μg/mL, Cryptococcus neoformans, IC50 > 32 μg/mL). Ref: N. Tanaka, et al, Org. Lett., 2013, 15, 3262 Br

Br

O N H

N H

H N

H N

H N

H

HN

N H

N H

+

N

+

H

H NH

O

S O

O –

O

Br N H Br

504 Nakamuric acid Type: Pyrrole-imidazole alkaloids. C20H21Br2N7O4 Amorph. brown solid, [α]D = −9.9° (c = 0.26, MeOH). Source: Sponge Agelas nakamurai (yield = 0.0005% ww, Ambon, Indonesia, 1997). Pharm: Antibacterial (0.2 μmol/disk: Bacillus subtilis 168, IZD = 9 mm). Ref: C. Eder, et al, JNP, 1999, 62, 1295 Br

O

N NH2

N H

N H

N H

Br

H

H

H N

OH O

N H

O

505 Nakamuric acid methyl ester Type: Pyrrole-imidazole alkaloids. C21H23Br2N7O4 Amorph. brown solid, [α]D = −4.1° (c = 0.30, MeOH). Source: Sponge Agelas nakamurai (yield = 0.0013% ww, Ambon, Indonesia, 1997). Pharm: Antibacterial (0.2 μmol/disk: Bacillus subtilis 168, IZD = 9 mm). Ref: C. Eder, et al, JNP, 1999, 62, 1295

3.1 Pyrrole Alkaloids

Br

O

183

N NH2

N H

N H

N H

H N

Br

H

H O O

N H

O

506 (E)-Oroidin Type: Pyrrole-imidazole alkaloids. C11H11Br2N5O Noncryst. Source: Sponges Agelas conifera (Caribbean, yield = 2.1% dw), Agelas dispar (Caribbean, yield = 4.2% dw), Agelas clathrodes (Caribbean, yield = 2.1% dw) and Agelas longissima (Caribbean, yield = 4.1% dw), Agelas sp. SS-1003 (off Seragaki, Okinawa), Agelas oroides, Agelas conifera, Agelas longissima, Agelas mauritiana, Agelas clathrodes, Agelas wiedenmayeri, Agelas sceptrum, Axinella verrucosa, Axinella damicornis, Hymeniacidon sp., Pseudaxinyssa cantharella, Acanthella carteri and Acanthella aurantiaca. Pharm: Antibacterial (gram-positive bacteria: Micrococcus luteus, MIC = 4.07 μg/mL; Bacillus subtilis, MIC = 8.33 μg/mL; gram-negative bacterium Escherichia coli, MIC = 33.3 μg/mL) (Endo, 2004); antibacterial (Staphylococcus aureus ATCC 25923, IC50 = 0.96 μmol/L, Staphylococcus aureus ATCC 9144, IC50 = 1.2 μmol/L, Bacillus subtilis ATCC 6051, IC50 = 2.0 μmol/L, Bacillus subtilis ATCC 6633, IC50 = 0.62 μmol/L, Escherichia coli ATCC 11775, IC50 = 0.55 μmol/L, Pseudomonas aeruginosa ATCC 10145, IC50 = 1.4 μmol/L); antifungal (Candida albicans ATCC 90028, IC50 = 6.3 μmol/L); protein phosphatase 2A inhibitor (IC50 = 50 μmol/L) (Endo, 2004); antibacterial (gram-positive and gram-negative bacteria, MIC ≈ 60 μg/mL, moderate) (Cafieri, 1995); adrenergic antagonist; serotonin antagonist; antimuscarinic; antifoulant; antihistaminic (guinea pig ileum, apparent affinity of antagonistic effect pD2 = 4.02 ± 0.11, non-spesific non-compapetitive effect); IL-8 Rα receptor inhibitor (IC50 = 9.6 μmol/L); IL-8 Rβ receptor inhibitor (IC50 = 10.8 μmol/ L); protein kinase C inhibitor (IC50 = 4.8 μmol/L);antimalarial (Plasmodium falciparum K1 strain, IC50 = 3.9–7.9 μg/mL, MMOA: FabI inhibition). Ref: S. Forenza, et al, E. J. Chem. Soc.,Chem. Commun. 1971, 1129│ E. E. Gracia,et al, J. Chem. Soc., Chem. Commun. 1973, 78│ R. P. Walker, et al, JACS, 1981, 103, 6772│ D. J. Faulkner, Natural Product Reports, 1984, 552│ J. J. Morales, et al, JNP, 1991, 54, 629│ F. Cafieri, et al, Tet. Lett., 1995, 36, 7893│ F. Cafieri, et al, BoMCL, 1997, 7, 2283│ G. M. Koenig, et al, PM, 1998, 64, 443│ T. Endo, et al, JNP, 2004, 67, 1262│ D. Tasdemir, et al, BoMC 2007, 15, 6834│ H. Zhang, et al, Tet. Lett., 2012, 53, 3784

184

3 Pyrrole Indole and Imidazole Alkaloids

Br

O

H 2N

1

N H

N

N H

Br

N H

507 Oxysceptrine Oxysceptrin Type: Pyrrole-imidazole alkaloids. C22H24Br2N10O3 Amorph. solid, [α]D = −19.7° (c = 1.02, MeOH). Source: Sponges Agelas cf. nemoechinata, Agelas clathrodes, Agelas mauritiana and Agelas conifera. Pharm: Actomyosin ATPase activator; antiviral; antibacterial; antifoulant. Ref: J. Kobayashi, et al, Experientia, 1991, 47, 301│ P. A. Keifer, et al, JOC, 1991, 56, 2965 NH2

Br

O N N H

NH

N H O H

H N

Br

N N H

NH

O NH2

508 Palauamine Palau’amine Type: Pyrrole-imidazole alkaloids. C17H22ClN9O2 Off–white amorph. powder, [α]D24 = −45.2° (c = 3.0, MeOH). Source: Sponges Stylotella aurantium and Stylotella agminata (Western Caroline I., Palau, Oceania). Pharm: Cytotoxic (P388, IC50 = 0.1 μg/mL; A549, IC50 = 0.2 μg/mL; murine lymphocytes, 1.5 μg/mL effective); immunosuppressive (mixed lymphocyte reaction, IC50 < 18 ng/mL); antibiotic (Penicillium notatum, 50 μg/disk, IZD = 24 mm); antifungal; acute toxicity (low); LD50 (ip, mice) = 13 mg/kg. Ref: R. B. Kinnel, et al, JACS, 1993, 115, 3376│ R. B. Kinnel, et al, JOC, 1998, 63, 3281│ M. S. Buchanan, et al, Tet. Lett., 2007, 48, 4573 5

4

H N

N H 2N OH N H HN

N

12

H

N H 2N

Cl

O

H

NH2

17 19

3.1 Pyrrole Alkaloids

185

509 Sceptrine Type: Pyrrole-imidazole alkaloids. C22H24Br2N10O2 Cryst. + H2O (H2O) (hydrochloride), mp 215–225 °C (dec) (hydrochloride), [α]D = −7.4° (c = 1.2, MeOH). Source: Sponges Agelas nakamurai (with two CF3COO−, yield = 0.24% ww, Ambon, Indonesia, 1997), Agelas sceptrum, Agelas conifera, Agelas schmidtii, Agelas dispar, Agelas nakamurai, Agelas novaecaledoniae, Agelas longissima, Agelas clathrodes, Axinella sp. and Hymeniacidon sp. Pharm: Antibacterial (Streptococcus faecalis, MIC = 0.008 μg/mL; Bacillus subtilis 6633ATCC, MIC = 0.012 μg/mL; Staphylococcus aureus 6538ATCC, MIC = 0.030 μg/mL; Bacillus cereus 213PCl, MIC = 0.040 μg/mL; Escherichia coli, MIC > 0.060 μg/mL; Salmonella typhi 1943OATCC, MIC > 0.060 μg/mL; Pseudomonas aeruginosa, MIC > 0.060 μg/mL) (Cafieri, 1995); antibacterial (0.2 μmol/disk: Bacillus subtilis 168, IZD = 16 mm; Staphylococcus aureus ATCC 25923, IZD = 16 mm; Escherichia coli ATCC 25922, IZD = 9 mm; Escherichia coli HB101, IZD = 13 mm) (Eder, 1999); antiserotonergic, prophage induction; ichthyotoxic; adrenergic antagonist; serotonin antagonist; anti-muscarinic; somatostatin inhibitor; vasoactive intestinal peptide inhibitor; antihistamine. Ref: R. P. Walker, et al, JACS, 1981, 103, 6772│ K. F. Albizati, et al, JOC, 1985, 50, 4163│ F. Cafieri, et al, Tet. Lett., 1995, 36, 7893│ C. Eder, et al, JNP, 1999, 62, 1295│ A. Cipres, et al, ACS Chem. Biol., 2010, 5, 195 Br

3

O

N NH2

N H Br

3'

N H

N H

N H H

H N

H N N H

O

NH2

510 Slagenine A Type: Pyrrole-imidazole alkaloids. C11H13BrN4O4 Amorph. solid, [α]D27 = +11°(c = 1.2, MeOH). Source: Sponge Agelas nakamurai (yield = 0.0021% ww, Ie I., Okinawa). Pharm: Cytotoxic (L1210, IC50 > 10 μg/mL). Ref: M. Tsuda, et al, Tet. Lett., 1999, 40, 5709│ H. Uemoto, et al, JNP, 2000, 63, 1050

H N

Br

OH H 11 15

O N H

O H

N H

N H

O

186

3 Pyrrole Indole and Imidazole Alkaloids

511 Slagenine B Type: Pyrrole-imidazole alkaloids. C12H15BrN4O4 Amorph. solid, [α]D26 = +33° (c = 0.2, MeOH). Source: Sponge Agelas nakamurai (yield = 0.0003% ww, Ie I., Okinawa). Pharm: Cytotoxic (L1210, IC50 = 7.5 μg/mL). Ref: M. Tsuda, et al, Tet. Lett., 1999, 40, 5709│ H. Uemoto, et al, JNP, 2000, 63, 1050│ B. Jiang, et al, Org. Lett., 2001, 3, 4011

H N

Br

O H 11 15

O N H

O

N H

N

H

H

O

512 Slagenine C Type: Pyrrole-imidazole alkaloids. C12H15BrN4O4 Amorph. solid, [α]D25 = −35° (c = 0.2, MeOH). Source: Sponge Agelas nakamurai (yield = 0.0003% ww, Ie I., Okinawa). Pharm: Cytotoxic (L1210, IC50 = 7.0 μg/mL). Ref: M. Tsuda, et al, Tet. Lett., 1999, 40, 5709│ H. Uemoto, et al, JNP, 2000, 63, 1050│ B. Jiang, et al, Org. Lett., 2001, 3, 4011 H

Br N H

O

H N

H

O

N O H

H N O

513 Spongiacidin A (E)-3-Bromohymenialdisine Type: Pyrrole-imidazole alkaloids. C11H9Br2N5O2 Amorph. solid. Source: Sponges Hymeniacidon sp. (Okinawa) and Stylissa carteri. Pharm: Kinase c-erbB-2 inhibitor (IC50 = 8.5 μg/mL). Ref: K. Inaba, et al, JNP, 1998, 61, 693│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) NH2 N O Br

NH E

Br N H O

N H

514 Spongiacidin B Type: Pyrrole-imidazole alkaloids. C11H10BrN5O2 Amorph. solid. Source: Sponge Hymeniacidon sp. Pharm: Kinase c-erbB-2 inhibitor (IC50 = 6.0 μg/mL). Ref: K. Inaba, et al, JNP, 1998, 61, 693│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev)

3.1 Pyrrole Alkaloids

187

NH2 N O Br

NH E

N H

N H O

515 Styloguanidine Isopalauamine Type: Pyrrole-imidazole alkaloids. C17H22ClN9O2 Amorph. solid, [α]D = +20.7° (c = 3.5, MeOH). Source: Sponge Stylotella aurantium (Yap Sea, Australia). Pharm: Chitinase inhibitor; antifoulant (inhibits moulting of cyprid larvae of barnacles, 10 ppm). Ref: T. Kato, et al, Tet. Lett., 1995, 36, 2133│ R. B. Kinnel, et al, JOC, 1998, 63, 3281│ M. S. Buchanan, et al, JOC, 2007, 72, 2309 3

2

H

NH

N H 2N OH HN

N H

N

12

H

N H 2N

Cl

O

H

NH2

17 19

516 Sventrine Type: Pyrrole-imidazole alkaloids. C12H13Br2N5O Light yellow powder. Source: Sponge Agelas sventres (Bahamas). Pharm: Antifeedant (reef fish Thalassoma bifasciatum). Ref: M. Assmann, et al, JNP, 2001, 64, 1593 Br

Br

N

H N N O

N H

NH2

517 Tauroacidin A Type: Pyrrole-imidazole alkaloids. C13H16Br2N6O5S Amorph. solid, [α]D28 = −4.3° (c = 0.1, MeOH). Source: Sponges Agelas sp. SS-1003 (off Seragaki, Okinawa), Axinella sp. (deep water, Great Australian Bight) and Hymeniacidon sp. (Okinawa). Pharm: Tyrosine kinase inhibitor; antibacterial (Staphylococcus aureus ATCC 25923, IC50 = 0.77 μmol/L, Staphylococcus aureus ATCC 9144, IC50 = 0.52 μmol/L, Bacillus subtilis ATCC 6051, IC50 = 0.70 μmol/L, Bacillus subtilis ATCC 6633, IC50 = 0.50 μmol/L, Escherichia coli ATCC 11775, IC50 = 0.62 μmol/L, Pseudomonas aeruginosa ATCC

188

3 Pyrrole Indole and Imidazole Alkaloids

10145, IC50 = 0.90 μmol/L); Epidermal Growth Factor Receptor (EGFR) inhibitor (IC50 = 20 μg/mL); kinase c-erbB-2 inhibitor (IC50 = 20 μg/mL). Ref: J. Kobayashi, et al, Tetrahedron, 1997, 53, 16679│ T. Endo, et al, JNP, 2004, 67, 1262│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev)│ H. Zhang, et al, Tet. Lett., 2012, 53, 3784 NH Br

Br

OH HN

H N

2

N H

O

N

S

N H

9

O

OH O

518 Tauroacidin B Type: Pyrrole-imidazole alkaloids. C13H17BrN6O5S Amorph. solid, [α]D28 = 0° (c = 0.1, MeOH). Source: Sponges Hymeniacidon sp. (Okinawa) and Hymeniacidon sp. Pharm: Epidermal Growth Factor Receptor (EGFR) inhibitor (IC50 = 20 μg/mL); kinase c-erbB-2 inhibitor (IC50 = 20 μg/mL). Ref: J. Kobayashi, et al, Tetrahedron 1997, 53, 16679│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) NH

Br H

OH H N

2

N

S

N

9

OH O

H

O

H

O

N

N

519 Taurodispacamide A Type: Pyrrole-imidazole alkaloids. C13H16Br2N6O4S Pale yellow solid. Source: Sponges Agelas sp. SS-1003 (off Seragaki, Okinawa), Axinella sp. (deep water, Great Australian Bight) and Agelas oroides. Pharm: Antibacterial (Staphylococcus aureus ATCC 25923, IC50 = 0.84 μmol/L, Staphylococcus aureus ATCC 9144, IC50 = 1.1 μmol/L, Bacillus subtilis ATCC 6051, IC50 = 1.4 μmol/L, Bacillus subtilis ATCC 6633, IC50 = 0.21 μmol/L, Escherichia coli ATCC 11775, IC50 = 0.74 μmol/L, Pseudomonas aeruginosa ATCC 10145, IC50 = 0.73 μmol/L); antifungal (Candida albicans ATCC 90028, IC50 = 1.2 μmol/L); antihistaminic (isolated guinea pig ileum, 10 μmol/L response of 0.1 μmol/L histamine was almost completely abolished in a reversible manner). Ref: E. Fattorusso,et al, Tet. Lett., 2000, 41, 9917│ T. Endo, et al, JNP, 2004, 67, 1262│ H. Zhang, et al, Tet. Lett., 2012, 53, 3784 NH Br

Br

N H

HN

H N

2

OH S

9

O

O

N N H

O

3.1 Pyrrole Alkaloids

189

520 Tubastrindole B Type: Pyrrole-imidazole alkaloids. C28H28N8O2 [α]D = −26° (c = 0.07, MeOH). Source: Sponge Smenospongia cerebriformis, stony coral Tubastraea sp. Pharm: α1 GlyR (glycine-gated chloride channel receptor) antagonist (IC50 = 25.9 μmol/L, potent and selective). Ref: T. Iwagawa,et al, Tet. Lett., 2003, 44, 2533│W. Balansa, et al, BoMC, 2013, 21, 4420

N

O 9

N H O

NH N

N N NH H

N

521 Aplysioviolin Type: Polypyrroles. C34H40N4O6 Mauve cryst. (CHCl3), mp 315 °C (dec), [α]D20 = +730° (c = 0.1, MeOH). Source: Sea hares Aplysia parvula, Aplysia limacina and Aplysia dactylomela. Pharm: Defensive secretion. Ref: J. Jongaramruong, et al, Aust. J. Chem., 2002, 55, 275

O O

H

O

O

NH

N H

N

HN

O

OH

522 Biliverdin Biliverdin IXα Type: Polypyrroles. C33H34N4O6 Dark blue-green cryst. with violet sheen (CHCl3), mp 300 °C. Source: blue coral Heliopora coerulea (major pigment), blue-green pigment of bile, eggshells and dog placenta, primary prod. derived from Haem in vivo. Pharm: Gives Gmelin reaction with conc. HNO3/CHCl3; reduced to Bilirubin in mammals. Ref: R. Lemberg, et al, Haematin Compounds and Bile Pigments, Interscience, N.Y., 1949│ W. Rüdiger, et al, Annalen, 1968, 713, 209│ W. S. Sheldrick, JCS Perkin II, 1976, 1457

190

3 Pyrrole Indole and Imidazole Alkaloids

O O

16

NH

N H

H N

N

15

O

O

OH

OH

523 Bonellin Type: Polypyrroles. C31H34N4O4 Green needles. Source: Spoon worm Bonellia viridis. Pharm: Sexual differentiation factor; larvicide. Ref: A. Pelter, Pure Appl. Chem., 1979, 51, 1847

N

N H N

HN

O

O HO

OH

524 Chlorophyllone a Type: Polypyrroles. C33H32N4O3 Dark green pigment. Source: Clam Ruditapes philippinarum, oyster Crassostrea sp., scallop Patinopecten yessoensis, plankton blooms and sediments. Pharm: Antioxidant. Ref: N. Watanabe, et al, JNP, 1993, 56, 305

NH

N

N

HN

H OH O O

3.1 Pyrrole Alkaloids

191

525 Corallistin A Type: Polypyrroles. C32H34N4O4 Source: Lithistid sponge Corallistes sp. (Coral Sea). Pharm: Phototherapeutic agent. Ref: M. D'Ambrosio, et al, Helv. Chim. Acta, 1989, 72, 1451

N

NH

O N

OH

HN O

OH

526 Cycloprodigiosin hydrochloride Type: Polypyrroles. C20H23N3O Source: Marine bacteria Alteromonas rubra and Beneckea gazogenes. Pharm: Immune system activity (IL-8 inhibitor, IC50 = 1 μmol/L, MMOA: AP-1 transcription factor inhibition). Ref: N. N. Gerber, Tet. Lett., 1983, 24, 2797│ K. Kawauchi, et al, Biol. Pharm. Bull. 2007, 30, 1792 O

N HN

NH

527 Phaeophytin A Pheophytin A5; Pheophytin A Type: Polypyrroles. C55H74N4O5 Source: Brown alga Sargassum fulvellum, numerous plant spp. Pharm: Nervous system activity (neurite outgrowth inducer, IC50 (apparent) > 3.9 μmol/L, MMOA: MAP kinase activation, promotes the differentiation of PC12 cells). Ref: A. Ina, et al, Int. J. Dev. Neurosci. 2007, 25, 63

N

NH N

HN

O O

O

O O

192

3 Pyrrole Indole and Imidazole Alkaloids

528 Pheophorbide a Type: Polypyrroles. C35H36N4O5 Source: Brown alga Laminaria japonica. Pharm: Hypoglycemic (AGE formation inhibition, in vitro assay, IC50 = 49.43 μmol/L); hypoglycemic (Aldose reductase inhibitor (rat lens aldose reductase RLAR in vitro assay, IC50 = 12.31 μmol/L)). Ref: Y. K. Son, et al, Fish. Sci., 2011, 77, 1069

NH N

N HN

O O

O O

OH

529 Pheophytin a Type: Polypyrroles. C55H74N4O5 Source: Brown alga Laminaria japonica. Pharm: Hypoglycemic (AGE formation inhibition, in vitro assay, IC50 = 228.71 μmol/L); hypoglycemic (Aldose reductase inhibitor (rat lens aldose reductase RLAR in vitro assay, IC50 > 100 μmol/L)). Ref: Y. K. Son, et al, Fish. Sci., 2011, 77, 1069

NH N

N HN

O

O O

O

O 3

530 Prodigiosin Type: Polypyrroles. C20H25N3O Lustrous dark red square pyramids, mp 151–152 °C. Source: Marine bacterium Hahella chejuensis. Pharm: Immune system activity (macrophage iNOS inhibitor, IC50 (apparent) = 0.1 μg/mL, MMOA: NF-κB transcription factor inhibition). Ref: J. E. Huh, et al, Int. Immunopharmacol. 2007, 7, 1825

3.1 Pyrrole Alkaloids

193

O N H

N H N

531 Tolyporphin A Type: Polypyrroles. C40H46N4O10 Dark purple cryst., [α]D = +3° (c = 0.1, MeOH). Source: Cyanobacterium Tolypothrix nodosa UH strain HT-58-2. Pharm: Cytotoxic (EMT-6, acts as photosensitizer); multidrug resistance reversing agents (10 μg/mL, less well efficiently for azidopine binding site on P-glycoprotein than did 10 μmol/L verapamil). Ref: M. R. Prinsep, et al, Tetrahedron, 1995, 51, 10523│ P. Morliere, et al, Cancer Res., 1998, 58, 3571 O HO

7

O 2A

H O

N

N H

H N

N

17

O

HO

O O 2B

H O

O

532 Tolyporphin B Type: Polypyrroles. C38H44N4O9 Red-purple solid. Source: Cyanobacterium Tolypothrix nodosa. Pharm: Multidrug resistance reversing agents (10 μg/mL, less well efficiently for azidopine binding site on P-glycoprotein than did 10 μmol/L verapamil). Ref: M. R. Prinsep, et al, Tetrahedron, 1995, 51, 10523

194

3 Pyrrole Indole and Imidazole Alkaloids

O

HO

7

O 2A

H O

N

N H

H N

N

17

O O O

HO

2B

H OH

533 Tolyporphin C Type: Polypyrroles. C38H44N4O9 Red-purple solid. Source: Cyanobacterium Tolypothrix nodosa. Pharm: Multidrug resistance reversing agents (10 μg/mL, less well efficiently for azidopine binding site on P-glycoprotein than did 10 μmol/L verapamil). Ref: M. R. Prinsep, et al, Tetrahedron, 1995, 51, 10523 O

HO

7

O 2A

H

N

N H

H N

N

17

OH

HO

O O 2B

H O

O

534 Tolyporphin D Type: Polypyrroles. C36H42N4O8 Red-brown solid, [α]D = +45° (c = 0.1, MeOH). Source: Cyanobacterium Tolypothrix nodosa. Pharm: Multidrug resistance reversing agents (10 μg/mL, more efficiently for azidopine binding site on P-glycoprotein than did 10 μmol/L verapamil). Ref: M. R. Prinsep, et al, Tetrahedron, 1995, 51, 10523

3.1 Pyrrole Alkaloids

195

O

HO

7

O 2A

H

N

N H

H N

N

17

OH O O

HO

2B

H OH

535 Tolyporphin E Type: Polypyrroles. C34H36N4O8 Dark red solid, [α]D = +52° (c = 0.1, MeOH). Source: Cyanobacterium Tolypothrix nodosa. Pharm: Multidrug resistance reversing agents (10 μg/mL, very poorly efficiently for azidopine binding site on P-glycoprotein than did 10 μmol/L verapamil). Ref: M. R. Prinsep, et al, Tetrahedron, 1995, 51, 10523 O O 7

O

N

N H

H N

N

17

O HO

O 2B

H O

O

536 Tolyporphin F Type: Polypyrroles. C32H34N4O7 Red-brown solid, [α]D = +20° (c = 0.05, MeOH). Source: Cyanobacterium Tolypothrix nodosa. Pharm: Multidrug resistance reversing agents (10 μg/mL, less well efficiently for azidopine binding site on P-glycoprotein than did 10 μmol/L verapamil). Ref: M. R. Prinsep, et al, Tetrahedron, 1995, 51, 10523

196

3 Pyrrole Indole and Imidazole Alkaloids

O 7

HO

N

N H

H N

N

17

O

HO

O 2B

H O

O

537 Tolyporphin G Type: Polypyrroles. C26H24N4O5 Red-brown solid. Source: Cyanobacterium Tolypothrix nodosa. Pharm: Multidrug resistance reversing agents (mixture with Tolyporphin H 10 μg/mL, more efficiently for azidopine binding site on P-glycoprotein than did 10 μmol/L verapamil). Ref: M. R. Prinsep, et al, Tetrahedron, 1995, 51, 10523 O O 7

O

N

N H

H N

N 17

OH O

538 Tolyporphin H Type: Polypyrroles. C26H24N4O5 Red-brown solid. Source: Cyanobacterium Tolypothrix nodosa. Pharm: Multidrug resistance reversing agents (mixture with Tolyporphin G 10 μg/mL, more efficiently for azidopine binding site on P-glycoprotein than did 10 μmol/L verapamil). Ref: M. R. Prinsep, et al, Tetrahedron, 1995, 51, 10523

3.2 Pyrrolidine Alkaloids

197

O 7

HO

N

N H

H N

N

O 17

O O

539 Tolyporphin I Type: Polypyrroles. C28H26N4O6 Red-pink solid, [α]D = +64° (c = 0.13, MeOH). Source: Cyanobacterium Tolypothrix nodosa. Pharm: Multidrug resistance reversing agents (10 μg/mL, very poorly efficiently for azidopine binding site on P-glycoprotein than did 10 μmol/L verapamil). Ref: M. R. Prinsep, et al, Tetrahedron, 1995, 51, 10523 O O 7

O

N

N H

H N

N

O 17

O O

3.2 Pyrrolidine Alkaloids 540 Amathamide C Type: Pyrrolidine alkaloids. C16H20Br3N2O21+ Source: Bryozoans Amathia wilsoni (Point Peur, Tasman Penninsula, Tasmania, Australia) and Amathia wilsoni. Pharm: Antiplasmodial (CSPF and CRPF, moderate growth inhibitor). Ref: A. J. Blackman, et al, Aust. J. Chem., 1987, 40, 1655│ A. R. Carroll, et al, Org. Biomol. Chem., 2011, 9, 604 Br O

Br

Br

N O

H

N H

+

198

3 Pyrrole Indole and Imidazole Alkaloids

541 Amathamide H Type: Pyrrolidine alkaloids. C16H20Br3N2O21+ Source: Bryozoan Amathia wilsoni (Point Peur, Tasman Penninsula, Tasmania, Australia). Pharm: Antiplasmodial (CSPF and CRPF, moderate growth inhibitor). Ref: A. R. Carroll, et al, Org. Biomol. Chem., 2011, 9, 604 Br O Br

Br

N O

H

N

+

H

542 Amathaspiramide A Type: Pyrrolidine alkaloids. C16H20Br2N2O3 Amorph. solid, [α]D25 = −3° (c = 0.0045, MeOH). Source: Bryozoan Amathia wilsoni (New Zealand). Pharm: Cytotoxic (BSC-1, 40 μg/well, 1+, moderate); antibacterial (gram-positive bacterium Bacillus subtilis, 60 μg/disk, inhibition zone = 1 mm, mild); antifungul (Trichophyton mentagrophytes, 60 μg/disk, inhibition zone = 1 mm, mild). Ref: B. D. Morris, et al, JNP, 1999, 62, 688 Br O

H

Br OH

2 1

8

N

N O

543 Amathaspiramide E Type: Pyrrolidine alkaloids. C15H16N2O3Br2 Amorph. solid, [α]D25 = −21° (c = 0.0023, MeOH). Source: Bryozoan Amathia wilsoni (New Zealand). Pharm: Antiviral (virus Polio sp., 40 μg/well, 4+, strong); cytotoxic (BSC-1, 40 μg/well, 1+, moderate); antibacterial (gram-positive bacterium Bacillus subtilis, 60 μg/disk, inhibition zone = 1 mm, mild); antifungal (Trichophyton mentagrophytes, 60 μg/disk, inhibition zone = 1 mm, mild). Ref: B. D. Morris, et al, JNP, 1999, 62, 688 Br O

H

Br OH

2

1

N

N O

3.2 Pyrrolidine Alkaloids

199

544 Barmumycin Type: Pyrrolidine alkaloids. C15H19NO4 [α]D = −51.2° (c = 0.25, CH2Cl2). Source: Marine-derived streptomycete Streptomyces sp. BOSC-022A from an unidentified ascidian (Scottish Coast). Pharm: Cytotoxic (12 cancer, micromolar concentrations). Ref: A. Lorente, et al, JOC, 2010, 75, 8508 HO N

O O

OH

545 Convolutamide A Type: Pyrrolidine alkaloids. C24H35Br2NO4 Amorph. solid, [α]D20 = −6° (c = 0.4, CHCl3). Source: Bryozoan Amathia convoluta (Florida). Pharm: Cytotoxic (P388, L1210, KB). Ref: H. Zhang, et al, Chem. Lett., 1994, 2271│ H. Zhang, et al, Tetrahedron, 1994, 50, 10201 HO

HO

N O

O

Br Br

546 Convolutamide B Type: Pyrrolidine alkaloids. C26H37Br2NO4 Source: Bryozoan Amathia convoluta (Florida). Pharm: Cytotoxic (P388, L1210, KB). Ref: H. Zhang, et al, Chem. Lett., 1994, 2271│ H. Zhang, et al, Tetrahedron, 1994, 50, 10201 HO

HO

N O

O

Br Br

547 Convolutamide D Type: Pyrrolidine alkaloids. C28H41Br2NO4 Source: Bryozoan Amathia convoluta (Florida). Pharm: Cytotoxic (P388, L1210, KB). Ref: H. Zhang, et al, Chem. Lett., 1994, 2271│ H. Zhang, et al, Tetrahedron, 1994, 50, 10201

HO

HO

N O

Br Br

O

200

3 Pyrrole Indole and Imidazole Alkaloids

548 Convolutamide E Type: Pyrrolidine alkaloids. C28H43Br2NO4 Amorph. solid, [α]D20 = −25° (c = 0.1, CHCl3). Source: Bryozoan Amathia convoluta (Florida). Pharm: Cytotoxic (P388, L1210, KB). Ref: H. Zhang, et al, Chem. Lett., 1994, 2271│ H. Zhang, et al, Tetrahedron, 1994, 50, 10201

HO

HO

N O

O

Br Br

549 Convolutamide F Type: Pyrrolidine alkaloids. C30H45Br2NO4 Source: Bryozoan Amathia convoluta (Florida). Pharm: Cytotoxic (P388, L1210, KB). Ref: H. Zhang, et al, Chem. Lett., 1994, 2271│ H. Zhang, et al, Tetrahedron, 1994, 50, 10201 HO

N

HO

O

O

Br Br

550 Domoic acid Type: Pyrrolidine alkaloids. C15H21NO6 Needles + 2H2O, mp 213 °C (dec), [α]D12 = −109.6° (H2O). Source: Diatom Nitzschia pungens f. multiseries (psychrophilic, cold water), related diatoms (along Pacific coast of North and Central America, in New Zealand, and in Europe), red algae Chondria armata and Alsidium corallinum, mussel Mytilus edulis. Pharm: Neurotoxin; amnesic shellfish poison; vermifuge; insecticide; ionotropic glutamate (kainate) receptor agonist; LD50 (mice) = 10 mg/kg. Ref: G. Impellizzeri, et al, Phytochemistry, 1975, 14, 1549│ J. L. C. Wright, et al, Can. J. Chem., 1989, 67, 481; 1990, 68, 22│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) OH

O H 1'

O

H

3'

O

5'

HO

N H

OH

3.2 Pyrrolidine Alkaloids

201

551 Dysidamide Type: Pyrrolidine alkaloids. C15H21Cl6NO3 Needles (petrol), mp 133 °C, mp 123–124 °C, [α]D = −16.1° (c = 2.76, CH2Cl2). Source: Sponge Lamellodysidea herbacea (Red Sea). Pharm: Neurotoxin. Ref: S. Isaacs, et al, JNP, 1991, 54, 83│ Sauleau, P. et al, Tetrahedron, 2005, 61, 955 HO 4 5

3'

Cl

N

Cl

O

Cl O 3S

Cl

Cl Cl

552 Dysideapyrrolidone Type: Pyrrolidine alkaloids. C17H22Cl6N2O4 Prisms, mp 165–166 °C, [α]D = +16.6° (c = 0.4, CHCl3). Source: Sponge Dysidea herbacea (Palau, Oceania). Pharm: Antifeedant. Ref: M. D. Unson, et al, JOC, 1993, 58, 6336 O O N O

Cl Cl Cl

HN O

Cl Cl Cl

553 Dysidine (1977) Type: Pyrrolidine alkaloids. C16H22Cl3NO4 Needles (hexane), mp 127–129 °C, [α]D25 = +141° (c = 1, CHCl3). Source: Sponge Dysidea herbacea (Townsville). Pharm: LD50 (mus, ipr) = 40–80 mg/kg. Ref: P. G. Williard, et al, JOC, 1984, 49, 3489│ F. J. Schmitz, et al, JNP, 1988, 51, 745 O

O

N O

O Cl Cl

Cl

202

3 Pyrrole Indole and Imidazole Alkaloids

554 Epolactaene Type: Pyrrolidine alkaloids. C21H27NO6 Amorph. solid, [α]D26 = +32° (c = 0.1, MeOH). Source: Marine-derived fungus Penicillium sp. BM1689-P (sea bottom sediment, Uchiura Bay, Japan). Pharm: Neuritogenic (in hmn neuroblastoma cells); DNA polymerases (mammalian) inhibitor; DNA topoisomerase II inhibitor. Ref: H. Kakeya, et al, J. Antibiotics, 1995, 48, 733│ H. Kakeya,et al, JMC, 1997, 40, 391 │ Y. Mizushina, et al, Biochem. Biophys. Res. Commun., 2000, 273, 784 O O

HO

O

N

O

O

H

555 Ircinamine Type: Pyrrolidine alkaloids. C19H33NO2S Amorph. solid. Source: Sponge Ircinia sp. Pharm: Cytotoxic (P388, LD50 = 24.6 μg/mL; marked biological activity is still expected based on reactivity of the thioester moiety). Ref: G. Fenteany,et al, Science, 1995, 268, 726│ M. Kuramoto, et al, Chem. Lett., 2002, 464│ M. Kuramoto, et al, Mar. Drugs, 2004, 2, 39 O O N

S

H

556 Isodomoic acid A Type: Pyrrolidine alkaloids. C15H21NO6 mp 185–187 °C (dec), [α]D25 = −70° (c = 0.1, H2O). Source: Red alga Chondria armata, diatom Nitzschia navis-varingica. Pharm: Anthelminthic; insecticide. Ref: M. Maeda, et al, CPB, 1986, 34, 4892 OH O 1' H H O N H

O

OH

OH

557 Isodomoic acid B Type: Pyrrolidine alkaloids. C15H21NO6 mp 182–183 °C (dec), [α]D25 = −8.1° (c = 0.14, H2O). Source: Red alga Chondria armata, diatom Nitzschia navis-varingica. Pharm: Anthelminthic; insecticide; vermifuge. Ref: M. Maeda, et al, CPB, 1986, 34, 4892

3.2 Pyrrolidine Alkaloids

203

OH O H

O

H O

1'E

OH N H

OH

558 Isodomoic acid C Type: Pyrrolidine alkaloids. C15H21NO6 mp 257–260 °C (dec), [α]D25 = −30° (c = 0.015, H2O). Source: Red alga Chondria armata, diatom Nitzschia navis-varingica. Pharm: Insecticide. Ref: P. T. Holland, et al, Chem. Res. Toxicol., 2005, 18, 814 OH O 1' H H O N H

O

OH

OH

559 Isodomoic acid G Type: Pyrrolidine alkaloids. C15H21NO6 Source: Red alga Chondria armata (Japan waters). Pharm: Neurotoxin. Ref: L. Zaman, et al, Toxicon, 1997, 35, 205 O HO

OH H

O OH

N H

O

560 Isodomoic acid H Type: Pyrrolidine alkaloids. C15H21NO6 Source: Red alga Chondria armata (Japan waters). Pharm: Neurotoxin. Ref: L. Zaman, et al, Toxicon, 1997, 35, 205

OH O

4Z

OH

H

O OH

N H

O

204

3 Pyrrole Indole and Imidazole Alkaloids

561 Jamaicamide A Type: Pyrrolidine alkaloids. C27H36BrClN2O4 Pale yellow oil, [α]D25 = +44° (c = 1.5, MeOH). Source: Cyanobacterium Lyngbya majuscula. Pharm: Cytotoxic (MTT assay, H460 and neuro-2a, LC50 = 15 μmol/L); Na channel blocker (5 μmol/L, 0.15 μmol/L producing approximately half the response of saxitoxin); neurotoxic (goldfish toxicity assay, sublethal toxicity at 5 ppm after 90 min). Ref: D. J. Edwards, et al, Chem. Biol. 2004, 11, 817 Cl Br N

O

20

19

H N

O

O

O

562 Jamaicamide B Type: Pyrrolidine alkaloids. C27H37ClN2O4 Pale yellow oil, [α]D25 = +53° (c = 0.61, MeOH). Source: Cyanobacterium Lyngbya majuscula. Pharm: Cytotoxic (MTT assay, H460 and neuro-2a, LC50 = 15 μmol/L); Na channel blocker (5 μmol/L, 0.15 μmol/L producing approximately half the response of saxitoxin); neurotoxic (goldfish toxicity assay, 100% lethality at 5 ppm after 90 min). Ref: D. J. Edwards, et al, Chem. Biol. 2004, 11, 817 Cl 19 20

N O

O

H N O

O

563 Jamaicamide C Type: Pyrrolidine alkaloids. C27H39ClN2O4 Pale yellow oil, [α]D25 = +49° (c = 0.39, MeOH). Source: Cyanobacterium Lyngbya majuscula. Pharm: Cytotoxic (MTT assay, H460 and neuro-2a, LC50 = 15 μmol/L); Na channel blocker (5 μmol/L, 0.15 μmol/L producing approximately half the response of saxitoxin); neurotoxic (goldfish toxicity assay, 100% lethality at 10 ppm after 90 min); toxic (brine shrimp, at 10 ppm, 25% lethality). Ref: D. J. Edwards, et al, Chem. Biol. 2004, 11, 817

3.2 Pyrrolidine Alkaloids

205

Cl

20 19

O

N

H N

O

O

O

564 Mycapolyol A Type: Pyrrolidine alkaloids. C55H94N2O18 Powder, [α]D21 = +101.1° (c = 0.34, MeOH aq). Source: Sponge Mycale izuensis. Pharm: Cytotoxic (HeLa, IC50 = 0.06 μg/mL). Ref: P. Phuwapraisirisan, et al, Org. Lett., 2005, 7, 2233 O

O N

HN

O 7

O

10

OH

OH

OH

OH

OH

565 Mycapolyol B Type: Pyrrolidine alkaloids. C53H90N2O17 Powder, [α]D27 = +104.7° (c = 0.22, MeOH aq). Source: Sponge Mycale izuensis. Pharm: Cytotoxic (HeLa, IC50 = 0.05 μg/mL). Ref: P. Phuwapraisirisan, et al, Org. Lett., 2005, 7, 2233 O

O N

HN

O 10

7

O

OH

OH

OH

OH

566 Mycapolyol C Type: Pyrrolidine alkaloids. C51H86N2O16 Powder, [α]D27 = +105.7° (c = 0.32, MeOH aq). Source: Sponge Mycale izuensis. Pharm: Cytotoxic (HeLa, IC50 = 0.16 μg/mL). Ref: P. Phuwapraisirisan, et al, Org. Lett., 2005, 7, 2233 O

O N

O

HN

O 9

7

OH

OH

OH

OH

206

3 Pyrrole Indole and Imidazole Alkaloids

567 Mycapolyol D Type: Pyrrolidine alkaloids. C49H82N2O15 Powder, [α]D27 = +100.6° (c = 0.25, MeOH aq). Source: Sponge Mycale izuensis. Pharm: Cytotoxic (HeLa, IC50 = 0.40 μg/mL). Ref: P. Phuwapraisirisan, et al, Org. Lett., 2005, 7, 2233 O

O N

HN

O 8

7

O

OH

OH

OH

OH

568 Mycapolyol E Type: Pyrrolidine alkaloids. C47H78N2O14 Powder, [α]D21 = +117.7° (c = 0.27, MeOH aq). Source: Sponge Mycale izuensis. Pharm: Cytotoxic (HeLa, IC50 = 0.38 μg/mL). Ref: P. Phuwapraisirisan, et al, Org. Lett., 2005, 7, 2233 O

O N

HN

O 7

7

O

OH

OH

OH

OH

569 Mycapolyol F Type: Pyrrolidine alkaloids. C45H74N2O13 Powder, [α]D21 = +120.1° (c = 0.2, MeOH aq). Source: Sponge Mycale izuensis. Pharm: Cytotoxic (HeLa, IC50 = 0.90 μg/mL). Ref: P. Phuwapraisirisan, et al, Org. Lett., 2005, 7, 2233 O

O N

HN

O 6

7

O

OH

OH

OH

OH

570 Nordomoic acid Type: Pyrrolidine alkaloids. C14H19NO6 Source: Red alga Chondria armata. Pharm: Insecticide. Ref: M. Maeda, et al, CA, 1986, 104, 183260t O H O HO

H N H

OH O OH

3.2 Pyrrolidine Alkaloids

207

571 15-Norpseurotin A Type: Pyrrolidine alkaloids. C21H23NO8 Pale yellow powder, [α]D25 = −6.5° (c = 0.12, MeOH). Source: Marine-derived fungus Aspergillus sydowi PFW1-13 from driftwood (China Waters). Pharm: Antibacterial (disk diffusion method, Escherichia coli, MIC = 3.74 μmol/L; Bacillus subtilis, MIC = 14.97 μmol/L; Micrococcus lysoleikticus, MIC = 7.49 μmol/L). Ref: M. Zhang, et al, JNP, 2008, 71, 985 OH

O O

H O N

Z

OH

O O

OH

572 Plakoridine A Type: Pyrrolidine alkaloids. C35H57NO5 Colorless oil, [α]D19 = −0.4° (c = 0.5, CHCl3). Source: Sponge Plakortis sp. (Okinawa). Pharm: Cytotoxic (mus in vitro, L1210, IC50 = 1.0 μg/mL). Ref: S. Takeuchi, et al, JOC, 1994, 59, 3712 O HO OH

H

N

O O

573 Pseurotin A Type: Pyrrolidine alkaloids. C22H25NO8 Rhombic cryst. (CH2Cl2/hexane), mp 162– 163.5 °C, [α]D25 = −5° (MeOH). Source: Marine-derived fungus Aspergillus sydowi PFW1-13 (from driftwood sample, China), marine-derived fungus Aspergillus fumigatus, terrestrial fungus (Aspergillus fumigatus). Pharm: Antibacterial (disk diffusion assay, Escherichia coli, MIC = 14.49 μmol/L; Bacillus subtilis, MIC = 14.49 μmol/L; Micrococcus lysoleikticus, MIC = 7.24 μmol/L); monoamine oxidase inhibitor; chitin synthase inhibitor; apomorphine antagonist; nerve growth factor; nematocide. Ref: N. C. Gassner, et al, JNP, 2007, 70, 383│ C. M. Boot, et al, JNP, 2007, 70, 1672│ M. Zhang, et al, JNP, 2008, 71, 985 OH

O O

H O N

Z

OH

O O

OH

574 Pulchellalactam Type: Pyrrolidine alkaloids. C9H13NO Source: Marine-derived fungus Corollospora pulchella (Peleliu I., Palau, Oceania, cultured from drifewood). Pharm: CD45

208

3 Pyrrole Indole and Imidazole Alkaloids

phosphatase inhibitor (CD45 plays central signaling roles by dephosphorylating Srckinases and therefore represents an attractive drug target). Ref: K. A. Alvi, et al, J. Antibiot., 1998, 51, 515│ J. Irie-Sasaki, et al, Curr. Top. Med. Chem., 2003, 3, 783.

H N

O

575 Scalusamide A Type: Pyrrolidine alkaloids. C16H27NO3 Amorph. solid, [α]D22 = −28° (c = 1, CHCl3). Source: Marine-derived fungus Penicillium citrinum N055 (cultured broth) from an unidentified fish (gastrointestine). Pharm: Antifungal (Cryptococcus neoformans, MIC = 16.7 μg/mL); antibacterial (Micrococcus luteus, MIC = 33.3 μg/mL). Ref: M. Tsuda, et al, JNP, 2005, 68, 273│ M. Saleem, et al, NPR, 2007, 24, 1142 (rev) OH 13

N O

O

576 Villatamine A Type: Pyrrolidine alkaloids. C18H29N Oil, [α]D = +49° (MeOH). Source: Flatworm Prostheceraeus villatus (psychrophilic, cold water, waters off Bergen, Norway), ascidian Clavelina lepadiformis (prey of flatworm Prostheceraeus villatus). Pharm: Cytotoxic. Ref: J. Kubanek, et al, Tet. Lett., 1995, 36, 6189│ J. Kubanek, et al, Tet. Lett., 1995, 36, 6189│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)

N

577 Villatamine B Type: Pyrrolidine alkaloids. C18H33N Oil, [α]D = +15° (MeOH). Source: Flatworm Prostheceraeus villatus (psychrophilic, cold water, waters off Bergen, Norway), ascidian Clavelina lepadiformis (prey of flatworm Prostheceraeus villatus). Pharm: Cytotoxic (P388, ED50 = 11.4 μg/mL; MCF7, ED50 = 2.8 μg/mL; U373, ED50 = 1.9 μg/mL; HEY, ED50 = 2.8 μg/mL; LoVo, ED50 = 1.7 μg/mL; A549, ED50 = 2.8 μg/mL). Ref: J. Kubanek, et al, Tet. Lett., 1995, 36, 6189│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)

3.2 Pyrrolidine Alkaloids

209

N

578 Ypaoamide Type: Pyrrolidine alkaloids. C26H36N2O5 [α]D19 = +197° (c = 1.0, CHCl3). Source: Cyanobacterium Lyngbya majuscula (Guam). Pharm: Antifeedant (broad actions). Ref: D. G. Nagle, et al, Tet. Lett., 1996, 37, 6263 O O

N

H N

O HO

O

579 Aburatubolactam A Type: 2,4-Pyrrolidinediones. C30H40N2O5 Source: Marine-derived streptomycete Streptomyces sp. from an unidentified mollusk. Pharm: Antioxydant (hmn neutrophils, inhibited TPA-induced superoxide anion generation, IC50 = 26 μg/mL); cytotoxic; apoptosis inducer. Ref: M. Kuramoto, et al, Mar. Drugs, 2004, 2, 39│ M. -A. Bae, et al, Heterocycl. Commun., 1996, 2, 315 H

H N O

H

OH

O

OH

H H N

O

H

580 Aburatubolactam B Type: 2,4-Pyrrolidinediones. C30H40N2O6 Cryst., [α]D = +197° (Py). Source: Marinederived streptomycete Streptomyces sp. Pharm: Antioxydant (hmn neutrophils, inhibited TPA-induced superoxide anion generation, IC50 = 6.3 μg/mL); anti-inflammatory; cytotoxic. Ref: M. Kuramoto, et al, Mar. Drugs, 2004, 2, 39│ M. -A. Bae, et al, J. Microbiol. Biotechnol., 1998, 8, 455 O H N O OH OH O

N O

210

3 Pyrrole Indole and Imidazole Alkaloids

581 Aburatubolactam C Type: 2,4-Pyrrolidinediones. C30H40N2O5 Powder, [α]D = +136° (Py). Source: Marinederived streptomycete Streptomyces sp. Pharm: Antioxydant (hmn neutrophils, inhibited TPA-induced superoxide anion generation, IC50 = 2.7 μg/mL); anti-inflammatory; cytotoxic; apoptosis inducer. Ref: M. Kuramoto, et al, Mar. Drugs, 2004, 2, 39│ M. -A. Bae, et al, J. Microbiol. Biotechnol., 1998, 8, 455 O H N O OH

O

N O

582 Alteramide A Type: 2,4-Pyrrolidinediones. C29H38N2O6 Yellow powder, mp 200 °C (dec), [α]D22 = +36.2° (c = 0.1, MeOH). Source: Marine bacterium Alteromonas sp. from sponge Halichondria okadai. Pharm: Cytotoxic (P388, IC50 = 0.1 μg/mL; L1210, IC50 = 1.7 μg/mL; KB, IC50 = 5.0 μg/mL). Ref: H. Shigemori, et al, JOC, 1992, 57, 4317 H H N

H O

H H

O

OH 25

OH

HO N H

O

H

583 Ancorinoside A Type: 2,4-Pyrrolidinediones. C41H69NO17 Oil, [α]D25 = −5.5° (c = 0.09, MeOH). Source: Sponges Ancorina sp. (Japan waters) and Penares sollasi. Pharm: Inhibits starfish embryo blastulation; inhibits MT1-matrix metalloproteinase. Ref: S. Ohta, et al, JOC, 1997, 62, 6452│ M. Fujita, et al, Tetrahedron, 2001, 57, 1229 O

HO

OH

O O OH

OH OH

OO

OH O 19

O OH

N

O OH

OH

584 Ancorinoside B Type: 2,4-Pyrrolidinediones. C41H69NO17 White powder, [α]D24 = +1.5° (c = 0.1, MeOH). Source: Sponge Penares sollasi (depth of 15–20 m off Ukejima I., near Amami Oshima

3.2 Pyrrolidine Alkaloids

211

I., Japan, 129°13’40’’E 28°02’80”N). Pharm: Membrane type 1 matrix metalloproteinase (MT1-MMP) inhibitor (IC50 = 500 μg/mL, ancorinosides are 10 times less potent than FN-439, IC50 = 25 μg/mL, which encompasses a hydroxamate group. MMP inhibitors known to date contain either hydroxamate or carboxylate groups); MMP-2 inhibitor (IC50 = 33 μg/mL); cytotoxic (P388, IC50 > 20 μg/mL). Ref: M. Fujita, et al, Tetrahedron, 2001, 57, 1229

HO

OH

O

OH O

O

O

OH

O

HO

HO

O O

OH 19

OH

OH

N O

585 Ancorinoside C Type: 2,4-Pyrrolidinediones. C42H71NO17 White powder, [α]D24 = +2.8° (c = 0.1, MeOH). Source: Sponge Penares sollasi (depth of 15–20 m off Ukejima I., near Amami Oshima I., Japan, 129°13’40’’E 28°02’80”N). Pharm: Membrane type 1 matrix metalloproteinase (MT1-MMP) inhibitor (IC50 = 370 μg/mL, ancorinosides are 10 times less potent than FN-439, IC50 = 25 μg/mL, which encompasses a hydroxamate group. MMP inhibitors known to date contain either hydroxamate or carboxylate groups). Ref: M. Fujita, et al, Tetrahedron, 2001, 57, 1229 O HO

OH

O O

OH

OH

O

OO HO

OH

O

HO

8

12

OH

N

OH

O

586 Ancorinoside D Type: 2,4-Pyrrolidinediones. C41H67NO17 White powder, [α]D24 = −5.2° (c = 0.1, MeOH). Source: Sponge Penares sollasi (depth of 15–20 m off Ukejima I., near Amami Oshima I., Japan, 129°13’40’’E 28°02’80”N). Pharm: Membrane type 1 matrix metalloproteinase (MT1-MMP) inhibitor (IC50 = 180 μg/mL, ancorinosides are 10 times less potent than FN-439, IC50 = 25 μg/mL, which encompasses a hydroxamate group. MMP inhibitors known to date contain either hydroxamate or carboxylate groups). Ref: M. Fujita, et al, Tetrahedron, 2001, 57, 1229 OH O HO HO OH

O O

OH O

HO

OH

O O

O 8

11

OH

N O

OH

212

3 Pyrrole Indole and Imidazole Alkaloids

587 Aurantoside A Type: 2,4-Pyrrolidinediones. C36H46Cl2N2O15 Orange solid, [α]D23 = −568° (c = 0.1, MeOH). Source: Sponges Melophlus sp. (Cicia, Lau group of Fiji) and Melophlus sp. Pharm: Antifungal (Candida albicans, MIC = 11.3 μg/mL; Aspergillus fumigatus, MIC = 18.0 μg/mL); cytotoxic (P388, IC50 > 5.0 μg/mL). Ref: S. Matsunaga, et al, JACS, 1991, 113, 9690│ N. U. Sata, et al, JNP, 1999, 62, 969│ R. Kumar, et al, Mar. Drugs, 2012, 10, 200 Cl Cl

OH

O O

4

N

OH

O O

H2N

OH OH

O O O

OH

HO

O O

588 Aurantoside B Type: 2,4-Pyrrolidinediones. C35H44Cl2N2O15 Orange solid, [α]D23 = −492° (c = 0.1, MeOH). Source: Lithistid sponge Theonella sp. Pharm: Antifungal (Candida albicans, MIC = 11.8 μg/mL; Aspergillus fumigatus, MIC = 17.2 μg/mL); cytotoxic (P388, IC50 > 5.0 μg/mL). Ref: S. Matsunaga, et al, JACS, 1991, 113, 9690│ N. U. Sata, et al, JNP, 1999, 62, 969 OH

Cl

O Cl

O

E

NH2

O O

N

OH OH O

O OH

O HO

O OH

OH

589 Aurantoside C Type: 2,4-Pyrrolidinediones. C37H46Cl2N2O15 Amorph. red powder, [α]D20 = −480° (c = 0.2, CH2Cl2/MeOH 10:1). Source: Lithistid sponge Homophymia conferta

3.2 Pyrrolidine Alkaloids

213

(Philippines). Pharm: LC50 (brine shrimp) = 50 μg/mL. Ref: D. Wolf, et al, JNP, 1999, 62, 1711 Cl

Cl

OH

O

4

N

H 2N

OH

O O

O

OH OH O

OH

O O

O

HO

OH

590 Aurantoside D Type: 2,4-Pyrrolidinediones. C37H46Cl2N2O15 Red solid, [α]D24 = −536° (c = 0.001, MeOH). Source: Lithistid sponge Siliquariaspongia japonica (Japan waters). Pharm: Antifungal (Candida albicans, MIC = 9.5 μg/mL; Aspergillus fumigatus, MIC = 11.0 μg/mL); cytotoxic (P388, IC50 = 0.2 μg/mL). Ref: N. U. Sata, et al, JNP, 1999, 62. 969 Cl

Cl

OH

O

4

N O

O H 2N

O OH

OH OH

O

OH

O

O O OH HO

591 Aurantoside E Type: 2,4-Pyrrolidinediones. C38H48Cl2N2O15 Red solid, [α]D24 = −1038° (c = 0.001, MeOH). Source: Lithistid sponge Siliquariaspongia japonica (Japan waters). Pharm: Antifungal (Candida albicans, Aspergillus fumigatus, MIC = 9.7, 13.6 μg/mL respectively); cytotoxic (mus, P388 leukemia cell, IC50 = 0.2 μg/mL). Ref: N. U. Sata, et al, JNP, 1999, 62. 969 Cl

Cl

OH

O

4

N O

O H2N

O OH

O

OH OH OH

O

O O OH O

214

3 Pyrrole Indole and Imidazole Alkaloids

592 Aurantoside F Type: 2,4-Pyrrolidinediones. C40H50Cl2N2O15 Red solid, [α]D24 = −1012° (c = 0.001, MeOH). Source: Lithistid sponge Siliquariaspongia japonica (Japan waters). Pharm: Cytotoxic (P388, IC50 = 0.05 μg/mL). Ref: N. U. Sata, et al, JNP, 1999, 62. 969 Cl

Cl

OH

O

4

N O

O H2N

O OH

O

OH OH OH

O

O O OH O

593 Aurantoside K Type: 2,4-Pyrrolidinediones. C33H43ClN2O15 Orange solid, [α]D27 = −127° (c = 0.2, MeOH). Source: Sponge Melophlus sp. (Cicia, Lau group of Fiji). Pharm: Antifungal (wide spectrum: Candida albicans, MIC = 1.95 μg/mL; ARCA, MIC = 31.25 μg/mL, Cryptococcus neoformans, 100 μg/disc, IZD = 14 mm; Aspergillus niger, 100 μg/disc, IZD = 28 mm; Penicillium sp., 100 μg/disc, IZD = 31 mm; Rhizopus sporangia, 100 μg/disc, IZD = 21 mm; and Sordaria sp. 100 μg/disc, IZD = 29 mm). Ref: R. Kumar, et al, Mar. Drugs, 2012, 10, 200 Cl

OH

O O

4

N

OH

O O H 2N O O OH HO

OH OH

OH O

O

594 Cladosin C Type: 2,4-Pyrrolidinediones. C13H18N2O3 Pale yellow oil, [α]D24 = +10.5° (c = 0.10, MeOH). Source: Deep-sea fungus Cladosporium sphaerospermum 2005-01-E3. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 276 μmol/L, control Ribavirin, IC50 = 131 μmol/L). Ref: G. Wu, et al, JNP, 2014, 77, 270

3.2 Pyrrolidine Alkaloids

215

O OH

E

HN

NH2 O E is major

595 Cladosin Cmajor Type: 2,4-Pyrrolidinediones. C13H18N2O3 Source: Deep-sea fungus Cladosporium sphaerospermum 2005-01-E3. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 276 μmol/L). Ref: G. Wu, et al, JNP, 2014, 77, 270

OH

O

NH2 E

HN

O E is major

596 Cladosin Cminor Type: 2,4-Pyrrolidinediones. C13H18N2O3 Source: Deep-sea fungus Cladosporium sphaerospermum 2005-01-E3. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 276 μmol/L). Ref: G. Wu, et al, JNP, 2014, 77, 270 HO H 2N O Z

HN

O Z is minor

597 Cladosin F Type: 2,4-Pyrrolidinediones. C13H20N2O4 Source: Deep-sea fungus Cladosporium sphaerospermum 2005-01-E3. Pharm: Cytotoxic (in vitro, weak). Ref: G. Yu, et al, J. Asian Nat. Prod. Res., 2014, 17, 1

216

3 Pyrrole Indole and Imidazole Alkaloids

OH OH O

NH2 E

HN

O E is major, Z is minor

598 Cladosin G Type: 2,4-Pyrrolidinediones. C14H22N2O4 Source: Deep-sea fungus Cladosporium sphaerospermum 2005-01-E3. Pharm: Cytotoxic (in vitro, weak). Ref: G. Yu, et al, J. Asian Nat. Prod. Res., 2014, 17, 1

OH O O E

HN

NH2 O

E is major, Z is minor

599 Cylindramide Type: 2,4-Pyrrolidinediones. C27H34N2O5 Wax, [α]D25 = +175° (c = 0.4, MeOH). Source: Sponge Halichondria cylindrata (Japan waters). Pharm: Cytotoxic. Ref: S. Kanazawa, et al, Tet. Lett., 1993, 34, 1065 O H HN

17 29

H

HO O

H NH O

OH

600 Equisetin Type: 2,4-Pyrrolidinediones. C22H31NO4 Source: Marine-derived fungus Fusarium heterosporum. Pharm: Anti-HIV (IC50 = 15 μmol/L). Ref: S. B. Singh, et al, Tet. Lett., 1999, 40, 8775

3.2 Pyrrolidine Alkaloids

217

H

HO

H O

HO O

N

601 Geodin A 17,29-Didehydro-cylindramide Mg salt (2:1) Type: 2,4-Pyrrolidinediones. C54H64MgN4O10 Amorph. solid, mp 173 °C (dec), [α]D20 = +179° (c = 1.0, DMSO). Source: Sponge Geodia sp. (Southern Australia). Pharm: Nematocide (LD99 = 1 μg/mL). Ref: R. J. Capon, et al, JNP, 1999. 62, 1256 O

Mg

2+

H HN

17 29

HO

H

H

O

NH O O

2

602 Magnesidin Type: 2,4-Pyrrolidinediones. C32H44MgN2O8 Sol. MeOH, Et2O; poorly sol. H2O. Source: Marine bacterium Vibrio zagogenes ATCC29988 (from marine mud sample). Pharm: Antibacterial (gram-positive bacteria, particularly the spore bearers). Ref: N. Imamura, et al, J. Antibiot., 1994, 47, 257

O

O N Z/E

O Mg O

O O

Z/E

N O

O

603 Penicillenol A1 Type: 2,4-Pyrrolidinediones. C16H27NO4 Yellow oil, [α]D25 = −864.5° (c = 0.155, MeOH). Source: Mangrove-derived fungus Penicillium sp. GQ-7 from mangrove Aegiceras

218

3 Pyrrole Indole and Imidazole Alkaloids

corniculatum (bark, China). Pharm: Cytotoxic (HL60, moderate). Ref: Z. H. Lin, et al, CPB, 2008, 56, 217 6' 7'

O H

OH 5

N

6

O

OH

604 Penicillenol A2 Type: 2,4-Pyrrolidinediones. C16H27NO4 Yellow oil, [α]D25 = +386.7° (c = 0.13, MeOH). Source: Mangrove-derived fungus Penicillium sp. GQ-7 from mangrove Aegiceras corniculatum (bark, China). Pharm: Cytotoxic (HL60, moderate). Ref: Z. H. Lin, et al, CPB, 2008, 56, 217 6' 7'

O H

OH 5

6

N

O

OH

605 Penicillenol B1 Type: 2,4-Pyrrolidinediones. C16H25NO3 Yellow oil, [α]D25 = −7.8° (c = 0.23, MeOH). Source: Mangrove-derived fungus Penicillium sp. GQ-7 from mangrove Aegiceras corniculatum (bark, China). Pharm: Cytotoxic (HL60, moderate). Ref: Z. H. Lin, et al, CPB, 2008, 56, 217 6' 7'

O H

Z 6

OH 5

N

O

606 Penicillenol B2 Type: 2,4-Pyrrolidinediones. C16H25NO3 Yellow oil, [α]D25 = −15.9° (c = 0.13, MeOH). Source: Mangrove-derived fungus Penicillium sp. GQ-7 from mangrove Aegiceras corniculatum (bark, China). Pharm: Cytotoxic (HL60, moderate). Ref: Z. H. Lin, et al, CPB, 2008, 56, 217

3.2 Pyrrolidine Alkaloids

219

6' 7'

O E 6

OH 5

O

N

H

607 Phomasetin Type: 2,4-Pyrrolidinediones. C25H35NO4 Source: Marine-derived fungus Phoma sp. Pharm: Anti-HIV (IC50 = 10 μmol/L). Ref: S. B. Singh, et al, Tet. Lett., 1999, 40, 8775 H

HO

H O

HO N

O

608 Rubroside A Type: 2,4-Pyrrolidinediones. C42H54Cl2N2O16 Amorph. red solid, [α]D24 = −1824° (c = 0.001, MeOH). Source: Lithistid sponge Siliquariaspongia japonica. Pharm: Induces large intracellular vacuoles (rat 3Y1 fibroblasts); cytotoxic (P388, IC50 = 0.046–0.21 μg/mL). Ref: N. U. Sata, et al, JOC, 1999, 64. 2331

Cl

O H

Cl

OH

O

4

N O

O H 2N

O OH

O

OH OH OH

O

O O OH O

609 Rubroside B Type: 2,4-Pyrrolidinediones. C43H54Cl2N2O16 Amorph. red solid, [α]D24 = −1460° (c = 0.001, MeOH). Source: Lithistid sponge Siliquariaspongia japonica. Pharm: Induces large intracellular vacuoles (rat 3Y1 fibroblasts); cytotoxic (P388, IC50 = 0.046–0.21 μg/mL). Ref: N. U. Sata, et al, JOC, 1999, 64. 2331

220

3 Pyrrole Indole and Imidazole Alkaloids

O

Cl

H Cl

OH

O

4

N O

O H2N

O OH

O

OH OH OH

O

O O OH HO

610 Rubroside C Type: 2,4-Pyrrolidinediones. C42H54Cl2N2O16 Amorph. red solid, [α]D24 = −1088° (c = 0.001, MeOH). Source: Lithistid sponge Siliquariaspongia japonica. Pharm: Induces large intracellular vacuoles (rat 3Y1 fibroblasts); cytotoxic (P388, IC50 = 0.046–0.21 μg/mL). Ref: N. U. Sata, et al, JOC, 1999, 64. 2331 H O

Cl

OH

O

4

N O

H Cl

O H 2N

OH OH

O

OH OH

O

O O OH O

611 Rubroside D Type: 2,4-Pyrrolidinediones. C44H56Cl2N2O16 Amorph. red solid, [α]D24 = −1024° (c = 0.001, MeOH). Source: Lithistid sponge Siliquariaspongia japonica. Pharm: Induces large intracellular vacuoles (rat 3Y1 fibroblasts); cytotoxic (P388, IC50 = 0.046–0.21 μg/mL). Ref: N. U. Sata, et al, JOC, 1999, 64. 2331

3.2 Pyrrolidine Alkaloids

221

O

Cl

H Cl

OH

O

4

N O

O H2N

O OH OH OH

O

OH

O

O O OH O

612 Rubroside E Type: 2,4-Pyrrolidinediones. C41H51Cl3N2O16 Amorph. red solid, [α]D24 = −1424° (c = 0.001, MeOH). Source: Lithistid sponge Siliquariaspongia japonica. Pharm: Induces large intracellular vacuoles (rat 3Y1 fibroblasts). Ref: N. U. Sata, et al, JOC, 1999, 64. 2331 Cl

Cl

O

OH

O

4

N O

O

Cl

H2N

O OH OH OH

O

OH

O

O O OH HO

613 Rubroside F Type: 2,4-Pyrrolidinediones. C42H53Cl3N2O16 Amorph. red solid, [α]D24 = −490° (c = 0.001, MeOH). Source: lithistid sponge Siliquariaspongia japonica. Pharm: Induces large intracellular vacuoles (rat 3Y1 fibroblasts). Ref: N. U. Sata, et al, JOC, 1999, 64. 2331 Cl O H Cl

Cl

OH

O

4

N O

O H2N

O OH

O

OH OH OH

O

O O OH O

222

3 Pyrrole Indole and Imidazole Alkaloids

614 Rubroside G Type: 2,4-Pyrrolidinediones. C33H38Cl2N2O9 Amorph. red solid, [α]D24 = −1212° (c = 0.001, MeOH). Source: Lithistid sponge Siliquariaspongia japonica. Pharm: Induces large intracellular vacuoles (rat 3Y1 fibroblasts). Ref: N. U. Sata, et al, JOC, 1999, 64. 2331

O

Cl

H Cl

OH

O

4

N HO

O

O

OH OH

H 2N O

615 Rubroside H Type: 2,4-Pyrrolidinediones. C31H35Cl3N2O9 Amorph. red solid, [α]D24 = −1308° (c = 0.001, MeOH). Source: Lithistid sponge Siliquariaspongia japonica. Pharm: Induces large intracellular vacuoles (rat 3Y1 fibroblasts). Ref: N. U. Sata, et al, JOC, 1999, 64. 2331 Cl

Cl

OH

O

O 4

N HO

O

Cl

O

OH OH

H2N O

616 Streptosetin A Type: 2,4-Pyrrolidinediones. C19H25NO5 Source: Marine-derived streptomycete Streptomyces sp. (sediment, San Francisco Bay). Pharm: Antiplasmodial (Plasmodium falciparum K1, potent); Antituberculosis (Mycobacterium tuberculosis). Ref: T. Amagata, et al, JNP, 2012, 75, 2193│ K. Supong, et al, Phytochem. Lett., 2012, 5, 651 O

O

H

H O

N H

OH

OH

3.2 Pyrrolidine Alkaloids

223

617 Zopfiellamide A Type: 2,4-Pyrrolidinediones. C25H35NO6 Yellowish cryst. (EtOH), mp 225–230 °C, [α]D22 = +5.2° (c = 1.1, CHCl3). Source: Marine-derived fungus Zopfiella latipes CBS 611.97 (fermentations). Pharm: Antibacterial (gram-positive: Arthrobacter citreus, Bacillus brevis, Bacillus subtilis, Bacillus licheniformis, Corynebacterium insidiosum, Micrococcus luteus, Mycobacterium phlei and Streptomyces sp., gram-negative: Acinetobacter calcoaceticus, minimal inhibitory concentrations between 2 and 10 μg/mL); antifungal (yeasts Nematospora coryli and Saccharomyces cerevisiae, minimal inhibitory concentration = 2.0 μg/mL). Ref: M. Daferner, et al, Tetrahedron, 2002, 58, 7781│ M. Saleem, et al, NPR, 2007, 24, 1142 (rev) OH

H

O

N

HO

OH O

O

618 Zopfiellamide B Type: 2,4-Pyrrolidinediones. C26H37NO6 Yellowish oil, [α]D22 = −24° (c = 0.3, CHCl3). Source: Marine-derived fungus Zopfiella latipes CBS 611.97 (fermentations). Pharm: Antifungal (approximately 5 times less active than Zopfiellamide A; yeasts Nematospora coryli and Saccharomyces cerevisiae, minimal inhibitory concentration = 2.0 μg/mL). Ref: M. Daferner, et al, Tetrahedron, 2002, 58, 7781│ M. Saleem, et al, NPR, 2007, 24, 1142–1152 (rev) OH

H

O

N O

HO

OH O

619 Andrimide Type: 2,5-Pyrrolidinediones. C27H33N3O5 Amorph. white solid, mp 172–173.5 °C. Source: Marine bacterium Pseudomonas fluorescens from ascidian Enterobacter sp., marine bacterium Vibrio sp. M22-1 (cultures) from sponge Hyattella sp. (homogenate). Pharm: Antibacterial (in vitro, MRSA, MIC = 4 μg/mL; MRSA, MIC = 2 μg/mL; Staphylococcus aureus (oxacillin resistant), MIC = 8 μg/mL; Staphylococcus aureus (oxacillin, gentamicin, ciprofloxacin resistant), MIC = 2 μg/mL; VREF, MIC = 32 μg/mL; Escherichia coli (permeability mutant), MIC = 2 μg/mL; MREC, MIC = 64 μg/mL). Ref: A. Fredenhagen, et al, JACS. 1987, 109, 4409│ J. Needham, et al, JOC, 1994, 59, 2058│ J. M. Aclarit, et al, Microbios, 1994, 78, 7

224

3 Pyrrole Indole and Imidazole Alkaloids

O O

O N H

H N H

3

O

NH

O

620 3-(2,3-Dibromo-4,5-dihydroxybenzyl)pyrrolidine-2,5-dione Type: 2,5-Pyrrolidinediones. C11H9Br2NO4 Colourless oil. Source: Red alga Rhodomela confervoides (Dalian, Liaoning Province, China). Pharm: Antioxidant (DPPH scavenger, IC50 = (5.22 ± 0.04)μmol/L, control BHT, IC50 = (82.10 ± 0.20)μmol/L); antioxidant (ABTS•+ radical cation scavenger, TEAC = (2.87 ± 0.10)mmol/L, control Ascorbic acid, TEAC = (1.02 ± 0.01)mmol/L). Ref: K. Li, et al, Food Chem., 2012, 135, 868 Br

O

Br NH HO

O

OH

621 Moiramide B Type: 2,5-Pyrrolidinediones. C25H31N3O5 White amorph. solid. Source: Marine bacterium Pseudomonas fluorescens from an unidentified ascidian. Pharm: Antibacterial (in vitro, MRSA, MIC = 2 μg/mL; MRSA, MIC = 0.5 μg/mL; Staphylococcus aureus (oxacillin resistant), MIC = 1 μg/mL; Staphylococcus aureus (oxacillin, gentamicin, ciprofloxacin resistant), MIC = 0.5 μg/mL; VREF, MIC = 4 μg/mL; Escherichia coli (permeability mutant), MIC = 0.25 μg/mL; MREC, MIC = 16 μg/mL). Ref: J. Needham, et al, JOC, 1994, 59, 2058│ D. J. Dixon, et al, Chem. Commun., 1996, 1797│ S. G. Davies, et al, JCS Perken I, 1998, 2635 O O

O

NH N H

N H

O

O

622 Nitrosporeusine A Type: 2,5-Pyrrolidinediones. C14H13NO5S Source: Marine-derived streptomycete Streptomyces nitrosporeus (sediment, Arctic Chukchi Sea). Pharm: Antiviral (inhibits H1N1 virus in infected MDCK cells). Ref: A. Yang, et al, Org. Lett., 2013, 15, 5366

HO

O S O

H N

O H OH

3.2 Pyrrolidine Alkaloids

225

623 Nitrosporeusine B Type: 2,5-Pyrrolidinediones. C14H13NO5S Source: Marine-derived streptomycete Streptomyces nitrosporeus (sediment, Arctic Chukchi Sea). Pharm: Antiviral (inhibits H1N1 virus in infected MDCK cells). Ref: A. Yang, et al, Org. Lett., 2013, 15, 5366

HO

O

H N

O H

S

OH

O

624 Bohemamine Type: Pyrrolizidine alkaloids. C14H18N2O3 Cryst. (CH2Cl2/Et2O), mp 199–200 °C (dec), [α]D25 = 16° (c = 2, MeOH). Source: Marine-derived streptomycete Streptomyces sp. CNQ-583. Pharm: Cell-adhesion inhibitor. Ref: T. S. Bugni, et al, JNP, 2006, 69, 1626 O O N O N H

625 Chlorizidine A Type: Pyrrolizidine alkaloids. C18H10Cl4N2O3 Source: Marine-derived streptomycete Streptomyces sp. (sediment, San Clemente, California, USA). Pharm: Cytotoxic (panel of HTCLs, moderate). Ref: X. Alvarez–Mico, et al, Org. Lett., 2013, 15, 988 OH H

Cl

Cl Cl N

N Cl O

OH

626 Deepoxybohemamine Antibiotic NP 25302 Type: Pyrrolizidine alkaloids. C14H20N2O2 Amorph. solid (CHCl3), mp 229–230 °C, [α] = 115.5° (c = , CHCl3). Source: Marine-derived streptomycete Streptomyces sp. CNQ-583. Pharm: Cell-adhesion inhibitor. Ref: T. S. Bugni, et al, JNP, 2006, 69, 1626

226

3 Pyrrole Indole and Imidazole Alkaloids

O

N O N H

627 (S)-p-Hydroxyphenopyrrozin Type: Pyrrolizidine alkaloids. C13H13NO3 Amorph. solid, [α]D25 = +34° (c = 0.34, MeOH). Source: Deep-sea fungus Chromocleista sp. R721 (seawater-based fermentation, from sediment, Gulf of Mexico). Pharm: Antifungal (yeast Candida albicans, MIC = 25 μg/mL). Ref: Y. C. Park, et al, JNP, 2006, 69, 580 OH

H OH

N O

628 (R)-Phenopyrrozin Type: Pyrrolizidine alkaloids. C13H13NO2 Powder, mp 147–152 °C, [α] = −10.2° (c = 0.6, MeOH). Source: Marine-derived fungus Chromocleista sp. R721. Pharm: Antioxidant (radical scavenger). Ref: Y. C. Park, et al, JNP, 2006, 69, 580

H OH

N O

629 Cyclizidine Antibiotic M 146791 Type: Indolizidine alkaloids. C17H25NO3 Needles (EtOAc), cryst. (Et2O), mp 184 °C, mp 176–178 °C, [α]D23.5 = −46.3° (c = 2, MeOH). Source: Mangrove-derived fungus Saccharopolyspora sp. from an unidentified mangrove (soil, Ishigaki I., Japan). Pharm: Cytotoxic (hmn malignant pleural mesothelioma (MPM) ACC-MESO-1 cells); immunostimulatory. Ref: M. Izumikawa, et al, J. Antibiot., 2012, 65, 41

3.2 Pyrrolidine Alkaloids

O

H N

227

OH OH

630 JBIR 102 Type: Indolizidine alkaloids. C22H33ClO4 Source: Mangrove-derived fungus Saccharopolyspora sp. from an unidentified mangrove (soil, Ishigaki I., Japan). Pharm: Cytotoxic (hmn malignant pleural mesothelioma (MPM) ACC-MESO-1 cells). Ref: M. Izumikawa, et al, J. Antibiot., 2012, 65, 41 O

H N

OH

O

O

H

631 Piclavine B Type: Indolizidine alkaloids. C18H31N Oil, [α]D = +33.5° (c = 1, CH2Cl2). Source: Ascidian Clavelina picta. Pharm: Antimicrobial. Ref: M. F. Raub, et al, Tet. Lett., 1992, 33, 2257 H N

632 Piclavine C Type: Indolizidine alkaloids. C18H29N Pale yellow oil, [α]D = +36° (c = 5, CH2Cl2). Source: Ascidian Clavelina picta. Pharm: Antimicrobial. Ref: M. F. Raub, et al, Tet. Lett., 1992, 33, 2257 H N

633 Stellettamide B Type: Indolizidine alkaloids. C24H41N2O1+ Yellow gum (chloride), [α]D25 = −24.2° (c = 0.5, CHCl3). Source: Sponge Stelletta sp. (Korea Waters). Pharm: Antifungal;

228

3 Pyrrole Indole and Imidazole Alkaloids

cleaves both single- and double-standed RNA. Ref: J. Shin, et al, JNP, 1997, 60, 611│ N. Yamazaki, et al, Org. Lett., 2001, 3, 193 H N

+

N

O

634 Aspochalasin A Type: Cytochalasins. C24H31NO4 Light yellow amorph. powder, [α]D25 = −20° (c = 0.27, CHCl3). Source: Marine-derived fungus Spicaria elegans (varying culture conditions, from sediments, China). Pharm: Cytotoxic (HL60, IC50 = 19.9 μmol/L); antibiotic. Ref: Z. J. Lin, et al, EurJOC, 2009, 3045 O 17 18

O

O O NH H

635 Aspochalasin D Type: Cytochalasins. C24H35NO4 Needles (EtOAc), mp 148 °C (dec), [α]D25 = −81° (c = 1.43, EtOH). Source: Marine-derived fungus Aspergillus elegans from soft coral Sarcophyton sp. (Weizhou coral reef, Giuangxi, China), Marine-derived fungus Spicaria elegans, terrestrial fungi (Aspergillus flavipes and Aspergillus microcysticus). Pharm: Antifoulant (larval settlement of barnacle Balanus Amphitrite, strong); cytotoxic (selective). Ref: W. Keller-Schierlein, et al, Helv. Chim. Acta, 1979, 62, 1501│ T. Tomikawa, et al, J. Antibiot., 2001, 54, 379│ Z. Lin, et al, EurJOC, 2009, 3045│ C. -J. Zheng, et al, Mar. Drugs, 2013, 11, 2054 OH 17 18

OH

O NH H

O

3.2 Pyrrolidine Alkaloids

229

636 Aspochalasin H Type: Cytochalasins. C24H35NO5 Powder, [α]D25 = −107.7° (c = 0.52, CHCl3). Source: Marine-derived fungus Aspergillus elegans from soft coral Sarcophyton sp. (Weizhou coral reef, Giuangxi, China), terrestrial fungus Aspergillus sp. AJ117509. Pharm: Antifoulant (larval settlement of barnacle Balanus Amphitrite, strong). Ref: T. Tomikawa, et al, J. Antibiot., 2001, 54, 379; 2002, 55, 666│ C. -J. Zheng, et al, Mar. Drugs, 2013, 11, 2054 OH 17 18

OH O O O NH

H

637 Aspochalasin I Type: Cytochalasins. C24H35NO5 Solid, mp 136–138 °C, [α]D27 = −166.6° (c = 0.2, CHCl3). Source: Marine-derived fungus Aspergillus elegans from soft coral Sarcophyton sp. (Weizhou coral reef, Giuangxi, China), terrestrial Fungus Aspergillus flavipes. Pharm: Antifoulant (larval settlement of barnacle Balanus Amphitrite, strong); melanogenesis inhibitor. Ref: G. -X. Zhou, et al, JNP, 2004, 67, 328│ S. J. Choo, et al, J. Microbiol. Biotechnol., 2009, 19, 368│ C. -J. Zheng, et al, Mar. Drugs, 2013, 11, 2054 OH OH

17

O

OO NH

H

638 Aspochalasin J Type: Cytochalasins. C24H35NO4 Solid. Source: Marine-derived fungus Aspergillus elegans from soft coral Sarcophyton sp. (Weizhou coral reef, Giuangxi, China), terrestrial Fungus Aspergillus flavipes. Pharm: Antifoulant (larval settlement of barnacle Balanus Amphitrite, strong). Ref: G. -X. Zhou, et al, JNP, 2004, 67, 328│ S. J. Choo, et al, J. Microbiol. Biotechnol., 2009, 19, 368│ C. -J. Zheng, et al, Mar. Drugs, 2013, 11, 2054

230

3 Pyrrole Indole and Imidazole Alkaloids

OH

17

OO

O

NH H

639 Chaetoglobosin A Type: Cytochalasins. C32H36N2O5 Pale yellow prisms (CH2Cl2), mp 188 °C, mp 168– 170 °C, [α]D = −270° (MeOH). Source: Marine-derived fungus Chaetomium sp. (reef, Yap I., Federated States of Micronesia). Pharm: Antifungal; inhibits microtubule assembly. Ref: H. Kobayashi, et al, J. Antibiotics, 1996, 49, 873 OH O 19

20

O O

NH

H N

H O

640 Cytochalasin B2 Type: Cytochalasins. C29H37NO5 Source: Marine-derived fungus Phoma sp. from scyphomedusa (giant jellyfish) Neopilema nomurai (Southern coast of R. O. Korea). Pharm: Cytotoxic (several HTCLs cells). Ref: E. L. Kim, et al, BoMCL, 2012, 22, 3126; 5752

OH H N H

H O O

O

OH

641 Cytochalasin E Type: Cytochalasins. C28H33NO7 mp 206–208 °C (dec), [α]D25 = −25.6° (MeOH). Source: Marine-derived fungus Spicaria elegans, terrestrial fungi (Rosellinia necatrix and Aspergillus clavatus). Pharm: Cytotoxic (MTT method, P388, IC50 = 0.093 μmol/L; A549, IC50 = 0.0062 μmol/L); fibroblast inhibitor, lipid droplet formation inhibitor; cholesteryl ester synthesis inhibitor. Ref: R. Liu, et al, JNP, 2006, 69, 871

3.2 Pyrrolidine Alkaloids

231

OH O O O O

O

H NH

O H

642 Cytochalasin K Type: Cytochalasins. C28H33NO7 Cryst. (hexane/Me2CO), mp 246–248 °C. Source: Marine-derived fungus Spicaria elegans (from sediments, China). Pharm: Cytotoxic (MTT assay, P388, IC50 = 89 μmol/L; A549, IC50 = 8.4 μmol/L); mycotoxin; antibiotic. Ref: P. S. Steyn, et al, JCS Perkin I, 1982, 541│ R. Liu, et al, JNP, 2006, 69, 871 OH

O

O

O O O

H HO 6

NH 5

H

643 Cytochalasin Q Type: Cytochalasins. C30H37NO6 Fine silky needles + 1 Me2CO (Me2CO/petrol), mp 145–147 °C, [α]D23 = −94.5° (c = 1.0, CHCl3) (solvate). Source: Marine-derived fungus Halorosellinia oceanica BCC5149 (Thailand). Pharm: Cytotoxic (KB, IC50 = 3 μg/mL; BC-1, IC50 = 1 μg/mL); antimalarial (Plasmodium falciparum, IC50 = 17 μg/mL). Ref: M. Chinworrungsee, et al, BoMCL, 2001, 11, 1965 O OH O O

H

O

O

NH H

232

3 Pyrrole Indole and Imidazole Alkaloids

644 Cytochalasin Z7 Type: Cytochalasins. C28H35NO5 Needles (MeOH), mp 194–196 °C, [α]D25 = +58.3° (c = 0.08, MeOH). Source: Marine-derived fungus Spicaria elegans (from sediments, China). Pharm: Cytotoxic (MTT assay, P388, IC50 = 75 μmol/L; A549, IC50 = 8.8 μmol/L). Ref: R. Liu, et al, JNP, 2006, 69, 871 OH 17 18

HO

O O

O

H 6

NH 5

H

645 Cytochalasin Z8 Type: Cytochalasins. C28H35NO5 Needles (MeOH), mp 215–217 °C, [α]D25 = +68.2° (c = 0.08, MeOH). Source: Marine-derived fungus Spicaria elegans. Pharm: Cytotoxic (MTT method, P388, IC50 = 56 μmol/L; A549, IC50 = 21 μmol/L). Ref: R. Liu, et al, JNP, 2006, 69, 871 OH 17 18

O

H

O O

HO NH

6 5

H

646 Cytochalasin Z9 Type: Cytochalasins. C28H35NO5 Needles (MeOH), mp 252–254 °C, [α]D25 = +70.4° (c = 0.1, MeOH). Source: Marine-derived fungus Spicaria elegans. Pharm: Cytotoxic (MTT method, P388, IC50 = 99 μmol/L; A549, IC50 = 8.7 μmol/L). Ref: R. Liu, et al, JNP, 2006, 69, 871

3.2 Pyrrolidine Alkaloids

233

OH 17 18

HO

O O

O

H

NH

6 5

H

647 Cytochalasin Z11 Type: Cytochalasins. C25H33NO5 Amorph. solid, [α]D25 = +114.8° (c = 0.08, MeOH). Source: Marine-derived fungus Spicaria elegans (from sediments, China). Pharm: Cytotoxic (A549, moderate). Ref: R. Liu, et al, JNP, 2008, 71, 1127

18

HO

O

17

OH O

HO 6

NH

5

H

648 Cytochalasin Z12 Type: Cytochalasins. C25H35NO5 Amorph. yellow powder, [α]D25 = +43.2° (c = 0.08, MeOH). Source: Marine-derived fungus Spicaria elegans (from sediments, China). Pharm: Cytotoxic (A549, moderate). Ref: R. Liu, et al, JNP, 2008, 71, 1127

18

HO

OH

17

OH O

HO

NH

6 5

H

234

3 Pyrrole Indole and Imidazole Alkaloids

649 Cytochalasin Z16 Type: Cytochalasins. C28H33NO5 Powder (MeOH), [α]D25 = +36.2° (c = 0.1, MeOH). Source: Mangrove-derived fungus Aspergillus flavipes from mangrove Acanthus ilicifolius (China Waters). Pharm: Cytotoxic (A549, IC50 = 19.5 μmol/L, control VP-16, IC50 = 1.03 μmol/L). Ref: Z. -J. Lin, et al, Helv. Chim. Acta, 2009, 92, 1538 O 18 17

O O

O

H 6

O

NH

5

H

650 Cytochalasin Z17 Type: Cytochalasins. C28H33NO5 Powder (MeOH), [α]D25 = +40.8° (c = 0.1, MeOH). Source: Mangrove-derived fungus Aspergillus flavipes from mangrove Acanthus ilicifolius (China Waters). Pharm: Cytotoxic (A549, IC50 = 5.6 μmol/L, control VP-16, IC50 = 1.03 μmol/L). Ref: Z. -J. Lin, et al, Helv. Chim. Acta, 2009, 92, 1538 O 17 18

HO

O

H 6

O O NH

5

H

651 Cytochalasin Z18 Type: Cytochalasins. C31H43NO9 Oil, [α]D25 = +18.8° (c = 0.1, MeOH). Source: Mangrovederived fungus Aspergillus flavipes from mangrove Acanthus ilicifolius (China Waters). Pharm: Cytotoxic (various cencer cells, moderate). Ref: Z. -J. Lin, et al, Helv. Chim. Acta, 2009, 92, 1538

3.2 Pyrrolidine Alkaloids

235

OH O O

O O

H

O O

O

NH

O H

652 Cytochalasin Z19 Type: Cytochalasins. C29H37NO8 Oil, [α]D25 = +28.1° (c = 0.1, MeOH). Source: Mangrove-derived fungus Aspergillus flavipes from mangrove Acanthus ilicifolius. Pharm: Cytotoxic (A549, IC50 = 17.4 μmol/L, control VP-16, IC50 = 1.03 μmol/L). Ref: Z. -J. Lin, et al, Helv. Chim. Acta, 2009, 92, 1538 OH H O

O O

HO

O

H

OO NH

H

653 Cytoglobosin C Type: Cytochalasins. C32H38N2O5 Colorless amorph. powder (DMSO), [α]D25 = +36° (c = 0.02, MeOH). Source: Marine-derived fungus Chaetomium globosum QEN-14 from green alga Ulva pertusa (Qingdao Coast, China). Pharm: Cytotoxic (A549, IC50 = 2.26 μmol/L). Ref: C. -M. Cui, et al, JNP, 2010, 73, 729

OH H

N H

H N H

O O HO HO

236

3 Pyrrole Indole and Imidazole Alkaloids

654 Cytoglobosin D Type: Cytochalasins. C32H38N2O4 Colorless amorph. powder (DMSO), [α]D25 = −34° (c = 0.04, MeOH). Source: Marine-derived fungus Chaetomium globosum QEN-14 from green alga Ulva pertusa (Qingdao Coast, China). Pharm: Cytotoxic (A549, IC50 = 2.55 μmol/L). Ref: C. -M. Cui, et al, JNP, 2010, 73, 729

H

H N H

N H

O O HO HO

655 Deoxaphomin C Type: Cytochalasins. C29H37NO3 Source: Marine-derived fungus Phoma sp. from scyphomedusa (giant jellyfish) Neopilema nomurai (Southern coast of R. O. Korea). Pharm: Cytotoxic (several HTCLs cells). Ref: E. L. Kim, et al, BoMCL, 2012, 22, 3126; 5752

H

N H

H

OH

O O

656 18-Deoxycytochalasin Q Type: Cytochalasins. C30H37NO5 White needles, [α]D25 = −69° (c = 0.72, CHCl3). Source: Marine-derived fungus Xylaria sp. (sediment, South China Sea). Pharm: Cytotoxic (MCF7, SF268 and NCI-H460, all IC50s > 100 μmol/L). Ref: Z. Chen, et al, Helv. Chim. Acta, 2011, 94, 1671 O H

H N H

OO O

H O

657 7-Deoxycytochalasin Z7 Type: Cytochalasins. C28H35NO4 Powder, [α]D25 = +94.8° (c = 0.1, MeOH). Source: Marine-derived fungus Spicaria elegans (treatment by cytochrome P-450 inhibitor

3.2 Pyrrolidine Alkaloids

237

metapyrone, from sediments, China). Pharm: Cytotoxic (MTT assay, A549, IC50 = 15.0 μmol/L). Ref: Z. J. Lin, et al, Can. J. Chem., 2009, 87, 486 OH 17 18

O O

O

H 6

NH

5

H

658 21-Odeacetylcytochalasin Q Type: Cytochalasins. C28H35NO5 White needles, [α]D25 = −66° (c = 0.10, CHCl3). Source: Marine-derived fungus Xylaria sp. (sediment, South China Sea). Pharm: Cytotoxic (MCF7, IC50 > 100 μmol/L, control Cisplatin, IC50 = 2.9 μmol/L; SF268, IC50 = 44.3 μmol/L, Cisplatin, IC50 = 5.3 μmol/L; NCI-H460, IC50 = 96.4 μmol/L, Cisplatin, IC50 = 0.55 μmol/L). Ref: Z. Chen, et al, Helv. Chim. Acta, 2011, 94, 1671 O H

H N H

O OH OH

O

659 Penochalasin A Type: Cytochalasins. C32H35N3O3 Needles (Me2CO), mp 222–224 °C, [α]D = −10° (c = 0.2, CHCl3). Source: Marine-derived fungus Penicillium sp. from green alga Enteromorpha intestinalis. Pharm: Cytotoxic (P388, ED50 = 0.4 μg/mL). Ref: A. Numata, et al, JCS Perkin I, 1996, 239│ C. Iwamoto, et al, Tetrahedron, 1999, 55, 14353

O 20

HN O

21

O 6

NH

5

H NH

238

3 Pyrrole Indole and Imidazole Alkaloids

660 Penochalasin B Type: Cytochalasins. C32H35N3O3 Powder, mp 177–179 °C, [α]D = −6.2° (c = 0.2, CHCl3). Source: Marine-derived fungus Penicillium sp. OUPS-79. Pharm: Cytotoxic (P388, ED50 = 0.3 μg/mL). Ref: A. Numata, et al, JCS Perkin I, 1996, 239

O 20

HN HO

21

O 6

NH

5

H NH

661 Penochalasin C Type: Cytochalasins. C32H35N3O3 Powder, mp 173–178 °C, [α]D = −6.2° (c = 0.1, CHCl3). Source: Marine-derived fungus Penicillium sp. OUPS-79. Pharm: Cytotoxic (P388, ED50 = 0.5 μg/mL). Ref: A. Numata, et al, JCS Perkin I, 1996, 239

O 20

HN

21

HO O 6

NH

5

H NH

662 Penochalasin D Type: Cytochalasins. C32H37N3O3 Colorless oil, [α]D = +10.8° (c = 0.19, CHCl3). Source: Marine-derived fungus Penicillium sp. from green alga Enteromorpha intestinalis. Pharm: Cytotoxic (P388, ED50 = 3.2 μg/mL); HIV-1 protease inhibitor; immunosuppressant. Ref: C. Iwamoto, et al, Tetrahedron, 2001, 57, 2997

3.2 Pyrrolidine Alkaloids

239

O H

N H

HN

N O O

663 Penochalasin E Type: Cytochalasins. C32H38N2O5 Colorless oil, [α]D = −73.0° (c = 0.14, CHCl3). Source: Marine-derived fungus Penicillium sp. from green alga Enteromorpha intestinalis. Pharm: Cytotoxic (P388, ED50 = 2.1 μg/mL); HIV-1 protease inhibitor; immunosuppressant. Ref: C. Iwamoto, et al, Tetrahedron, 2001, 57, 2997 O H

H

N H

HN O O O

HO

H

664 Penochalasin F Type: Cytochalasins. C32H38N2O5 Colorless oil, [α]D = −80.0° (c = 0.13, CHCl3). Source: Marine-derived fungus Penicillium sp. from green alga Enteromorpha intestinalis. Pharm: Cytotoxic (P388, ED50 = 1.8 μg/mL); HIV-1 protease inhibitor; immunosuppressant. Ref: C. Iwamoto, et al, Tetrahedron, 2001, 57, 2997 O H

H

N H

HN O O O

H

OH

665 Penochalasin G Type: Cytochalasins. C32H38N2O4 Colorless powder, mp 124–126 °C, [α]D = −143.6° (c = 0.19, CHCl3). Source: Marine-derived fungus Penicillium sp. from green alga Enteromorpha intestinalis. Pharm: Cytotoxic (P388, ED50 = 1.9 μg/mL); HIV-1 protease inhibitor; immunosuppressant. Ref: C. Iwamoto, et al, Tetrahedron, 2001, 57, 2997

240

3 Pyrrole Indole and Imidazole Alkaloids

H

H

N H

HN O O O

OH

666 Penochalasin H Type: Cytochalasins. C32H38N2O5 Colorless powder, mp 180–182 °C, [α]D = −72.7° (c = 0.18, CHCl3). Source: Marine-derived fungus Penicillium sp. from green alga Enteromorpha intestinalis. Pharm: Cytotoxic (P388, ED50 = 2.8 μg/mL); HIV-1 protease inhibitor; immunosuppressant. Ref: C. Iwamoto, et al, Tetrahedron, 2001, 57, 2997

OH H

N H

H

HN O O O

OH

667 Rosellichalasin Type: Cytochalasins. C28H33NO5 Source: Mangrove-derived fungus Aspergillus flavipes from mangrove Acanthus ilicifolius. Pharm: Cytotoxic (A549, IC50 = 5.6 μmol/L, control VP-16, IC50 = 1.03 μmol/L). Ref: Z. -J. Lin, et al, Helv. Chim. Acta, 2009, 92, 1538│ Y. Kimura, et al, Agric. Biol. Chem., 1989, 53, 1699 O

H

O

OO NH

O H

668 Xylarisin Xylarisin A Type: Cytochalasins. C22H33NO5 Cryst., mp 210–212 °C, [α]D24 = −88.7° (c = 0.1, CHCl3). Source: Marine-derived fungus Xylaria sp. PSU-F100 from gorgonian sea fan Annella sp. (Similan Is., Thailand). Pharm: Antibacterial (Staphylococcus aureus and MRSA, mild). Ref: V. Rukachaisirikul, et al, CPB, 2009, 57, 1409

3.3 Indole Alkaloids

241

OH

O H O H O

N H

OH

3.3 Indole Alkaloids 669 N-{1-[4-(Acetylamino)phenyl]-3-hydroxy-1-(1H-indol-3-yl)propan-2-yl}2,2-dichloroacetamide Type: Indole alkaloids. C21H21Cl2N3O3 Source: Deep-sea sediment metagenomic clone-derived bacterium Escherichia coli (fermentation broth). Pharm: Analgetic. Ref: L. Chen, et al, J. Asian. Nat. Prod. Res., 2011, 13, 444 O

H N O H N

Cl Cl

HO N H

670 6-Bromo-4,5-dihydroxyindole Type: Indole alkaloids. C8H6BrNO2 Amorph. solid. Source: Prosobranch Drupella fragum (mid-intestinal gland, Japan). Pharm: Antioxidant (POV Peroxide value method, POVsample/POVcontrol = 0.194 mequiv/kg, control α-Tocopherol, POVsample/ POVcontrol = 0.062 mequiv/kg, Butylated hydroxytolune (BHT), POVsample/POVcontrol = 0.031 mequiv/kg). Ref: M. Ochi, et al, JNP, 1998, 61, 1043 OH HO Br

N H

671 6-Bromo-4,7-dihydroxyindole Type: Indole alkaloids. C8H6BrNO2 Amorph. solid. Source: Prosobranch Drupella fragum (mid-intestinal gland, Japan). Pharm: Antioxidant (POV Peroxide value method, POVsample/POVcontrol = 0.106 mequiv/kg, control α-Tocopherol, POVsample/ POVcontrol = 0.062 mequiv/kg, Butylated hydroxytolune (BHT), POVsample/POVcontrol = 0.031 mequiv/kg). Ref: M. Ochi, et al, JNP, 1998, 61, 1043

242

3 Pyrrole Indole and Imidazole Alkaloids

OH

N H

Br OH

672 6-Bromo-5-hydroxy-1H-indole Type: Indole alkaloids. C8H6BrNO Amorph. solid. Source: Prosobranch Drupella fragum (mid-intestinal gland, Japan). Pharm: Antioxidant (POV Peroxide value method, POVsample/POVcontrol = 0.036 mequiv/kg, control α-Tocopherol, POVsample/ POVcontrol = 0.062 mequiv/kg, Butylated hydroxytolune (BHT), POVsample/POVcontrol = 0.031 mequiv/kg). Ref: M. Ochi, et al, JNP, 1998, 61, 1043 HO

N H

Br

673 6-Bromoindole-3-carbaldehyde Type: Indole alkaloids. C9H6BrNO Solid (MeOH), mp 203–204 °C. Source: Sponges Pseudosuberites hyalinus and Rhopaloeides odorabile. Pharm: PLA2 inhibitor (bee venom PLA2, IC50 = (1.27 ± 0.06)mmol/L); antibacterial; antifoulant; plant growth regulator; algicide. Ref: A. Longeon, et al, Mar. Drugs, 2011, 9, 879│ T. Rasmussen, et al, JNP, 1993, 56, 1553│ G. Olguin-Uribe, et al, J. Chem. Ecol., 1997, 23, 2507 O

H

N H

Br

674 6-Bromo-1H-indole-3-carboxylic acid methyl ester Type: Indole alkaloids. C10H8BrNO2 Yellow solid. Source: Sponges Thorectandra sp. (NCI, Developmental Therapeutics Program) and Smenospongia sp. (Uni. of California, Santa Cruz). Pharm: Antibacterial (Staphylococcus epidermidis, weak). Ref: N. L. Segraves, et al, JNP, 2005, 68, 1484 O

Br

N H

O

3.3 Indole Alkaloids

243

675 3-Chloro-1H-indole Type: Indole alkaloids. C8H6ClN mp 95.5–96 °C. Source: Hemichordate acorn worm Ptychodera flava laysanica. Pharm: Principal odorous component of marine hemichordate Ptychodera flava laysanica. Ref: T. Higa, et al, Naturwissenschaften, 1975, 62, 395 Cl N H

676 Convalutamydine A Type: Indole alkaloids. C11H9Br2NO3 Amorph. solid (MeOH), mp 190–195 °C, [α]D26 = +27.4° (C = 0.06, MeOH). Source: Bryozoan Amathia convoluta (Gulf of Mexico coast of Florida). Pharm: Cytotoxic (differentiation of HL60; induces change of characteristics of the differentiation, such as growth arrest, adhesiveness to culture plate, phagocytosis of latex particles, 0.1–25 μg/mL) Ref: Y. Kamano. et al, Tet. Lett., 1995, 36. 2783│ H. Zhang, et al, Tetrahedron, 1995, 51, 5523│ G. K. Jnaneshwara, et al, J. Chem. Res. (S), 1999, 632│ G. K. Jnaneshwara, et al, Synth. Comm., 1999, 29, 3627 Br

Br

HO

N H

O

O

677 Convolutamydine B Type: Indole alkaloids. C10H8Br2ClNO2 Amorph. solid (Me2CO), mp 225–227 °C, [α]D25 = +18.1° (c = 0.04, MeOH). Source: Bryozoan Amathia convoluta (Gulf of Mexico coast of Florida). Pharm: Cytotoxic (HL60, cellular differentiation inducer). Ref: Y. Kamano, et al, Tet. Lett., 1995, 36, 2783│ H. Zhang, et al, Tetrahedron, 1995, 51, 5523 Cl Br OH O Br

N H

678 Convolutamydine C Type: Indole alkaloids. C9H7Br2NO2 Amorph. solid (Me2CO), mp 175–180 °C, [α]D25 = +32.4° (c = 0.03, MeOH). Source: Bryozoan Amathia convoluta (Gulf of Mexico coast of Florida). Pharm: Cytotoxic (HL60, cellular differentiation inducer). Ref: Y. Kamano, et al, Tet. Lett., 1995, 36, 2783│ H. Zhang, et al, Tetrahedron, 1995, 51, 5523

244

3 Pyrrole Indole and Imidazole Alkaloids

Br OH O N H

Br

679 Convolutamydine D Type: Indole alkaloids. C10H7Br2NO2 Amorph. solid, [α]D26 = +14.0° (c = 0.04, MeOH). Source: Bryozoan Amathia convoluta (Gulf of Mexico coast of Florida). Pharm: Cytotoxic (exhibits potent activity in the differentiation of HL60 cells). Ref: Y. Kamano, et al, Tet. Lett., 1995, 36, 2783│ H. Zhang, et al, Tetrahedron, 1995, 51, 5523 Br OH O N H

Br

680 3,6-Dibromo-1H-indole Type: Indole alkaloids. C8H5Br2N Oil. Source: Hemichordate acorn worms Ptychodera flava and Glossobalanus sp., ascidian Distaplia regina (Palau, Oceania). Pharm: Antibacterial. Ref: A. Qureshi, et al, Nat Prod. Lett., 1999, 13. 59│ T. Higa, et al, Comp. Biochem. PhysioL, B, 1980, 65, 525 Br

N H

Br

681 Granulatamide A Type: Indole alkaloids. C23H34N2O Source: Soft coral Eunicella granulata. Pharm: Cytotoxic (DU145, LNCaP, SK-OV-3, IGROV, IGROV-ET, SKBR3, SK-MEL-28, HMEC1, A549, K562, PANC1, HT29, LoVo, LoVo-DOX, HeLa and HeLa-APL, GI50 = 1.7– 13.8 μmol/L). Ref: F. Reyes, et al, JNP, 2006, 69, 668 H N N H

O

682 Granulatamide B Type: Indole alkaloids. C24H34N2O Source: Soft coral Eunicella granulata. Pharm: Cytotoxic (DU145, LNCaP, SK-OV-3, IGROV, IGROV-ET, SKBR3, SK-MEL-28, HMEC1, A549, K562, PANC1, HT29, LoVo, LoVo-DOX, HeLa and HeLa-APL, GI50 = 1.7– 13.8 μmol/L). Ref: F. Reyes, et al, JNP, 2006, 69, 668

3.3 Indole Alkaloids

245

H N O

N H

683 Hainanerectamine B Type: Indole alkaloids. C12H11NO2 Source: Sponge Hyrtios erectus (Hainan). Pharm: Inhibitor of serine/threonine kinase Aurora A (IC50 = 24.5 μg/mL, involved in cell division regulation). Ref: W. -F. He, et al, Mar. Drugs, 2014, 12, 3982 HO

H

O

H

N H

684 (–)-Herbindole A Type: Indole alkaloids. C15H19N Needles (MeOH), mp 120–122 °C. Source: Sponge Axinella sp. (Australia). Pharm: Cytotoxic; antifeedant (fish). Ref: H. Muratake, et al, CPB, 1994, 42, 854

N H

685 (+)-Herbindole A Type: Indole alkaloids. C15H19N Colorless needles, mp 134–136 °C, [α]D21 = +56.9° (c = 0.28, CHCl3). Source: Sponge Axinella sp. (Australia). Pharm: Cytotoxic. Ref: R. Herb, et al, Tetrahedron, 1990, 46, 3089│ H. Muratake, et al, Tet. Lett., 1992, 33, 4595

N H

686 (–)-Herbindole B Type: Indole alkaloids. C16H21N Needles (MeOH), mp 118–120 °C. Source: Sponge Axinella sp. (Australia). Pharm: Cytotoxic; antifeedant (fish). Ref: H. Muratake, et al, CPB, 1994, 42, 854

246

3 Pyrrole Indole and Imidazole Alkaloids

N H

687 (+)-Herbindole B Type: Indole alkaloids. C16H21N Colorless needles, mp 131–133 °C, [α]D21 = +51.2° (c = 0.26, CHCl3). Source: Sponge Axinella sp. (Australia). Pharm: Cytotoxic. Ref: R. Herb, et al, Tetrahedron, 1990, 46, 3089│ H. Muratake, et al, Tet. Lett., 1992, 33, 4595

N H

688 (–)-Herbindole C Type: Indole alkaloids. C18H23N Oil. Source: Sponge Axinella sp. (Australia). Pharm: Cytotoxic; antifeedant (fish). Ref: H. Muratake, et al, CPB, 1994, 42, 854

N H

689 (+)-Herbindole C Type: Indole alkaloids. C18H23N Colorless syrup, [α]D22 = +19.9° (c = 0.18, CHCl3). Source: Sponge Axinella sp. (Australia). Pharm: Cytotoxic. Ref: R. Herb, et al, Tetrahedron, 1990, 46, 3089│ H. Muratake, et al, Tet. Lett., 1992, 33, 4595

N

3.3 Indole Alkaloids

247

690 Herdmanine E Type: Indole alkaloids. C22H28BrN5O6 Ascidian Herdmania momus. Source: Ascidian Herdmania momus. Pharm: Peroxisome proliferator-activated receptor (PPAR)-γ agonistic activity. Ref: J. L. Li, et al, JNP, 2012, 75, 2082

O

OH

O

H N

HO N H

O Br O

NH2

R

NH

N H

691 Herdmanine I Type: Indole alkaloids. C15H20N4O4 Source: Ascidian Herdmania momus (Jeju I., S. Korea). Pharm: Peroxisome proliferator-activated receptor (PPAR)-γ agonistic activity (cell-based luciferase reporter assay). Ref: J. L. Li, et al, JNP, 2012, 75, 2082; 2013, 76, 815 O N H

HO N H

H N

O

HO NH2

692 Herdmanine J Type: Indole alkaloids. C15H21N3O3 Source: Ascidian Herdmania momus (Jeju I., S. Korea). Pharm: Peroxisome proliferator-activated receptor (PPAR)-γ agonistic activity (cell-based luciferase reporter assay). Ref: J. L. Li, et al, JNP, 2012, 75, 2082; 2013, 76, 815 O N H N HOOC

NH2

693 Herdmanine K Type: Indole alkaloids. C16H14N4O5 Source: Ascidian Herdmania momus (Jeju I., S. Korea). Pharm: Peroxisome proliferator-activated receptor (PPAR)-γ agonistic activity (cell-based luciferase reporter assay). Ref: J. L. Li, et al, JNP, 2012, 75, 2082│J. L. Li, et al, JNP, 2013, 76, 815

248

3 Pyrrole Indole and Imidazole Alkaloids

O HO

H N O

N H

N COOH

N H

694 Herdmanine L Type: Indole alkaloids. C16H15NO5 Source: Ascidian Herdmania momus (Jeju I., S. Korea). Pharm: Peroxisome proliferator-activated receptor (PPAR)-γ agonistic activity (cell-based luciferase reporter assay). Ref: J. L. Li, et al, JNP, 2012, 75, 2082; 2013, 76, 815 NH2

O

COOH

O HO

695 Hicksoane A Type: Indole alkaloids. C23H30INO2 Pale yellow powder, [α]D20 = +31° (c = 0.01, MeOH). Source: Gorgonian Subergorgia hicksoni. Pharm: Antifouling. Ref: T. Řezanka, et al, EurJOC, 2008, 2008, 1265 O H

H

O N H

I

696 Hicksoane B Type: Indole alkaloids. C23H30INO2 Pale yellow powder, [α]D20 = +37° (c = 0.009, MeOH). Source: Gorgonian Subergorgia hicksoni. Pharm: Antifouling. Ref: T. Řezanka, et al, EurJOC, 2008, 2008, 1265

I

O H

H

O N H

3.3 Indole Alkaloids

249

697 Hicksoane C Type: Indole alkaloids. C23H29I2NO2 Yellow powder, [α]D20 = +41° (c = 0.007, MeOH). Source: Gorgonian Subergorgia hicksoni. Pharm: Antifouling. Ref: T. Řezanka, et al, EurJOC, 2008, 2008, 1265

O H

I

H

O N H

I

698 3-(Hydroxyacetyl)-1H-indole Type: Indole alkaloids. C10H9NO2 Source: Sponge Tedania ignis. Pharm: Plant growth regulator; CNS stimulant. Ref: R. L. Dillman, et al, JNP, 1991, 54, 1056 O OH

5

N H

699 3-(2-Hydroxyethyl)-6-prenylindole Type: Indole alkaloids. C15H19NO Source: Marine-derived streptomycete Streptomyces sp. BL-49-58-005. Pharm: Cytotoxic (panel of 14 different tumor cell lines; K562, GI50 = 8.46 μmol/L). Ref: J. M. Sánchez López, et al, JNP, 2003, 66, 863 OH

N H

700 1H-Indole-3-carboxylic acid methyl ester Type: Indole alkaloids. C10H9NO2 mp 147–148 °C, mp 140 °C. Source: Sponge Spongosorites sp. Pharm: Cytotoxic (several hmn cancer cell lines, weak). Ref: B. Bao, et al, Mar. Drugs, 2007, 5, 31 O

N H

O

250

3 Pyrrole Indole and Imidazole Alkaloids

701 2-(1H-Indol-3-yl)ethyl-5-hydroxypentanoate Type: Indole alkaloids. C15H19NO3 Oil. Source: Marine-derived fungus Pichia membranifaciens USF-HO-25 from sponge Halichondria okadai (Japan waters). Pharm: Antioxidant (DPPH scavenger, weak). Ref: Y. Sugiyama, et al, JNP, 2009, 72, 2069 O OH

O

N H

702 2-(1H-Indol-3-yl)ethyl-2-hydroxypropanoate Type: Indole alkaloids. C13H15NO3 Oil. Source: Marine-derived fungus Pichia membranifaciens USF-HO-25 from sponge Halichondria okadai (Japan waters). Pharm: Antioxidant (DPPH scavenger, weak). Ref: Y. Sugiyama, et al, JNP, 2009, 72, 2069 O O OH N H

703 3-Indolylglyoxylic acid Type: Indole alkaloids. C10H7NO3 Source: Ascidian Polyandrocarpa zorritensis (Bay of Taranto, Mediterranean Sea). Pharm: Cytotoxic (C6, IC50 = (314 ± 17)μmol/L; HeLa and H9c2, inactive). Ref: A. Aiello, et al, Mar. Drugs, 2011, 9, 1157 O

OH O

N H

704 3-Indolylglyoxylic acid methyl ester α-Oxo-1H-indole-3-acetic acid methyl ester Type: Indole alkaloids. C11H9NO3 Grey cryst. +1AcOH (AcOH), mp 211 °C. Source: Sponge Spongosorites sp., ascidian Polyandrocarpa zorritensis (Bay of Taranto, Mediterranean Sea). Pharm: Cytotoxic (C6, IC50 = (305 ± 15)μmol/L; HeLa and H9c2, inactive). Ref: B. Bao, et al, Mar. Drugs, 2007, 5, 31│ A. Aiello, et al, Mar. Drugs, 2011, 9, 1157

3.3 Indole Alkaloids

O

251

O O

N H

705 6-(1H-Indol-3-yl)-5-methyl-3,5-heptadien-2-one Type: Indole alkaloids. C16H17NO Source: Sponge Tedania ignis. Pharm: Phytotoxic. Ref: R. L. Dillman, et al, JNP, 1991, 54, 1056

O N H

706 (1H-Indol-3-yl) oxoacetic acid methyl ester Type: Indole alkaloids. C11H7Br2NO3 Source: Sponges Spongosorites sp. (off coast of Jeju I., R. O. Korea) and Rhopaloeides odorabile. Pharm: PLA2 inhibitor (bee venom PLA2, IC50 = (1.11 ± 0.33)mmol/L). Ref: A. Longeon, et al, Mar. Drugs, 2011, 9, 879│ B. Bao,et al, Mar. Drugs, 2007, 5, 31 O

O

O

Br Br

N H

707 Iso-trans-trikentrin B Type: Indole alkaloids. C17H21N Source: Sponge Trikentrion flabelliforme. Pharm: Antimicrobial. Ref: R. J. Capon, et al, Tetrahedron, 1986, 42, 6545│ H. Muratake, et al, CPB, 1994, 42, 854│ J. K. MacLeod, et al, Aust. J. Chem., 1998, 51, 177

N H

708 5-Methoxy-1H-indole-4,7-dione Type: Indole alkaloids. C9H7NO3 Orange needles, mp 198–200 °C. Source: Prosobranch Drupella fragum (mid-intestinal gland, Japan). Pharm: Antibacterial

252

3 Pyrrole Indole and Imidazole Alkaloids

(Staphylococcus aureus, Bacillus subtilis and Escherichia coli, MIC = 6.25–50 μg/mL). Ref: Y. Fukuyama, et al, Tetrahedron, 1998, 54, 10007 O O N H O

709 6-Methoxy-1H-indole-4,7-dione Type: Indole alkaloids. C9H7NO3 Orange prisms, mp 188–190 °C. Source: Prosobranch Drupella fragum (mid-intestinal gland, Japan). Pharm: Antibacterial (Staphylococcus aureus, Bacillus subtilis and Escherichia coli, MIC = 6.25–50 μg/mL). Ref: Y. Fukuyama, et al, Tetrahedron, 1998, 54, 10007 O

N H

O O

710 1-Methyl indole-3-carboxamide Type: Indole alkaloids. C10H10N2O Source: Marine actinomycete Actinomadura sp. BCC 24717. Pharm: Antifungal (Candida albicans, IC50 = 41.97 μg/mL). Ref: J. Kornsakulkarn, Phytochem. Lett., 2013, 6, 491 O

NH2

N

711 5-Methyl-1H-indole-4,7-dione Type: Indole alkaloids. C9H7NO2 Orange prisms, mp 202–204 °C. Source: Prosobranch Drupella fragum (mid-intestinal gland, Japan). Pharm: Antibacterial (Staphylococcus aureus, Bacillus subtilis and Escherichia coli, MIC = 6.25–50 μg/mL). Ref: Y. Fukuyama, et al, Tetrahedron, 1998, 54, 10007 O

N H O

3.3 Indole Alkaloids

253

712 3-((6-Methylpyrazin-2-yl)methyl)-1H-indole Type: Indole alkaloids. C14H13N3 Source: Deep-sea actinomycete Serinicoccus profundi sp. nov. Pharm: Antibacterial (Staphylococcus aureus ATCC 25923, weak). Ref: X. -W. Yang, et al, Mar. Drugs, 2012, 11, 33 N N

N H

713 1-Methyl-2,3,5-tribromoindole Type: Indole alkaloids. C9H6Br3N mp 120–122 °C. Source: Red alga Laurencia sp. (N. Borneo I., Sabah, Malaysia), red alga Laurencia brongniartii, sea hare Aplysia dactylomela. Pharm: Antibacterial (30mg/disc: Staphylococcus sp., IZD = 9 mm, MIC = 300 μg/mL); cytotoxic (PS, ED50 = 47 μg/mL). Ref: C. S. Vairappan, et al, Mar. Drugs, 2010, 8, 1743│ G. T. Carter, et al, Tet. Lett., 1978, 4479│ F. J. Schmitz, et al, JACS, 1982, 104, 6415 Br Br Br N

714 Penipaline C Type: Indole alkaloids. C14H15NO2 Source: Deep-sea fungus Penicillium paneum SD-44 (sediment, cultivated in a 500 L bioreactor). Pharm: Cytotoxic (A549, IC50 = 20.4–21.5 μmol/L; HCT116, IC50 = 14.9–18.5 μmol/L for five compounds from the paper). Ref: C. Li, et al, Helv. Chim. Acta, 2014, 97, 1440 O H HO

N H

715 2,3,5,6-Tetrabromo-1H-indole Type: Indole alkaloids. C8H3Br4N mp 152.5–154 °C, mp 149–151 °C. Source: Red alga Laurencia brongniartii. Pharm: Antibacterial. Ref: G. T. Carter, et al, Tet. Lett., 1978, 4479 Br Br Br Br

N H

254

3 Pyrrole Indole and Imidazole Alkaloids

716 2,3,5,6-Tetrabromo-1-methyl-1H-indole Type: Indole alkaloids. C9H5Br4N Cryst. (petroleum ether), mp 171.5–172 °C, mp 168–170 °C. Source: Red alga Laurencia brongniartii. Pharm: Antibacterial. Ref: G. T. Carter, et al, Tet. Lett., 1978, 4479 Br Br Br N

Br

717 2,5,6-Tribromo-N-methylgramine Type: Indole alkaloids. C12H13Br3N2 Source: Bryozoan Zoobotryon verticillatum. Pharm: Cell division Inhibitor (fertilized urchin egg assay). Ref: A. Sato, et al, Tet. Lett., 1983, 24, 481 N Br Br

N

Br

718 2,5,6-Tribromo-N-methylgramine N-oxide Type: Indole alkaloids. C12H13Br3N2O Cryst. (MeOH aq), mp 116–120 °C (dec), Sol. MeOH, EtOAc; poorly sol. H2O. Source: Bryozoan Zoobotryon verticillatum. Pharm: Toxic (brine shrimp). Ref: A. Sato, et al, Tet. Lett., 1983, 24, 481 O N

+

Br Br

N

Br

719 2,3,6-Tribromo-1-methyl-1H-indole Type: Indole alkaloids. C9H6Br3N mp 90.5–91 °C. Source: Red alga Laurencia brongniartii. Pharm: Antibacterial. Ref: G. T. Carter, et al, Tet. Lett., 1978, 4479 Br 5

4

6 7

Br

3 1

2

Br

N

720 (1′′S,3′′S)-Trikentrin A Type: Indole alkaloids. C15H19N Stable oil which cryst. on standing, [α]D = +23.3° (c = 1.0, CHCl3). Source: Sponge Trikentrion flabelliforme. Pharm: Antimicrobial.

3.3 Indole Alkaloids

255

Ref: R. J. Capon, et al, Tetrahedron, 1986, 42, 6545│ H. Muratake, et al, CPB, 1994, 42, 854

1''

N H 3''

721 (1′′R,3′′S)-Trikentrin A Type: Indole alkaloids. C15H19N Unstable oil, [α]D = +4.8° (c = 2.47, CHCl3). Source: Sponge Trikentrion flabelliforme. Pharm: Antimicrobial. Ref: R. J. Capon, et al, Tetrahedron, 1986, 42, 6545│ H. Muratake, et al, CPB, 1994, 42, 854

1''

N H 3''

722 cis-Trikentrin B Type: Indole alkaloids. C17H21N mp 57–58 °C, [α]D = +48° (c = 2.47, CHCl3). Source: Sponge Trikentrion flabelliforme. Pharm: Antimicrobial. Ref: R. J. Capon, et al, Tetrahedron, 1986, 42, 6545│ E. Fahy, et al, Tet. Lett., 1988, 29, 3427│ H. Muratake, et al, CPB, 1994, 42, 854│ H. Muratake, et al, Tet. Lett., 1993, 34, 4815

N H

723 Tryptophol Type: Indole alkaloids. C10H11NO Prisms (C6H6/petrol); plates (Et2O/petrol), mp 59 °C, bp2mmHg 174 °C. Source: Sponge Luffariella geometrica, terrestrial fungi (Drechslera nodulosum and Acremonium lolii). Pharm: Antibacterial (gram-positive bacteria); antifungal (Candida albicans); plant auxin; LD50 (mus, ipr) 351 mg/kg. Ref: F. Sugawara, et al, Phytochemistry 1987, 26, 1349│ P. G. Mantle,et al, Phytochemistry 1994, 36, 1209│ S. Kehraus, et al, JNP, 2002, 65, 1056

256

3 Pyrrole Indole and Imidazole Alkaloids

OH

N H

3.4 Bisindole Alkaloids 724 Arsindoline B Type: Bisindole alkaloids. C22H22N2O2 Amorph. powder. Source: Marine-derived bacterium Aeromonas sp. CB101 (Xiamen Sea, China). Pharm: Cytotoxic (A549, IC50 = 22.6 μmol/L). Ref: S. -X. Cai, et al, Helv. Chim. Acta, 2010, 93, 791 O O N H

N H

725 3,3′-Bis(4,6-dibromo-2-methylsulfinyl)indole Type: Bisindole alkaloids. C18H12Br4N2O2S2 Source: Red alga Laurencia brongniartii (Taiwan). Pharm: Cytotoxic (HT29, P388). Ref: A. A. El-Gamal, et al, JNP, 2005, 68, 815 H N Br

Br

S O

O S

Br

N H

Br

726 7,7-Bis(3-indolyl)-p-cresol 4-[(Di-1H-indol-3-yl)methyl]phenol Type: Bisindole alkaloids. C23H18N2O Gum. Source: Marine bacterium Vibrio sp. from sponge Hyattella sp. Pharm: Antimicrobial. Ref: J. M. Oclarit, et al, Nat. Prod. Lett., 1994, 4, 309 OH

N H

N H

3.4 Bisindole Alkaloids

257

727 3,3′-Bis(2′-methylsulfinyl-2-methylthio-4,6,4′,6′-tetrabromo)indole Type: Bisindole alkaloids. C18H12Br4N2OS2 Source: Red alga Laurencia brongniartii (Taiwan). Pharm: Cytotoxic (HT29, P388). Ref: A. A. El-Gamal, et al, JNP, 2005, 68, 815 H N Br

Br

S O Br

S N H

Br

728 Caulerchlorin Type: Bisindole alkaloids. C22H15ClN2O2 Source: Green alga Caulerpa racemosa (China Waters). Pharm: Antifungal (Cryptococcus neoformans 32609, MIC80 = 16 μg/ mL). Ref: D. -Q. Liu, et al, Heterocycles, 2012, 85, 661 O O

N H

N H Cl

729 Caulerpin Type: Bisindole alkaloids. C24H18N2O4 Red prisms or needles (Et2O or Me2CO), mp 317 °C. Source: Green algae Caulerpa serrulata, Caulerpa racemosa, Caulerpa sertularioides, Caulerpa taxifolia, Caulerpa cuppresoides, Caulerpa scalpelliformis and Caloglossa leprieurii, red alga Laurencia majuscule. Pharm: Plant growth regulator; phycotoxin, vermifuge. Ref: B. C. Maiti, et al, J. Chem. Res. (S), 1978, 126│ J. G. Schwede, et al, Phytochemistry, 1987, 26, 155│ M. B. Govenkar, et al, Phytochemistry, 2000, 54, 979│ E. T. De Souza, et al, Mar. Drugs, 2009, 7, 689 O

O

H N N H O

O

730 Chloro-bisindole Type: Bisindole alkaloids. C22H15ClN2O2 Source: Green alga Caulerpa racemosa (Zhanjiang coastline, China). Pharm: Antifungal (weak). Ref: D. -Q. Liu, et al, Heterocycles, 2012, 85, 661

258

3 Pyrrole Indole and Imidazole Alkaloids

O O H N N H Cl

731 Chondriamide A Type: Bisindole alkaloids. C21H17N3O Yellow cryst. (MeOH aq), mp 193–194 °C. Source: Red alga Chondria sp. (Argentina). Pharm: Cytotoxic (KB, 0.5 μg/mL; LoVo, 10 μg/mL); antiviral (HSV-2, 1 μg/mL); anthelmintic. Ref: J. A. Palermo, et al, Tet. Lett., 1992, 33, 3097 H N

O N H 7

10'

N H

732 Chondriamide B Type: Bisindole alkaloids. C21H17N3O2 Yellow cryst. (MeOH aq), mp 208–209 °C. Source: Red alga Chondria sp. (Argentina). Pharm: Antifungal (Aspergillus oryzae, IZD = 6 mm at 250 μg/disk; Tricdhophyton mentagrophytes, IZD = 11 mm at 250 μg/ disk). Ref: J. A. Palermo, et al, Tet. Lett., 1992, 33, 3097 H N

O N H

7

OH

N H

733 Chondriamide C Type: Bisindole alkaloids. C21H17N3O Yellow powder, mp 230.5–232.0 °C. Source: Red alga Chondria atropurpurea. Pharm: Anthelmintic (EC80 = 0.09 mmol/L). Ref: D. Davyt, et al, JNP, 1998, 61, 1560 O 10'Z

N H N H

N H

3.4 Bisindole Alkaloids

259

734 Citorellamine Type: Bisindole alkaloids. C22H24Br2N4S Needles (MeOH), mp 210 °C (dec). Source: Ascidian Polycitorella mariae. Pharm: Cytotoxic; antimicrobial (potent). Ref: R. M. Moriarty, et al, Tet. Lett., 1987, 28, 749 NH Br

H N

S

N H

Br

HN

735 Dendridine A Type: Bisindole alkaloids. C20H20Br2N4O2 Yellowish solid. Source: Sponge Dictyodendrilla sp. Pharm: Antibacterial (Bacillus subtilis, MIC = 8.3 μg/mL, Micrococcus luteus, MIC = 4.2 μg/mL); antifungal (Cryptococcus neoformans, MIC = 8.3 μg/mL); cytotoxic (L1210, IC50 = 32.5 μg/mL). Ref: M. Tsuda, et al, JNP, 2005, 68, 1277 OH

H N

Br

NH2

Br

NH2 N OH

H

736 Dihydrodeoxybromotopsentin Spongotine B Type: Bisindole alkaloids. C20H15BrN4O Amorph. yellow powder, [α]D24 = +198° (c = 2.0, MeOH). Source: Sponges Spongosorites sp., Topsentia sp. and Rhaphisia lacazei. Pharm: Antiviral; antineoplastic. Ref: B. Bao, et al, JNP, 2005, 68, 711; 2007, 70, 2 O

21

N 6

Br

HN N H

12

13

NH 14

737 2,2-Di-3-indolyl-3-indolone 2,2-Bis(3-indolyl)indoxyl Type: Bisindole alkaloids. C24H17N3O Oil. Source: Marine bacterium Vibrio parahaemolyticus from boxfish Ostracion cubicus (toxic mucus). Pharm: Antibacterial. Ref: Y. H. Loo, et al, Chem. Ind. (London), 1957, 1123

260

3 Pyrrole Indole and Imidazole Alkaloids

HN

O

N H

N H

738 Dragmacidin D Type: Bisindole alkaloids. C25H21BrN7O21+ Yellow solid, [α]D = +12° (c = 0.95, EtOH). Source: Sponge Spongosorites sp. (deep water). Pharm: Cytotoxic (P388, IC50 = 1.4 μg/mL; A549, IC50 = 4.4 μg/mL); antibacterial (Escherichia coli, MIC = 15.6 μg/mL; Bacillus subtilis, MIC = 3.1 μg/mL); antifungal (Candida albicans, MIC = 15.6 μg/mL; Cryptococcus neoformans, MIC = 3.9 μg/mL); antiviral (inhibits replication of feline leukaemia virus). Ref: A. E. Wright, et al, JOC, 1992, 57, 4772

H N O

H N H N

N Br

OH

N

N H

+

NH2

H

739 Echinosulfonic acid A Type: Bisindole alkaloids. C21H18Br2N2O6S Orange oil. Source: Sponge Echinodictyum sp. (depth of 65 m, rawling operation, Great Australian Bight, July 1995, Museum of Victoria Registry Number F79983). Pharm: Antibacterial. Ref: S. P. B. Ovenden, et al, JNP, 1999, 62, 1246 O OH

O S

O 1''

Br

N

N O

Br

H

O

740 Echinosulfonic acid B Type: Bisindole alkaloids. C20H16Br2N2O6S Orange oil. Source: Sponges Echinodictyum sp. (depth of 65 m, rawling operation, Great Australian Bight, July 1995, Museum of Victoria Registry Number F79983) and Psammoclemma sp. Pharm: Antibacterial. Ref: S. P. B. Ovenden, et al, JNP, 1999, 62, 1246│ S. Rubnov, et al, Nat. Prod. Res., 2005, 19, 75; 2006, 20, 517

3.4 Bisindole Alkaloids

261

O OH

O S

O 1''

N

N

Br

Br

H

O O

741 Echinosulfonic acid C Type: Bisindole alkaloids. C19H14Br2N2O6S Orange oil. Source: Sponge Echinodictyum sp. (depth of 65 m, rawling operation, Great Australian Bight, July 1995, Museum of Victoria Registry Number F79983). Pharm: Antibacterial. Ref: S. P. B. Ovenden, et al, JNP, 1999, 62, 1246 O OH

HO S

O 1''

N

N

Br

O

Br

H

O

742 Echinosulfonic acid C 1′′-deoxy Type: Bisindole alkaloids. C19H14Br2N2O5S Brown amorph. solid. Source: Sponge Psammoclemma sp. Pharm: Cytotoxic. Ref: S. Rubnov, et al, Nat. Prod. Res., 2005, 19, 75; 2006, 20, 517 OH O S O 1''

N

N

Br

O

O

Br

H

743 Halichrome A Type: Bisindole alkaloids. C18H16N2O Source: Sponge Halichondria okadai (metagenomic library). Pharm: Cytotoxic (B16). Ref: T. Abe, et al, Chem. Lett., 2012, 41, 728 O

N H

N H

262

3 Pyrrole Indole and Imidazole Alkaloids

744 3-(3-(2-Hydroxyethyl)-(1H-indol-2-yl)-3-(1H-indol-3-yl)propane-1,2-diol) Type: Bisindole alkaloids. C21H22N2O3 Source: Marine actinomycete Rubrobacter radiotolerans. Pharm: AchE inhibitor. Ref: J. L. Li, et al, Fitoterapia, 2015, 102, 203 OH OH N H

OH

N H

745 2-(2-(3-Hydroxy-1-(1H-indol-3-yl)-2-methoxypropyl)-1H-indol-3-yl) acetic acid Type: Bisindole alkaloids. C22H22N2O4 Source: Marine actinomycete Rubrobacter radiotolerans. Pharm: AchE inhibitor. Ref: J. L. Li, et al, Fitoterapia, 2015, 102, 203 OH

O

OH N H

O

N H

746 Hyrtimomine A Type: Bisindole alkaloids. C19H11N3O2 Dark-brown amorphous solid. Source: Sponge Hyrtios sp. (Kerama I., Okinawa). Pharm: Cytotoxic (KB, IC50 = 3.1 μg/mL; L1210, IC50 = 4.2 μg/mL); antimicrobial. Ref: R. Momose, et al, Org. Lett., 2013, 15, 2010│ R. Momose, et al, Org. Lett., 2013, 15, 2010 HO HN NH N

O

747 Hyrtimomine D Type: Bisindole alkaloids. C28H22N5O3S1+ Source: Sponge Hyrtios sp. (Kerama I., Okinawa). Pharm: Antifungal (Candida albicans and Trichophyton mentagrophytes, MIC = 4–16 μg/mL); antibacterial (Cryptococcus neoformans and Staphylococcus aureus, MIC = 4–16 μg/mL). Ref: N. Tanaka, et al, Tet. Lett., 2013, 54, 4038

3.4 Bisindole Alkaloids

263

HO

N

N

S

O HO

N

N

+

N H

748 Hyrtimomine E Type: Bisindole alkaloids. C29H22N5O5S1+ Source: Sponge Hyrtios sp. (Kerama I., Okinawa). Pharm: Antifungal (Candida albicans and Trichophyton mentagrophytes, MIC = 4–16 μg/mL); antibacterial (Cryptococcus neoformans and Staphylococcus aureus, MIC = 4–16 μg/mL). Ref: N. Tanaka, et al, Tet. Lett., 2013, 54, 4038 HO

O OH N

N

S

O HO

N

+

N

N H

749 Hyrtimomine F Type: Bisindole alkaloids. C20H13N3O5 Source: Sponge Hyrtios sp. (Okinawa). Pharm: Antimicrobial. Ref: N. Tanaka, et al, Tetrahedron, 2014, 70, 832 H N O O

OH O

N H

HO N H

750 Hyrtimomine G Type: Bisindole alkaloids. C20H16N2O6 Source: Sponge Hyrtios sp. (Okinawa). Pharm: Antimicrobial. Ref: N. Tanaka, et al, Tetrahedron, 2014, 70, 832

264

3 Pyrrole Indole and Imidazole Alkaloids

OH

HO

O O HN

NH HO

OH

751 Hyrtinadine A Type: Bisindole alkaloids. C20H14N4O2 Source: Sponge Hyrtios sp. SS-1127 (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 1 μg/mL, KB, IC50 = 3 μg/mL). Ref: T. Endo, et al, JNP, 2007, 70, 423 HO

OH

N HN

NH

N

752 Iheyamine A Type: Bisindole alkaloids. C19H13N3O Amorph. purple solid (trifluoroacetate). Source: Ascidian Polycitorella sp. (Okinawa). Pharm: Cytotoxic (P388, A549, HT29, IC50 = 1 μg/mL). Ref: T. Sasaki, et al, Tet. Lett., 1999, 40, 303 N O N

N H

753 Iheyamine B Type: Bisindole alkaloids. C25H23N3O3 Amorph. purple solid, [α]D25 = −16° (c = 0.0002, CHCl3). Source: Ascidian Polycitorella sp. (Okinawa). Pharm: Cytotoxic (P388, A549, HT29, IC50 = 1 μg/mL). Ref: T. Sasaki, et al, Tet. Lett., 1999, 40, 303 O O N O N

N H

754 Lynamicin A Type: Bisindole alkaloids. C22H15Cl2N3O2 Off-white solid, mp 127–130 °C. Source: Marine bacterium Marinospora sp. NPS12745. Antibacterial (MRSA, MIC = 1.8–9.5 μg/mL);

3.4 Bisindole Alkaloids

265

antibacterial (MRSA and VREF); antimicrobial (broad spectrum). Ref: K. A. McArthur, et al, JNP, 2008, 71, 1732 H

O

N O

Cl

Cl

N H

N H

755 Lynamicin B Type: Bisindole alkaloids. C22H14Cl3N3O2 Off-white solid. Source: Marine bacterium Marinospora sp. NPS12745. Pharm: Antibacterial (MRSA, MIC = 1.8–9.5 μg/mL), antibacterial (MRSA and VREF); antimicrobial (broad spectrum). Ref: K. A. McArthur, et al, JNP, 2008, 71, 1732 H

O

N O

Cl

Cl

Cl N H

N H

756 Lynamicin C Type: Bisindole alkaloids. C20H11Cl4N3 Off-white solid. Source: Marine bacterium Marinospora sp. NPS12745. Pharm: Antibacterial (MRSA, MIC = 1.8–9.5 μg/mL), antibacterial (MRSA and VREF); antimicrobial (broad spectrum). Ref: K. A. McArthur, et al, JNP, 2008, 71, 1732 H N Cl

Cl

Cl

Cl N H

N H

757 Lynamicin D Type: Bisindole alkaloids. C24H17Cl2N3O4 Off-white solid, mp 137–140 °C. Source: Marine bacterium Marinospora sp. NPS12745. Pharm: Antibacterial (MRSA, MIC = 1.8–9.5 μg/mL), antibacterial (MRSA and VREF); antimicrobial (broad spectrum); inhibitors of topoisomerase II, cathepsin K, cytochrome P450 3A4, aromatase P450, protein kinase and histone deacetylase (potent). Ref: K. A. McArthur, et al, JNP, 2008, 71, 1732│K. Saurav, et al, Interdiscip. Sci. Comput. Life Sci., 2014, 6, 187

266

3 Pyrrole Indole and Imidazole Alkaloids

H

O

O

N O

Cl

O

Cl

N H

N H

758 Lynamicin E Type: Bisindole alkaloids. C24H18ClN3O4 Off-white solid. Source: Marine bacterium Marinospora sp. NPS12745. Pharm: Antibacterial (MRSA and VREF); antimicrobial (broad spectrum). Ref: K. A. McArthur, et al, JNP, 2008, 71, 1732 H

O

O

N O

O

Cl

N H

N H

759 Metagenediindole A Type: Bisindole alkaloids. C18H16N2O Source: Deep-sea bacterium Escherichia coli (sediment). Pharm: Cytotoxic (CNE2, Bel7402 and HT1080, IC50 = 34.25–50.55 μg/mL). Ref: X. Yan, et al, Mar. Drugs, 2014, 12, 2156 O

N H N H

760 Metagenetriindole A Type: Bisindole alkaloids. C26H19N3O Source: Deep-sea bacterium Escherichia coli (sediment). Pharm: Cytotoxic (CNE2, Bel7402 and HT1080, IC50 = 34.25–50.55 μg/mL). Ref: X. Yan, et al, Mar. Drugs, 2014, 12, 2156 H N O

N H

N H

3.4 Bisindole Alkaloids

267

761 3,3′-Methylenebisindole Arundine Type: Bisindole alkaloids. C17H14N2 Needles (EtOH aq), mp 165–166 °C. Source: Marine bacterium Vibrio parahaemolyticus Bio249 (psychrophilic, cold water, North Sea). Pharm: Cytotoxic (various potent anticancer props). Ref: R. Veluri, et al, JNP, 2003, 66, 1520│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) H

H

N H

N H

762 Nortopsentin A Type: Bisindole alkaloids. C19H12Br2N4 Oil. Source: Sponges Spongosorites ruetzleri and Halichondria sp. Pharm: Cytotoxic (P388, IC50 = 7.6 μg/mL); antifungal (Candida albicans, MIC = 3.1 μg/mL). Ref: S. Sakemi, et al, JOC, 1991, 56, 4304 Br

Br

H N N N H

N H

763 Nortopsentin B Type: Bisindole alkaloids. C19H13BrN4 Plates (EtOAc/CHCl3), mp 250–270 °C (dec). Source: Sponges Spongosorites ruetzleri and Halichondria sp. Pharm: Cytotoxic (P388, IC50 = 7.8 μg/mL); antifungal (Candida albicans, MIC = 6.2 μg/mL). Ref: S. Sakemi, et al, JOC, 1991, 56, 4304 H N

Br

N N H

N H

764 Nortopsentin C Type: Bisindole alkaloids. C19H13BrN4 Oil. Source: Sponges Spongosorites ruetzleri and Halichondria sp. Pharm: Cytotoxic (P388, IC50 = 1.7 μg/mL); antifungal (Candida albicans, MIC = 12.5 μg/mL). Ref: S. Sakemi, et al, JOC, 1991, 56, 4304 Br

H N N N H

N H

268

3 Pyrrole Indole and Imidazole Alkaloids

765 Nortopsentin D Type: Bisindole alkaloids. C23H17Br2N7O Amorph. solid. Source: Sponge Dragmacidon sp. (deep water, Indo-Pacific). Pharm: Cytotoxic. Ref: I. Mancini, et al, Helv. Chim. Acta, 1996, 79, 2075 NH2 N

NH N

H N Br O

Br N H N H

766 Racemosine A Racemosin A Type: Bisindole alkaloids. C20H14N2O4 Source: Green alga Caulerpa racemosa. Pharm: Neuroprotective (against Aβ25–35-induced SH-SY5Y cell damage). Ref: D. -Q. Liu, et al, Fitoterapia, 2013, 91, 15│ H. Yang, et al, J. Asian Nat. Prod. Res., 2014, 16, 1158 O O

H N

N H O

O

767 Racemosine B Racemosin B Type: Bisindole alkaloids. C22H14N2O2 Source: Green alga Caulerpa racemosa. Pharm: Neuroprotective (against Aβ25–35-induced SH-SY5Y cell damage). Ref: D. -Q. Liu, et al, Fitoterapia, 2013, 91, 15│ H. Yang, et al, J. Asian Nat. Prod. Res., 2014, 16, 1158

HN

N H O

O

768 Rhopaladin B Type: Bisindole alkaloids. C21H14N4O3 Amorph. red solid. Source: Ascidian Rhopalaea sp. (Okinawa). Pharm: Orycyclin dependent kinase 4 inhibitor (IC50 = 12.5 μg/mL); c-erbB-2 kinase inhibitor (IC50 = 7.4 μg/mL). Ref: H. Sato, et al, Tetrahedron, 1998, 54, 8687

3.4 Bisindole Alkaloids

269

O NH O

N N H

HO

N H

769 Rhopaladin C Type: Bisindole alkaloids. C21H13BrN4O2 Amorph. red solid. Source: Ascidian Rhopalaea sp. (Okinawa). Pharm: Antibacterial (Sarcina lutea, MIC = 16 μg/mL, Corynebacterium xerosis, MIC = 16 μg/mL). Ref: H. Sato, et al, Tetrahedron, 1998, 54, 8687 O NH O

N

Br N H

N H

770 Rivularin D1 Type: Bisindole alkaloids. C17H11Br3N2O Prisms (CHCl3), mp 220–223 °C, [α]D20 = +8.5° (c = 1, CHCl3). Source: Cyanobacterium Rivularia firma (intertidal). Pharm: Anti-inflammatory. Ref: R. S. Norton, et al, JACS, 1982, 104, 3628 H N Br Br Br N H O

771 Spiroindimicin B Type: Bisindole alkaloids. C23H17Cl2N3O2 Source: Deep-sea-derived streptomycete Streptomyces sp. SCSIO 03032 (sediment, Bay of Bengal). Pharm: Cytotoxic (CCRFCEM, B16, HepG2 and H460, moderate). Ref: W. Zhang, et al, Org. Lett., 2012, 14, 3364

270

3 Pyrrole Indole and Imidazole Alkaloids

H N

O O N

Cl N H Cl

772 Spiroindimicin C Type: Bisindole alkaloids. C22H15Cl2N3O2 Source: Deep-sea-derived streptomycete Streptomyces sp. SCSIO 03032 (sediment, Bay of Bengal). Pharm: Cytotoxic (CCRFCEM, B16, HepG2 and H460, moderate); inhibitors of topoisomerase II, cathepsin K, cytochrome P450 3A4, aromatase P450, protein kinase and histone deacetylase (potent). Ref: W. Zhang, et al, Org. Lett., 2012, 14, 3364│K. Saurav, et al, Interdiscip. Sci. Comput. Life Sci., 2014, 6, 187 H N

O O HN

Cl N H Cl

773 Spiroindimicin D Type: Bisindole alkaloids. C25H19Cl2N3O4 Source: Deep-sea-derived streptomycete Streptomyces sp. SCSIO 03032 (sediment, Bay of Bengal). Pharm: Cytotoxic (CCRFCEM, B16, HepG2 and H460, moderate); inhibitors of topoisomerase II, cathepsin K, cytochrome P450 3A4, aromatase P450, protein kinase and histone deacetylase (potent). Ref: W. Zhang, et al, Org. Lett., 2012, 14, 3364│K. Saurav, et al, Interdiscip. Sci. Comput. Life Sci., 2014, 6, 187 H N

O O

O O

N Cl N H Cl

3.4 Bisindole Alkaloids

271

774 2,2′,5,5′-Tetrabromo-3,3′-bi-1H-indole Rivularin C Type: Bisindole alkaloids. C16H8Br4N2 Rosettes (CHCl3), mp 239–240 °C. Source: Cyanobacterium Rivularia firma. Pharm: Anti-inflammatory. Ref: R. S. Norton, et al, JACS, 1982, 104, 3628 H N Br Br Br Br N H

775 (+)-2,3′,5,5′-Tetrabromo-7′-methoxy-3,4′-bi-1H-indole Rivularin D3 Type: Bisindole alkaloids. C17H10Br4N2O Prisms (CH2Cl2/hexane), mp 178–179 °C (dec), [α]D20 = +71° (c = 1, CHCl3). Source: Cyanobacterium Rivularia firma (intertidal). Pharm: Anti-inflammatory; antiallergic, CNS depressant; tremorgenic. Ref: R. S. Norton, et al, JACS, 1982, 104, 3628 H N Br Br Br Br N H O

776 Topsentin Type: Bisindole alkaloids. C20H14N4O2 Amorph. bright yellow solid, mp 270 °C. Source: Sponges Topsentia genitrix and Spongosorites sp. (deep sea, Caribbean). Pharm: Antiviral (HSV-1, Vesicular stomatitis virus, and corona virus A-59 in vitro); cytotoxic (HCT8, A549 and T47D, IC50 = 20 μg/mL, P388, IC50 = 3.0 μg/mL); toxic (fish and dissociated cell of freshwater sponge Ephydatia fluviatilis). Ref: K. Bartik, et al, Can. J. Chem., 1987, 65, 2118│ S. Tsujii, et al, JOC, 1988, 53, 5446│ I. Kawasaki, et al, Heterocycles, 1998, 48, 1887 O

N NH

N H

N H

OH

777 Topsentin B2 Bromotopsentin Type: Bisindole alkaloids. C20H13BrN4O2 Bright yellow cryst. (CHCl3/MeOH) or yellow–green oil, mp 260 °C, mp 296–297 °C. Source: Sponges

272

3 Pyrrole Indole and Imidazole Alkaloids

Topsentia genitrix, Spongosorites sp. and Hexadella sp. Pharm: Ichthyotoxin; antiviral; antineoplastic; pesticide (weak). Ref: K. Bartik, et al, Can. J. Chem., 1987, 65, 2118│ S. A. Morris, et al, Can. J. Chem., 1989, 67, 677 Br O

21

N HO

6

N H

NH

HN

3.5 Carbazole Alkaloids 778 Antipathine A Type: Carbazole alkaloids. C16H13N3O2 Yellow powder. Source: Black coral Antipathes dichotoma (Sanya, Hainan Province, South China Sea). Pharm: Cytotoxic (SGC7901 and HepG2). Ref: S. -H. Qi, et al, CPB, 2009, 57, 87

N N H

N

O

O

779 7-Bromo-1-(6-bromo-1H-indol-3-yl)-9H-carbazole Type: Carbazole alkaloids. C20H12Br2N2 Source: Sponge Penares sp. (South China Sea). Pharm: Cytotoxic (HL60, IC50 = 16.1μmiol/L, HeLa, IC50 = 33.2 μmol/L). Ref: E. G. Lyakhova, et al, Tet. Lett., 2012, 53, 6119

Br

N H

NH

Br

780 Chloroxiamycin Type: Carbazole alkaloids. C23H24ClNO3 Gray powder, [α]D21 = +69° (c = 0.45, MeOH). Source: Marine-derived streptomycete Streptomyces sp. SCSIO 02999 (sediment, South China Sea). Pharm: Antibacterial (Escherichia coli ATCC 25922, MIC = 64 μg/mL, Staphylococcus aureus ATCC 29213, MIC = 64 μg/mL, Bacillus subtilis SCSIO BS01, MIC > 128 μg/mL, Bacillus thuringiensis SCSIO BT01, MIC = 64 μg/mL). Ref: Q. Zhang, et al, EurJOC, 2012, 27, 5256

3.5 Carbazole Alkaloids

273

OH

H

COOH

N H Cl

781 Coproverdine Type: Carbazole alkaloids. C15H11NO6 Yellow oil, [α]D20 = −8° (c = 0.36, EtOH). Source: An unidentified ascidian (New Zealand). Pharm: Cytotoxic (P388, IC50 = 1.6 μmol/L; A549, IC50 = 0.3 μmol/L; HT29, IC50 = 0.3 μmol/L; MEL28, IC50 = 0.3 μmol/L; DU145, IC50 = 0.3 μmol/L). Ref: S. Urban, et al, JNP, 2002, 65, 1371 O

N OH OH O

O

O

782 Dixiamycin A Type: Carbazole alkaloids. C46H48N2O6 Gray powder, [α]D21 = +90° (c = 0.40, MeOH), first example of naturally occurring N–N-coupled atropo-diastereomers. Source: Marine-derived streptomycete Streptomyces sp. SCSIO 02999 (sediment, South China Sea). Pharm: Antibacterial (Escherichia coli ATCC 25922, MIC = 8 μg/mL, Staphylococcus aureus ATCC 29213, MIC = 8 μg/mL, Bacillus subtilis SCSIO BS01, MIC = 16 μg/mL, Bacillus thuringiensis SCSIO BT01, MIC = 4 μg/mL). Ref: Q. Zhang, et al, EurJOC, 2012, 27, 5256 OH O H (aR)

O

N

OH

N H

HO HO

783 Dixiamycin B Type: Carbazole alkaloids. C46H48N2O6 Gray powder, [α]D21 = +20° (c = 0.32, MeOH). Source: Marine-derived streptomycete Streptomyces sp. SCSIO 02999 (sediment, South China Sea). Pharm: Antibacterial (Escherichia coli ATCC 25922, MIC = 8 μg/mL, Staphylococcus aureus ATCC 29213, MIC = 16 μg/mL, Bacillus subtilis

274

3 Pyrrole Indole and Imidazole Alkaloids

SCSIO BS01, MIC = 16 μg/mL, Bacillus thuringiensis SCSIO BT01, MIC = 8 μg/mL). Ref: Q. Zhang, et al, EurJOC, 2012, 27, 5256 HO HOOC H N

(aS)

N H COOH OH

784 1-Methyl-9H-carbazole Type: Carbazole alkaloids. C13H11N Plates (petrol), mp 120.5 °C. Source: Sponge Tedania ignis. Pharm: Toxic (brine shrimp); insecticide. Ref: R. L. Dillman, et al, JNP, 1991, 54, 1056

9

N H

785 Oxiamycin Type: Carbazole alkaloids. C23H25NO4 Gray powder, [α]D21 = +83° (c = 0.48, MeOH). Source: Marine-derived streptomycete Streptomyces sp. SCSIO 02999 (sediment, South China Sea). Pharm: Antibacterial (Escherichia coli ATCC 25922, MIC = 64 μg/mL, Staphylococcus aureus ATCC 29213, MIC = 128 μg/mL, Bacillus subtilis SCSIO BS01, MIC > 128 μg/mL, Bacillus thuringiensis SCSIO BT01, MIC > 128 μg/mL). Ref: Q. Zhang, et al, EurJOC, 2012, 27, 5256 OH O H COOH N H

786 Xiamycin Xiamycin A Type: Carbazole alkaloids. C23H25NO3 Pale-yellow powder, [α]D21 = +137° (c = 6.7, MeOH). Source: Mangrove-derived streptomycete Streptomyces sp. GT2002/ 1503 (endophytic) from mangrove Bruguiera gymnorrhiza (stem), marine-derived streptomycete Streptomyces sp. (sediment, South China Sea). Pharm: Antibacterial (Escherichia coli ATCC 25922, MIC = 64 μg/mL, Staphylococcus aureus ATCC 29213, MIC = 64 μg/mL, Bacillus subtilis SCSIO BS01, MIC > 128 μg/mL, Bacillus

3.6 Indolo[2,3-α]carbazole Alkaloids

275

thuringiensis SCSIO BT01, MIC > 128 μg/mL); cytotoxic (panel of assays, weak to moderate); antiviral (selective anti-HIV agent by blocking R5-tropic viruses, without having effects on X4-tropic HIV-1 infections). Ref: Q. Zhang, et al, EurJOC, 2012, 27, 5256│L. Ding, et al, BoMCL, 2010, 20, 6685 OH OH H N H

O

787 Xiamycin A methyl ester Type: Carbazole alkaloids. C24H27NO3 Source: Mangrove-derived streptomycete Streptomyces sp. GT2002/1503 (endophytic) from mangrove Bruguiera gymnorrhiza (stem). Pharm: Cytotoxic (panel of assays, IC50 = 10.13 μmol/L). Ref: L. Ding, et al, BoMCL, 2010, 20, 6685 OH O H N H

O

788 Xiamycin B Type: Carbazole alkaloids. C23H25NO4 Source: Mangrove-derived streptomycete Streptomyces sp. HKI0595 (endophytic) from mangrove Kandelia candel (stem). Pharm: Antibacterial (MRSA and VREF, strong). Ref: L. Ding, et al, Org. Biomol. Chem., 2011, 9, 4029 OH O N H

OH OH

3.6 Indolo[2,3-α]carbazole Alkaloids 789 Antibiotic ZHD-0501 Type: Indolo[2,3-α]carbazole alkaloids. C28H22N4O4 Pale yellow cryst. (CHCl3/ MeOH), mp 283.4–285.5 °C, [α]D20 = +83.2° (c = 0.1, MeOH). Source: Marine-derived actinomycete Actinomadura sp. 007. Pharm: Cytotoxic (1 μmol/L: A549, InRt = 82.6%, Bel7402, InRt = 57.3%, HL60, InRt = 76.1%, P388, InRt = 62.2%); cytotoxic (mouse cancer tsFT210 cell, 2.1 μmol/L, InRt = 20.5%, 21 μmol/L, InRt = 28.3%). Ref: X. -X. Han, et al, Tet. Lett., 2005, 46, 6137

276

3 Pyrrole Indole and Imidazole Alkaloids

H N

O

N

N O

H

O N O

790 Arcyriaflavin A Type: Indolo[2,3-α]carbazole alkaloids. C20H11N3O2 Orange solid, mp 360 °C. Source: Ascidian Eudistoma sp. (West Africa). Pharm: Cytotoxic (strong); PKC inhibitor. Ref: P. A. Horton, et al, Experientia, 1994, 50, 843 H N

O

N H

O

N H

791 N-Carboxamido-staurosporine Type: Indolo[2,3-α]carbazole alkaloids. C29H27N5O4 Light yellow solid. Source: Marinederived streptomycete Streptomyces sp. QD518. Pharm: Cytotoxic (panel of 37 cell lines, mean IC50 = 0.016 μg/mL, mean IC70 = 0.171 μg/mL, mean IC90 = 2.35 μg/mL, total selectivity = 10/37, Selectivity = 27%); antibacterial (Streptomyces viridochromogenes; 40 μg/paper disk, ID = 11 mm); anti-microalgal (Chlorella vulgaris, Chlorella sorokiniana and Scenedesmus subspicatus, 40 μg/paper disk, ID = 14–16 mm). Ref: S. J. Wu, et al, J. Antibiot. 2006, 59, 331 H N

O

N

N H

O O

H2N

N O

3.6 Indolo[2,3-α]carbazole Alkaloids

277

792 Fradcarbazole A Type: Indolo[2,3-α]carbazole alkaloids. C39H32N6O3S Yellow amorph. powder, [α]D21 = +31° (c = 0.3, CHCl3). Source: Marine-derived streptomycete Streptomyces fradiae 007M135 (sediment, Jiaozhou Bay, Shandong, China). Pharm: Cytotoxic (HL60, IC50 = 1.30 μmol/L, control Adriamycin, IC50 = 0.65 μmol/L; K562, IC50 = 4.58 μmol/L, Adriamycin, IC50 = 0.64 μmol/L; A549, IC50 = 1.41 μmol/L, Adriamycin, IC50 = 0.08 μmol/L; Bel7402, IC50 = 3.26 μmol/L, Adriamycin, IC50 = 0.37 μmol/L); PKC-α inhibitor (IC50 = 4.27 μmol/L, control Staurosporine, IC50 = 0.16 μmol/L). Ref: P. Fu, et al, Org. Lett., 2012, 14, 6194 H N

N

O

O

N

O S

N

NH

N

793 Fradcarbazole B Type: Indolo[2,3-α]carbazole alkaloids. C29H27N5O3S Yellow amorph. powder, [α]D21 = +21° (c = 0.2, CHCl3). Source: Marine-derived streptomycete Streptomyces fradiae 007M135 (sediment, Jiaozhou Bay, Shandong, China). Pharm: Cytotoxic (HL60, IC50 = 1.60 μmol/L, control Adriamycin, IC50 = 0.65 μmol/L; K562, IC50 = 1.47 μmol/L, Adriamycin, IC50 = 0.64 μmol/L; A549, IC50 = 0.001 μmol/L, Adriamycin, IC50 = 0.08 μmol/L; Bel7402,IC50 = 1.74 μmol/L, Adriamycin, IC50 = 0.37 μmol/L); PKC-α inhibitor (IC50 = 0.85 μmol/L, control Staurosporine, IC50 = 0.16 μmol/L). Ref: P. Fu, et al, Org. Lett., 2012, 14, 6194 H N

N

O

O

N

O N

NH2 S

278

3 Pyrrole Indole and Imidazole Alkaloids

794 Fradcarbazole C Type: Indolo[2,3-α]carbazole alkaloids. C29H25N5O3 Yellow amorph. powder, [α]D21 = +28° (c = 0.2, CHCl3). Source: Marine-derived streptomycete Streptomyces fradiae 007M135 (sediment, Jiaozhou Bay, Shandong, China). Pharm: Cytotoxic (HL60, IC50 = 0.13 μmol/L, control Adriamycin, IC50 = 0.65 μmol/L; K562, IC50 = 0.43 μmol/L, Adriamycin, IC50 = 0.64 μmol/L; A549, IC50 = 0.02 μmol/L, Adriamycin, IC50 = 0.08 μmol/L; Bel7402, IC50 = 0.68 μmol/L, Adriamycin, IC50 = 0.37 μmol/L); PKC-α inhibitor (IC50 = 1.03 μmol/L, control Staurosporine, IC50 = 0.16 μmol/L). Ref: P. Fu, et al, Org. Lett., 2012, 14, 6194 H N

N

O

O

N

O N

CN

795 11-Hydroxystaurosporine Type: Indolo[2,3-α]carbazole alkaloids. C28H26N4O4 Pale yellow amorph. solid, [α]D = +10.3° (c = 0.3, MeOH). Source: Ascidian Eudistoma sp. (Pohnpei). Pharm: Cytotoxic (KB, IC50 = 0.7 ng/mL; LoVo, IC50 = 0.03 μg/mL); PKC inhibitor (IC50 = 2.2 ng/mL). Ref: R. B. Kinnel, et al, JOC, 1992, 57, 6327 H N

N

O

O

N

OH O NH

796 5′-Hydroxystaurosporine Type: Indolo[2,3-α]carbazole alkaloids. C28H26N4O4 Pale yellow powder, mp > 220 °C (dec), [α]D25 = +53° (c = 0.1, MeOH). Source: Marine bacterium Micromonospora sp. (strain L-31-CLCO-02) from calcareous sponge Clathrina coriacea (homogenate, Canary Is., Spain). Pharm: Cytotoxic. Ref: L. M. Cañedo Hernández, et al, J. Antibiot., 2000, 53, 895

3.6 Indolo[2,3-α]carbazole Alkaloids

H N

N

O

279

O

N

O

OH NH

797 Indimicin B Type: Indolo[2,3-α]carbazole alkaloids. C24H21Cl2N3 Source: Marine-derived streptomycete Streptomyces sp. SCSIO 03032 (deep sea). Pharm: Cytotoxic (MCF7). Ref: W. Zhang, et al, JNP, 2014, 77, 1887 N Cl

Cl

N

H

N H

798 4′-N-Methyl-5′-hydroxystaurosporine Type: Indolo[2,3-α]carbazole alkaloids. C29H28N4O4 Pale yellow powder, mp > 220 °C (dec), [α]D25 = +30° (c = 0.11, CHCl3). Source: Marine bacterium Micromonospora sp. (strain L-31-CLCO-02) from calcareous sponge Clathrina coriacea (homogenate, Canary Is., Spain). Pharm: Cytotoxic. Ref: L. M. Cañedo Hernández, et al, J. Antibiot., 2000, 53, 895 H N

N

O

O

O

N

OH N

799 7-Oxo-8,9-dihydroxy-4′-N-demethylstaurosporine Type: Indolo[2,3-α]carbazole alkaloids. C27H22N4O6 Source: Ascidian Cystodytes solitus. Pharm: Cytotoxic (A549, HT29 and MDA-MB-231, GI50 = 17.5–90 nmol/L). Ref: F. Reyes, et al, JNP, 2008, 71, 1046

280

3 Pyrrole Indole and Imidazole Alkaloids

H N

O

O OH OH

N

O

N

O NH2

800 7-Oxo-2-hydroxystaurosporine 2-Hydroxy-7-oxostaurosporine Type: Indolo[2,3-α]carbazole alkaloids. C28H24N4O5 Source: Ascidian Eudistoma vannamei (underside of beach rocks in intertidal zone of Taíba Beach 03°34,931′S; 038°54,469′W, west coast of Ceara state, Brazil). Pharm: Cytotoxic (mixture of 7-Oxo-2/3-hydroxystaurosporine: HL60, IC50 = 25.97 nmol/L, SI (PBMC vs cabcer cells) = 26.46; Molt4, IC50 = 18.64 nmol/L, SI = 36.86; Jurkat, IC50 = 10.33 nmol/L, SI = 70.08; K562, IC50 144.47 = nmol/L, SI = 4.75; HCT8, IC50 = 58.24 nmol/L, SI = 11.80; SF295, IC50 = 57.90 nmol/L, SI = 11.87; MDA-MB-435, IC50 = 28.68 nmol/L, SI = 23.96; PBMC, IC50 = 687.08 nmol/L). Ref: P. C. Jimenez, et al, Mar. Drugs, 2012, 10, 1092 H N

O

HO

N

O

O

N

O NH

801 7-Oxo-3-hydroxystaurosporine 3-Hydroxy-7-oxostaurosporine Type: Indolo[2,3-α]carbazole alkaloids. C28H24N4O5 Source: Ascidian Eudistoma vannamei (underside of beach rocks in intertidal zone of Taíba Beach 03°34,931′S; 038°54,469′W, west coast of Ceara state, Brazil). Pharm: Cytotoxic (mixture of 7-Oxo-2/3-hydroxystaurosporine: HL60, IC50 = 25.97 nmol/L, SI (PBMC vs cabcer cells) = 26.46; Molt4, IC50 = 18.64 nmol/L, SI = 36.86; Jurkat, IC50 = 10.33 nmol/L, SI = 70.08; K562, IC50 144.47 = nmol/L, SI = 4.75; HCT8, IC50 = 58.24 nmol/L, SI = 11.80; SF295, IC50 = 57.90 nmol/L, SI = 11.87; MDA-MB-435, IC50 = 28.68 nmol/L, SI = 23.96; PBMC, IC50 = 687.08 nmol/L). Ref: P. C. Jimenez, et al, Mar. Drugs, 2012, 10, 1092

3.6 Indolo[2,3-α]carbazole Alkaloids

H N

O

281

O

HO

N

O

N

O NH

802 7-Oxo-3,8,9-trihydroxystaurosporine Type: Indolo[2,3-α]carbazole alkaloids. C28H24N4O7 Source: Ascidian Cystodytes solitus. Pharm: Cytotoxic (A549, HT29 and MDA-MB-231, GI50 = 17.5–90 nmol/L). Ref: F. Reyes, et al, JNP, 2008, 71, 1046 H N

O

O OH OH

HO

N

O

N

O NH

803 Staurosporine Type: Indolo[2,3-α]carbazole alkaloids. C28H26N4O3 Pale yellow plates, mp 270 °C (dec), [α]D25 = +35° (c = 1, MeOH). Source: Ascidian Eudistoma vannamei (underside of beach rocks in intertidal zone of Taíba Beach 03°34,931′S; 038°54,469′W, west coast of Ceara state, Brazil), an unidentified marine-derived actinomycete N96C-47 from ascidian Eudistoma toealensis, flatworm Pseudoceros sp. (predator of ascidian Eudistoma toealensis). Pharm: Cytotoxic (mixture of 7-Oxo-2/3-hydroxystaurosporine: HL60, IC50 = 391.83 nmol/L, SI (PBMC vs cabcer cells) = 2.00; Molt4, IC50 = 154.50 nmol/L, SI = 5.08; Jurkat, IC50 = 83.96 nmol/L, SI = 9.34; HCT8, IC50 = 83.83 nmol/L, SI = 9.36; SF295, IC50 = 569.52 nmol/L, SI = 1.38; MDAMB-435, IC50 = 215.42 nmol/L, SI = 3.64; PBMC, IC50 = 784.51 nmol/L); antifungi; hypotensive; platelet aggregation inhibitor; antiparasitic; nematocide; vasorelaxant; smooth muscle relaxant; neurotropic; antihyperplastic; endothelin agonist; cell cycle progression inhibitor. Ref: D. E. Williams, et al, Tet. Lett., 1999, 40, 7171│ P. C. Jimenez, et al, Mar. Drugs, 2012, 10, 1092│ CRC Press, DNP on DVD, 2012, version 20.2

282

3 Pyrrole Indole and Imidazole Alkaloids

H N

O

5 7 8 3 2

N

N

O

11

4'

5'

O NH

804 Staurosporine aglycone Type: Indolo[2,3-α]carbazole alkaloids. C20H13N3O Pale yellow needles, mp > 300 °C. Source: Ascidian Eudistoma sp. (West Africa). Pharm: Cytotoxic (A549, IC50 = 2.0 μmol/L, P388, IC50 = 3.2 μmol/L); PKCs inhibitor (seven of eigut cloned PKC isoenzymes: α-PKC, IC50 = 1.3 μmol/L, βI-PKC, IC50 = 0.6 μmol/L, βII-PKC, IC50 = 0.5 μmol/ L, δ-PKC, IC50 = 1.2 μmol/L, ε-PKC, IC50 = 1.1 μmol/L, η-PKC, IC50 = 0.8 μmol/L, γPKC, IC50 = 1.5 μmol/L, ζ-PKC, IC50 > 6.4 μmol/L); PKC inhibitor (IC50 = 0.2 μmol/L) (Yasuza, 1986); cell adhesion inhibitor (EL-4 cell line, IC50 = 30 μmol/L, inhibiting ‘blebbing” in K562 bleb assay, IC50 = 0.9 μmol/L) (Osada, 1988); oxygen release inhibitor (neutrophil burst assay, IC50 = 0.5 μmol/L). Ref: P. A. Horton, et al, Experientia, 1994, 50, 843│ T. Yasuza, et al, J. Antibiot., 1986, 39, 1072│ H. Osada, et al, J. Antibiot., 1988, 41, 925 H N

O

N H

N H

805 Streptocarbazole A Type: Indolo[2,3-α]carbazole alkaloids. C28H23N3O5 Source: Mangrove-derived streptomycete Streptomyces sp. from an unidentified mangrove (soil, Sanya, Hainan, China). Pharm: Cytotoxic (HL60, IC50 = 1.4 μmol/L; A549, IC50 = 5.0 μmol/L; P388, IC50 = 18.9 μmol/L; HeLa, IC50 = 34.5 μmol/L); cytotoxic (HeLa, 10 μmol/L, arrested cell cycle G2/ M phase). Ref: P. Fu, et al, Org. Lett., 2012, 14, 2422

3.7 β-Carboline Alkaloids

H N

N

283

O

N

O

O

O

OH

806 Tjipanazole A1 N-(6-Deoxy-β-D-gulopyranosyl)-tjipanazole D Type: Indolo[2,3-α]carbazole alkaloids. C24H20Cl2N2O4 [α]D = +9.1° (c = 1.0, CHCl3). Source: Cyanobacterium Tolypothrix tjipanasensis. Pharm: Antifungal. Ref: R. Bonjouklian, et al, Tetrahedron, 1991, 47, 7739 Cl N HO

O

HN Cl

OHOH

807 Tjipanazole A2 N-α-L-Rhamnopyranosyl-tjipanazole D Type: Indolo[2,3-α]carbazole alkaloids. C24H20Cl2N2O4 [α]D = +25.12° (c = 1.0, CHCl3). Source: Cyanobacterium Tolypothrix tjipanasensis. Pharm: Antifungal. Ref: R. Bonjouklian, et al, Tetrahedron, 1991, 47, 7739 Cl N OH O

HN Cl

OHOH

3.7 β-Carboline Alkaloids 808 Arborescidine D Type: β-Carboline alkaloids. C16H19BrN2O Amorph. solid. Source: Ascidian Pseudodistoma arborescens. Pharm: Cytotoxic (KB). Ref: M. Chbani, et al, JNP, 1993, 56, 99

284

3 Pyrrole Indole and Imidazole Alkaloids

N H N

Br HO

17 16

809 Brocaeloid C Type: β-Carboline alkaloids. C17H22N2O Source: Mangrove-derived fungus Penicillium brocae MA-192 from mangrove Avicennia marina (fresh leaves). Pharm: Antibacterial (weak or inactive). Ref: P. Zhang, et al, EurJOC, 2014, 2014, 4029 O H N

N H

810 3-Bromofascaplysin Type: β-Carboline alkaloids. C18H10BrN2O1+ Red solid (chloride). Source: Sponge Fascaplysinopsis reticulata, ascidian Didemnum sp. Pharm: Cytotoxic (HL60, THP-1, HeLa, MDA-MB-231, DLD-1, SNU-C4 and SK-MEL-28, mediated by caspase-8, caspase-9, caspase-3-dependent apoptosis). Ref: N. L. Segraves, et al, Tet. Lett., 2003, 44, 3471│ A. S. Kuzmich, et al, Bioorg. Med. Chem., 2010, 18, 3834 O

3

H N 10

N

+

Br

811 3-Bromohomofascaplysin A Type: β-Carboline alkaloids. C20H14BrN2O31+ Amorph. pale yellow–brown solid, [α]D20 = −9° (c = 0.1, MeOH). Source: Ascidian Didemnum sp. (Pratt Reef, Fiji). Pharm: Antiplasmodial life stage-specific activity (Plasmodium falciparum strain W2-Mef, All live parasites, IC50 = 805 nmol/L, control Chloroquite, IC50 = 149 nmol/L, control Artermisinin, IC50 = 6.245 nmol/L; Rings stage, IC50 = 574 nmol/L, Chloroquite, IC50 = 174 nmol/L, Artermisinin, IC50 = 5.92 nmol/L; Trophozoites stage, IC50 = 1189 nmol/L, Chloroquite, IC50 = 162 nmol/L, Artermisinin, IC50 = 6.46 nmol/L; Schizonts stage, IC50 = 765 nmol/L, Chloroquite, IC50 = 80 nmol/L, Artermisinin, IC50 = 5.91 nmol/L). Ref: Z. Lu, et al, BoMC, 2011, 19, 6604

3.7 β-Carboline Alkaloids

N

+

285

Br

N H HO OH O

812 1-Deoxysecofascaplysin A Type: β-Carboline alkaloids. C19H15N2O21+ Light yellow solid. Source: Sponge Thorectandra sp. Pharm: Cytotoxic. Ref: R. D. Charan, et al, Nat. Prod. Res., 2004, 18, 225

N N H

+

O O

813 Didemnoline A Type: β-Carboline alkaloids. C16H13BrN4S Source: Ascidian Didemnum sp. (Rota, Northern Mariana Is., Pacific Ocean). Pharm: Cytotoxic (KB). Ref: R. W. Schumacher, et al, Tetrahedron, 1995, 51, 10125│ R. W. Schumacher, et al, Tetrahedron, 1999, 55, 935

Br

N

N N N H

S

814 Didemnoline B Type: β-Carboline alkaloids. C16H14N4S Source: Ascidian Didemnum sp. (Rota, Northern Mariana Is., Pacific Ocean). Pharm: Cytotoxic (KB). Ref: R. W. Schumacher, et al, Tetrahedron, 1995, 51, 10125│ R. W. Schumacher, et al, Tetrahedron, 1999, 55, 935

N

N N S

N H

286

3 Pyrrole Indole and Imidazole Alkaloids

815 Didemnoline C Type: β-Carboline alkaloids. C16H13BrN4OS [α]D25 = +97.2° (c = 0.1, DMSO). Source: Ascidian Didemnum sp. (Rota, Northern Mariana Is., Pacific Ocean). Pharm: Cytotoxic (KB). Ref: R. W. Schumacher, et al, Tetrahedron, 1995, 51, 10125│ R. W. Schumacher, et al, Tetrahedron, 1999, 55, 935

Br

N

N N N H

S O

816 Didemnoline D Type: β-Carboline alkaloids. C16H14N4OS Source: Ascidian Didemnum sp. (Rota, Northern Mariana Is., Pacific Ocean). Pharm: Cytotoxic (KB). Ref: R. W. Schumacher, et al, Tetrahedron, 1995, 51, 10125│ R. W. Schumacher, et al, Tetrahedron, 1999, 55, 935

N N N N H

S O

817 Dysideanin B Type: β-Carboline alkaloids. C14H16N3O1+ Source: Sponge Dysidea sp. (Lingshui County, Hainan, China). Pharm: Antibacterial (weak). Ref: S. Ren, et al, J. Antibiot., 2010, 63, 699 O

N H

N

+

N H

818 1-Ethyl-β-carboline Type: β-Carboline alkaloids. C13H12N2 Whitish-yellow needles (MeOH/CHCl3), mp 194–195 °C. Source: Bryozoans Cribricellina cribraria (New Zealand) and Costaticella hastata. Pharm: Cytotoxic (P388, IC50 = 25000 ng/mL); antibacterial (Escherichia coli, MIC > 120 μg/disc; Bacillus subtilis, MIC = 7.5–15 μg/disc; Pseudomonas

3.7 β-Carboline Alkaloids

287

aeruginosa, MIC > 60 μg/disc); antifungal (Candida albirnns, MIC = 1.9–3.8 μg/disc; Trichophyton mentagropbytes, MIC = 1.9–3.8 μg/disc; Cladzspwum resina, MIC = 30– 60 μg/disc). Ref: A. J. Blackman, et al, JNP, 1987, 50, 494│ M. R. Prinsep, et al, JNP, 1991, 54, 1068

N

N H

819 1-Ethyl-β-carboline-3-carboxylic acid Type: β-Carboline alkaloids. C14H12N2O2 Source: Marine-derived actinomycete Actinomadura sp. BCC 24717. Pharm: Cytotoxic (Vero cells). Ref: J. Kornsakulkarn, et al, Phytochem. Lett., 2013, 6, 491 O OH N N H

820 Eudistalbin A Type: β-Carboline alkaloids. C16H18BrN3 Amorph., [α]D = −10° (c = 0.1, MeOH). Source: Ascidian Eudistoma album (New Caledonia). Pharm: Cytotoxic (KB). Ref: S. A. Adesanya, et al, JNP, 1992, 55, 525

Br

N H

N

H2 N

821 Eudistomidin A Type: β-Carboline alkaloids. C15H12BrN3O Yellow solid, mp 225–230 °C (dec), mp 265–280 °C (dec), mp 260–270 °C (dec). Source: Ascidian Eudistoma glaucus (Okinawa). Pharm: Calmodulin antagonist (powerful). Ref: J. Kobayashi, et al, Tet. Lett., 1986, 27, 1191│ J. Kobayashi, et al, JOC, 1990, 55, 3666│ Y. Murakami, et al, Tetrahedron, 1998, 54, 45 Br

OH

N H

N

N

288

3 Pyrrole Indole and Imidazole Alkaloids

822 Eudistomidin B Type: β-Carboline alkaloids. C21H24BrN3 Yellow foam, mp 81–83 °C, [α]D22 = −54° (c = 0.2, MeOH), [α]D = −76.4° (c = 0.3, CHCl3). Source: Ascidians Eudistoma glaucus and Eudistoma glaucus (Okinawa). Pharm: Cytotoxic (antileukemic: L1210, IC50 = 3.4 μg/mL; L5178Y, IC50 = 3.1 μg/mL); cytotoxic (L1210, = IC50 = 4.7 μg/mL) (Takahashi, 2010); activaterof ATPase (rabbit heart muscle actomyosin, 3 × 10−5 mol/L, 93%). Ref: J. Kobayashi, et al, JOC, 1990, 55, 3666│ Y. Takahashi, et al, BoMCL, 2010, 20, 4100 Br N

N H

H

HN

823 Eudistomidin C Type: β-Carboline alkaloids. C15H16BrN3OS Yellow solid, mp 120–122 °C, [α]D22 = +15.6° (c = 0.2, MeOH). Source: Ascidian Eudistoma glaucus (Okinawa). Pharm: Cytotoxic (antileukemic: L1210, IC50 = 0.36 μg/mL; L5178Y, IC50 = 0.42 μg/mL); calmodulin antagonist (IC50 = 3 × 10−5 mol/L). Ref: J. Kobayashi, et al, JOC, 1990, 55, 3666 Br HO

N H

N 14

S

N H

824 Eudistomidin D Type: β-Carboline alkaloids. C12H9BrN2O Yellow solid, mp 180 °C (dec). Source: Ascidian Eudistoma glaucus (Okinawa). Pharm: Cytotoxic (antileukemic: L1210, IC50 = 2.4 μg/mL; L5178Y, IC50 = 1.8 μg/mL); induces Ca2+ release from sarcoplasmic reticulum (10 times more potent than caffeine). Ref: J. Kobayashi, et al, JOC, 1990, 55, 3666 Br HO

N

N

3.7 β-Carboline Alkaloids

289

825 Eudistomidin G Type: β-Carboline alkaloids. C21H24BrN3 Source: Ascidian Eudistoma glaucus (Ie I., Okinawa). Pharm: Cytotoxic (L1210, IC50 = 4.8 μg/mL). Ref: Y. Takahashi, et al, BoMCL, 2010, 20, 4100

Br

N

N H

H

HN

826 Eudistomidin J Type: β-Carboline alkaloids. C15H16BrN3O2S Pale yellow amorph. solid, [α]D25 = +21.1° (c = 0.5, MeOH). Source: Ascidian Eudistoma glaucus (Ie I., Okinawa). Pharm: Cytotoxic (P388, IC50 = 0.043 μg/mL, L1210, IC50 = 0.047 μg/mL, KB, IC50 = 0.063 μg/ mL). Ref: T. Suzuki, et al, BoMCL, 2011, 21, 4220 HO

Br

N

N H

S

HN

O

827 Eudistomin A Type: β-Carboline alkaloids. C15H10BrN3O Yellow oil. Source: Ascidian Eudistoma olivaceum (Caribbean Sea). Pharm: Antiviral (HSV-1 assay: 500 ng/12.7 mm disk, – (no inhibition)). Ref: J. Kobayashi, et al, JACS, 1984, 106, 1526│ K. L. Rinehart, et al, JACS, 1987, 109, 3378│ P. Molina., Tet. Lett., 1992, 33, 2891 4

5

HO

4a

4b

3

9

Br

8

8a

N H

N 9a

2

1 2'

1'

NH

3' 4'

5'

828 Eudistomin B Type: β-Carboline alkaloids. C17H16BrN3O2 Source: Ascidian Eudistoma olivaceum (Caribbean Sea). Pharm: Antiviral (HSV-1 assay: 500 ng/12.7 mm disk, –

290

3 Pyrrole Indole and Imidazole Alkaloids

(no inhibition));antibacterial (gram-positive bacteria), antifungal (yeasts). Ref: K. L. Rinehart, et al, JACS, 1987, 109, 3378 O Br

N

N H

NH

O

829 Eudistomin C Type: β-Carboline alkaloids. C14H16BrN3O2S Pale-yellow oil, [α]D25 = −52° (c = 0.4, MeOH). Source: Ascidians Eudistoma gilboverde (Palau, Oceania), Eudistoma olivaceum (Caribbean Sea) and Ritterella sigillinoides (New Zealand). Pharm: Antiviral (HSV-1 assay: 50 ng/12.7 mm disk, +++ (complete inhibition); 25 ng/12.7 mm disk, ++ (part inhibition); 10 ng/12.7 mm disk, + (part inhibition); 5 ng/12.7 mm disk, – (no inhibition)); antibacterial (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Bacillus subtilis, IZD = 26 mm; Escherichia coli, IZD = 22 mm; 5 μg/12.7 mm disk, 37 °C, 20h or 16h, Bacillus subtilis, IZD = 14 mm; Escherichia coli, IZD = 0 mm); antifungal (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Saccharomyces cerevisiae, IZD = 0 mm; Penicillium atrovenetum, IZD = 27 mm; 5 μg/12.7 mm disk, 37 °C, 20h or 16h, Saccharomyces cerevisiae, IZD = 0 mm; Penicillium atrovenetum, IZD = 0 mm). Ref: K. L. Rinehart, Jr., et al, JACS, 1984, 106, 1524│ K. L. Rinehart, et al, JACS, 1987, 109, 3378│ J. W. Blunt, et al, Tet. Lett., 1987, 28, 1825│ J. -J. Liu, et al, JCS Perken I, 2000, 3487│ M. A. Rashid, et al, JNP, 2001, 64, 1454 HO

Br

N H

N H

H2N

O

1

S

830 Eudistomin D Type: β-Carboline alkaloids. C11H7BrN2O Yellow amorph. solid, mp > 280 °C. Source: Ascidians Eudistoma olivaceum (Caribbean Sea) and Eudistoma gilboverde (Palau, Oceania). Pharm: Antiviral (HSV-1 assay: 500 ng/12.7 mm disk, + (part inhibition)); antibacterial (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Bacillus subtilis, IZD = 14 mm; Escherichia coli, IZD = 0 mm). Ref: J. Kobayashi, et al, JACS, 1984, 106, 1526│ K. L. Rinehart, et al, JACS, 1987, 109, 3378│ M. A. Rashid, et al, JNP, 2001, 64, 1454

3.7 β-Carboline Alkaloids

291

Br HO N

N H

831 Eudistomin E Type: β-Carboline alkaloids. C14H16BrN3O2S Pale-yellow oil, [α]D25 = −18° (c = 0.1, MeOH). Source: Ascidians Eudistoma gilboverde (Palau, Oceania) and Eudistoma olivaceum (Caribbean Sea). Pharm: Antiviral (HSV-1 assay: 50 ng/12.7 mm disk, +++ (complete inhibition); 25 ng/12.7 mm disk, +++; 5 ng/12.7 mm disk, ± (marginal inhibition)); antibacterial (1 μg/12.7 mm disk, 37 °C, 20h or 16h, Bacillus subtilis, IZD = 17 mm; Escherichia coli, IZD = 0 mm); antifungal (1 μg/12.7 mm disk, 37 °C, 20h or 16h, Saccharomyces cerevisiae, IZD = 0 mm; Penicillium atrovenetum, IZD = 0 mm). Ref: K. L. Rinehart, Jr., et al, JACS, 1984, 106, 1524│ K. L. Rinehart, et al, JACS, 1987, 109, 3378│ J. W. Blunt, et al, Tet. Lett., 1987, 28, 1825│ J. -J. Liu, et al, JCS Perken I, 2000, 3487│ M. A. Rashid, et al, JNP, 2001, 64, 1454 Br HO 9

N

N H H

O S

H 2N

832 Eudistomin F Type: β-Carboline alkaloids. C16H18BrN3O4S Oil. Source: Ascidian Eudistoma olivaceum (Caribbean Sea). Pharm: Antiviral (potent). Ref: K. L. Rinehart, Jr., et al, JACS, 1984, 106, 1524│ K. L. Rinehart, et al, JACS, 1987, 109, 3378│ J. -J. Liu, et al, JCS Perken I, 2000, 3487 HO H Br

N

N H N H

O

O S

O

833 Eudistomin G Type: β-Carboline alkaloids. C15H12BrN3 Needles (CH2Cl2), mp 204–206 °C. Source: Ascidian Eudistoma olivaceum (Caribbean Sea). Pharm: Antiviral (HSV-1 assay: 500 ng/12.7 mm disk, ± (marginal inhibition)). Ref: J. Kobayashi, et al, JACS, 1984, 106, 1526│ K. L. Rinehart, et al, JACS, 1987, 109, 3378

292

3 Pyrrole Indole and Imidazole Alkaloids

Br

N H

N N

834 Eudistomin H Type: β-Carboline alkaloids. C15H12BrN3 Powder, mp 140–142 °C. Source: Ascidian Eudistoma olivaceum (Caribbean Sea). Pharm: Antiviral (HSV-1 assay: 500 ng/12.7 mm disk, + (part inhibition)); antifungal (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Saccharomyces cerevisiae, IZD = 20 mm (faint); Penicillium atrovenetum, IZD = 0 mm). Ref: J. Kobayashi, et al, JACS, 1984, 106, 1526│ K. L. Rinehart, et al, JACS, 1987, 109, 3378 Br N

N H

N

835 Eudistomin I Type: β-Carboline alkaloids. C15H13N3 Powder, mp 153–155 °C. Source: Ascidian Eudistoma olivaceum (Caribbean Sea). Pharm: Antiviral (HSV-1 assay: 500 ng/12.7 mm disk, ± (marginal inhibition)); antibacterial (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Bacillus subtilis, IZD = 14 mm; Escherichia coli, IZD = 0 mm). Ref: J. Kobayashi, et al, JACS, 1984, 106, 1526│ K. L. Rinehart, et al, JACS, 1987, 109, 3378

N

N H

N

836 Eudistomin J Type: β-Carboline alkaloids. C11H7BrN2O Source: Ascidians Eudistoma olivaceum (Caribbean Sea) and Eudistoma gilboverde (Palau, Oceania). Pharm: Antiviral (HSV1 assay: 1000 ng/12.7 mm disk, ± (marginal inhibition)). Ref: J. Kobayashi, et al, JACS, 1984, 106, 1526│ K. L. Rinehart, et al, JACS, 1987, 109, 3378│ M. A. Rashid, et al, JNP, 2001, 64, 1454 HO

Br

N H

N

3.7 β-Carboline Alkaloids

293

837 Eudistomin K Type: β-Carboline alkaloids. C14H16BrN3OS Oil, [α]D25 = −102° (c = 0.2, MeOH). Source: Ascidians Eudistoma gilboverde (Palau, Oceania), Ritterella sigillinoides (New Zealand) and Eudistoma olivaceum (Caribbean Sea). Pharm: Antiviral (HSV-1 assay: 250 ng/12.7 mm disk, + (part inhibition)); antibacterial (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Bacillus subtilis, IZD = 23 mm; Escherichia coli, IZD = 15 mm); antifungal (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Saccharomyces cerevisiae, IZD = 24 mm; Penicillium atrovenetum, IZD = 27 mm). Ref: K. L. Rinehart, Jr., et al, JACS, 1984, 106, 1524│ J. W. Blunt, et al, Tet. Lett., 1987, 28, 1825│ K. L. Rinehart, et al, JACS, 1987, 109, 3378│ J. -J. Liu, et al, JCS Perken I, 2000, 3487│ M. A. Rashid, et al, JNP, 2001, 64, 1454

Br

N H H

N

H 2N

O S

838 Eudistomin L Type: β-Carboline alkaloids. C14H16BrN3OS [α]D25 = −77° (c = 0.2, MeOH). Source: Ascidians Eudistoma olivaceum (Caribbean Sea) and Eudistoma gilboverde (Palau, Oceania). Pharm: Antiviral (HSV-1 assay: 100 ng/12.7 mm disk, + (part inhibition)); antibacterial (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Bacillus subtilis, IZD = 27 mm; Escherichia coli, IZD = 20 mm); antifungal (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Saccharomyces cerevisiae, IZD = 28 mm; Penicillium atrovenetum, IZD = 32 mm). Ref: K. L. Rinehart, Jr., et al, JACS, 1984, 106, 1524│ J. W. Blunt, et al, Tet. Lett., 1987, 28, 1825│ K. L. Rinehart, et al, JACS, 1987, 109, 3378│ J. -J. Liu, et al, JCS Perken I, 2000, 3487│ M. A. Rashid, et al, JNP, 2001, 64, 1454 Br N H H H 2N

N

O S

839 Eudistomin M Type: β-Carboline alkaloids. C15H11N3O Yellow prisms (CHCl3/MeOH). Source: Ascidian Eudistoma olivaceum (Caribbean Sea). Pharm: Antiviral; ATPase stimulant (used as biochemical tool in study of muscular contraction). Ref: J. Kobayashi, et al, JACS, 1984, 106, 1526│ K. L. Rinehart, et al, JACS, 1987, 109, 3378│ P. Molina., Tet. Lett., 1992, 33, 2891

294

3 Pyrrole Indole and Imidazole Alkaloids

HO

N H

N

NH

840 Eudistomin N Type: β-Carboline alkaloids. C11H7BrN2 Yellow needles (MeOH/CHCl3), mp 265–268 °C. Source: Ascidian Eudistoma olivaceum (Caribbean Sea). Pharm: Antibacterial (mixture with Eudistomin O, 100 μg/12.7 mm disk, 37 °C, 20h or 16h, Bacillus subtilis, IZD = 19 mm; Escherichia coli, IZD = 18 mm); antifungal (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Saccharomyces cerevisiae, IZD = 25 mm; Penicillium atrovenetum, IZD = 20 mm). Ref: J. Kobayashi, et al, JACS, 1984, 106, 1526 Br N H

N

841 Eudistomin O Type: β-Carboline alkaloids. C11H7BrN2 Pale-yellow crystal, mp 208–210 °C. Source: Ascidians Eudistoma olivaceum (Caribbean Sea) and Ritterella sigillinoides (New Zealand). Pharm: Antibacterial (mixture with Eudistomin N, 100 μg/12.7 mm disk, 37 °C, 20h or 16h, Bacillus subtilis, IZD = 19 mm; Escherichia coli, IZD = 18 mm); antifungal (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Saccharomyces cerevisiae, IZD = 25 mm; Penicillium atrovenetum, IZD = 20 mm). Ref: J. Kobayashi, et al, JACS, 1984, 106, 1526│ R. J. Lake, et al, Aust. J. Chem., 1989, 42, 1201

Br

N H

N

842 Eudistomin P Type: β-Carboline alkaloids. C15H12N3O mp 128–130 °C. Source: Ascidian Eudistoma olivaceum (Caribbean Sea). Pharm: Antiviral (HSV-1 assay: 500 ng/12.7 mm disk, + (part inhibition)); antibacterial (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Bacillus subtilis, IZD = 15 mm; Escherichia coli, IZD = 0 mm); antifungal (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Saccharomyces cerevisiae, IZD = 20 mm (faint); Penicillium atrovenetum, IZD = 0 mm). Ref: J. Kobayashi, et al, JACS, 1984, 106, 1526│ K. L. Rinehart, et al, JACS, 1987, 109, 3378

3.7 β-Carboline Alkaloids

295

HO Br

N

N H

N

843 Eudistomin Q Type: β-Carboline alkaloids. C15H13N3O mp 120–125 °C. Source: Ascidian Eudistoma olivaceum (Caribbean Sea). Pharm: Antiviral (HSV-1 assay: 500 ng/12.7 mm disk, ± (marginal inhibition)); antibacterial (100 μg/12.7 mm disk, 37 °C, 20h or 16h, Bacillus subtilis, IZD = 14 mm; Escherichia coli, IZD = 0 mm). Ref: J. Kobayashi, et al, JACS, 1984, 106, 1526│ K. L. Rinehart, et al, JACS, 1987, 109, 3378 HO N

N H

N

844 Eudistomin U Type: β-Carboline alkaloids. C19H13N3 mp 92 °C. Source: Ascidian Lissoclinum frafile (Caribbean Sea). Pharm: Antibacterial (Agrobacterium tumfaims, strong); DNA binder (chromatographic purification procedure). Ref: A. Badre, et al, JNP, 1994, 57, 528│ P. Molina, et al, Tetrahedron lett., 1995, 36, 3581│ P. Rocca, et al, Tet. Lett., 1995, 36, 7085 4

3

N N H NH 6'

845 Eudistomin Y1 Type: β-Carboline alkaloids. C18H12N2O2 Source: Ascidian Eudistoma sp. (Korea Waters). Pharm: Antibacterial (Staphylococcus epidermis and Bacillus subtilis). Ref: W. Wang, et al, JNP, 2008, 71, 163

296

3 Pyrrole Indole and Imidazole Alkaloids

N N H

O

HO

846 Eudistomin Y2 Type: β-Carboline alkaloids. C18H11BrN2O2 Source: Ascidian Eudistoma sp. (Korea Waters). Pharm: Antibacterial (Staphylococcus epidermis and Bacillus subtilis). Ref: W. Wang, et al, JNP, 2008, 71, 163 Br N N H

O

HO

847 Eudistomin Y3 Type: β-Carboline alkaloids. C18H11BrN2O2 Source: Ascidian Eudistoma sp. (Korea Waters). Pharm: Antibacterial (Staphylococcus epidermis and Bacillus subtilis). Ref: W. Wang, et al, JNP, 2008, 71, 163

N

Br N H

O

HO

848 Eudistomin Y4 Type: β-Carboline alkaloids. C18H10Br2N2O2 Source: Ascidian Eudistoma sp. (Korea Waters). Pharm: Antibacterial (Staphylococcus epidermis and Bacillus subtilis). Ref: W. Wang, et al, JNP, 2008, 71, 163 Br N N H Br HO

O

3.7 β-Carboline Alkaloids

297

849 Eudistomin Y5 Type: β-Carboline alkaloids. C18H10Br2N2O2 Source: Ascidian Eudistoma sp. (Korea Waters). Pharm: Antibacterial (Staphylococcus epidermis and Bacillus subtilis). Ref: W. Wang, et al, JNP, 2008, 71, 163

N N H

O

Br HO

Br

850 Eudistomin Y6 Type: β-Carboline alkaloids. C18H9Br3N2O2 Source: Ascidian Eudistoma sp. (Korea Waters). Pharm: Antibacterial (Staphylococcus epidermis and Bacillus subtilis). Ref: W. Wang, et al, JNP, 2008, 71, 163 Br N N H

O

Br HO

Br

851 Eudistomin Y7 Type: β-Carboline alkaloids. C18H9Br3N2O2 Source: Ascidian Eudistoma sp. (Korea Waters). Pharm: Antibacterial (Staphylococcus epidermis and Bacillus subtilis). Ref: W. Wang, et al, JNP, 2008, 71, 163

N

Br N H

O

Br HO

Br

852 Fascaplysin Type: β-Carboline alkaloids. C18H11N2O1+ Red cryst. (MeOH or CHCl3) (chloride), mp 232–235 °C (chloride). Source: Sponges Fascaplysinopsis sp., Hyrtios cf. erecta and Smenospongia sp., ascidian Didemnum sp. Pharm: CDK4 inhibitor (selective, IC50 = 0.35 μmol/L); cytotoxic; antibacterial (Staphylococcus aureus, 0.1 μg/desk, IZD = 15 mm;

298

3 Pyrrole Indole and Imidazole Alkaloids

Escherichia coli, 5 μg/desk, IZD = 8 mm; Candida albicans, 1 μg/desk, IZD = 11 mm) antifungal (microzyme, 0.1 μg/desk, IZD = 20 mm); cytotoxic (L1210, IC50 = 0.2 μg/mL); HIV-1-rt inhibitor (0.12 mmol/L, to 10% residual activity) (Kirsch, 2000); p56lck tyrosine kinase inhibitor (0.7 mmol/L, reduced to 10%) (Kirsch, 2000); antiplasmodial (Plasmodium falciparum strain K1, IC50 = 50 ng/mL, control Chloroquine, IC50 = 54 ng/mL, control Artemisinine, IC50 = 1 ng/mL; chloroquine-susceptible Plasmodium falciparum strain NF54, IC50 = 34 ng/mL, Chloroquite, IC50 = 4 ng/mL, Artemisinine, IC50 = 2 ng/mL) (Kirsch, 2000); cytotoxic (rat skeletal muscle myoblast L-6 cells, MIC = 2.5 μg/mL) (Kirsch, 2000); antiplasmodial life stage-specific activity (Plasmodium falciparum strain W2-Mef, All live parasites, IC50 = 48.2 nmol/L, Chloroquite, IC50 = 149 nmol/L, Artermisinin, IC50 = 6.245 nmol/L; Rings stage, IC50 = 7.82 nmol/L, Chloroquite, IC50 = 174 nmol/L, Artermisinin, IC50 = 5.92 nmol/L; Trophozoites stage, IC50 = 401 nmol/L, Chloroquite, IC50 = 162 nmol/L, IC50 = 6.46 nmol/L; Schizonts stage, IC50 = 65.2 nmol/L, Chloroquite, IC50 = 80 nmol/L, Artermisinin, IC50 = 5.91 nmol/L); antitrypanosomal (Trypanosoma brucei subsp. rhodesiense, IC50 = 0.17 μg/mL (630 nmol/L)) (Kirsch, 2000). Ref: D. M. Roll, et al, JOC, 1988, 53, 3276│ R. Soni, et al, Biochem. Biophys. Res. Commun. 2000, 275, 877│ G. Kirsch, et al, JNP, 2000, 63, 825│ Z. Lu, et al, BoMC, 2011, 19, 6604│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) H

O

N 10 3

N

+

853 Gesashidine A Type: β-Carboline alkaloids. C18H19N4OS Source: Sponge Thorectidae sp. SS-1035 (Okinawa). Pharm: Antibacterial (Micrococcus luteus). Ref: Y. Iinuma, et al, JNP, 2005, 68, 1109 N

N N

HO N H

+

S

854 Hainanerectamine C Type: β-Carboline alkaloids. C16H16N4O3 Source: Sponge Hyrtios erectus (Hainan). Pharm: Inhibitor of serine/threonine kinase Aurora A (IC50 = 18.6 μg/mL, involved in cell division regulation). Ref: W. -F. He, et al, Mar. Drugs, 2014, 12, 3982

3.7 β-Carboline Alkaloids

299

O OH NH

HO

N N H

NH

855 Harman 1-Methyl-β-carboline Type: β-Carboline alkaloids. C12H10N2 mp 237–238 °C, mp 228 °C. Source: Bryozoans Costaticella hastate and Cribricellina cribraria (New Zealand). Pharm: Cytotoxic (P388, IC50 = 25000 ng/mL); antibacterial (Escherichia coli, MIC = 60–120 μg/disc; Bacillus subtilis, MIC = 7.5–15 μg/disc; Pseudomonas aeruginosa, MIC > 60 μg/disc); antifungal (Candida albirnns, MIC = 1.9–3.8 μg/disc; Trichophyton mentagropbytes, MIC = 3.7–7.5 μg/disc; Cladzspwum resina, MIC = 15–30 μg/disc); sedative; hallucinogen; plant growth and enzyme inhibitor. Ref: A. J. Blackman, et al, JNP, 1987, 50, 494│ M. R. Prinsep, et al, JNP, 1991, 54, 1068

N H

N

856 Homofascaplysin A Type: β-Carboline alkaloids. C21H17N2O21+ Brown oil. Source: Sponges Hyrtios cf. erecta and Fascaplysinopsis reticulata, ascidian Didemnum sp. (Pratt Reef, Fiji). Pharm: Antiplasmodial (Plasmodium falciparum strain K1, IC50 = 14 ng/mL, control Chloroquine, IC50 = 54 ng/mL, control Artemisinine, IC50 = 1 ng/mL; chloroquine-susceptible Plasmodium falciparum strain NF54, IC50 = 24 ng/mL, Chloroquite, IC50 = 4 ng/mL, Artemisinine, IC50 = 2 ng/mL) (Kirsch, 2000); cytotoxic (rat skeletal muscle myoblast L-6 cells, MIC = 1.1 μg/mL, mouse peritoneal macrophages, MIC = 30 μg/mL) (Kirsch, 2000); antiplasmodial life stage-specific activity (Plasmodium falciparum strain W2-Mef, All live parasites, IC50 = 105 nmol/L, Chloroquite, IC50 = 149 nmol/L, Artermisinin, IC50 = 6.245 nmol/L; Rings stage, IC50 = 0.55 nmol/L, Chloroquite, IC50 = 174 nmol/L, Artermisinin, IC50 = 5.92 nmol/L; Trophozoites stage, IC50 = 252 nmol/L, Chloroquite, IC50 = 162 nmol/L, Artermisinin, IC50 = 6.46 nmol/L; Schizonts stage, IC50 = 94 nmol/L, Chloroquite, IC50 = 80 nmol/L, Artermisinin, IC50 = 5.91 nmol/L); antibacterial (Escherichia coli, 50 μg/9 mm and Bacillus megaterium, 50 μg/11 mm) (Kirsch, 2000); p56lck tyrosine kinase inhibitor (reduced to 8% at 0.6 mmol, and to 44% at 0.3 mmol/L) (Kirsch, 2000). Ref: C. Jiménez, et al, JOC, 1991, 56, 3403│ G. Kirsch, et al, JNP, 2000, 63, 825│ Z. Lu, et al, BoMC, 2011, 19, 6604

300

3 Pyrrole Indole and Imidazole Alkaloids

N

+

N H HO

O

857 8-Hydroxy-1-vinyl-β-carboline Type: β-Carboline alkaloids. C13H10N2O Yellow oil. Source: Bryozoans Cribricellina cribraria (New Zealand) and Catenicella cribraria (major, Australia). Pharm: Cytotoxic (NCI hmn tumour 60-cell-line assay, GI50 = 1.8 μmol/L, TGI = 5.8 μmol/L, LC50 = 19 μmol/L); cytotoxic (P388, IC50 = 100 ng/mL); antiviral/cytotoxic (0.5 μg/disc: HSV-1 virus grown on BSC, zone 1–2 mm excess radius from disc edge; PV-1 (Polio virus, Pfizer vacine strain) grown on BSC cell line, zone 1–2 mm excess radius from disc edge; BSC, zone 2–4 mm excess radius from disc edge); antibacterial (Escherichia coli, MIC > 60 μg/disc; Bacillus subtilis, MIC = 7.5–15 μg/disc; Pseudomonas aeruginosa, MIC > 60 μg/disc); antifungal (Candida albirnns, MIC = 15–30 μg/disc; Trichophyton mentagropbytes, MIC = 0.45–0.9 μg/disc; Cladzspwum resina, MIC = 3.7–7.5 μg/disc). Ref: M. R. Prinsep, et al, JNP, 1991, 54, 1068│ J. A. Beutler, et al, JNP, 1993, 56, 1825

OH

N

N H

858 Hyrtiocarboline Type: β-Carboline alkaloids. C16H10N4O4 Orange oil. Source: Sponge Hyrtios reticulatus (Bismarck Sea, Papua New Guinea). Pharm: Cytotoxic (selectively antiproliferative). Ref: W. D. Inman, et al, JNP, 2010, 73, 255 O HO

OH N

N H

10

H N

O N

859 Hyrtioerectine D Type: β-Carboline alkaloids. C20H13N3O4 Yellow solid. Source: Sponge Hyrtios sp. (Red Sea). Pharm: Cytotoxic (MDA-MB-231, GI50 = 25 μmol/L, positive antiproliferative control Doxorubicin, GI50 = 0.30 μmol/L; A549, GI50 = 30 μmol/L, Doxorubicin, GI50 = 0.35 μmol/L; HT29, GI50 = 28 μmol/L, Doxorubicin, GI50 = 0.40 μmol/L); antioxidant (DPPH scavenger, InRt = 45%); antifungal (Candida

3.7 β-Carboline Alkaloids

301

albicans, inhibition zone = 17 mm, control Clotrimazole, inhibition zone = 35 mm); antibacterial (Staphylococcus aureus, inhibition zone = 20 mm, control Ampicillin, inhibition zone = 30 mm; Pseudomonas aeruginosa inhibition zone = 7–9 mm, control Imipenem, inhibition zone = 30 mm; Escherichia coli, inactive). Ref: D. T. A. Youssef, et al, Mar. Drugs, 2013, 11, 1061

O

H N

OH

OH

HO N N H

860 Hyrtioerectine E Type: β-Carboline alkaloids. C21H15N3O4 Yellow solid. Source: Sponge Hyrtios sp. (Red Sea). Pharm: Cytotoxic (MDA-MB-231, GI50 = 90 μmol/L, positive antiproliferative control Doxorubicin, GI50 = 0.30 μmol/L; A549, GI50 = 100 μmol/L, Doxorubicin, GI50 = 0.35 μmol/L; HT29, GI50 = 85 μmol/L, Doxorubicin, GI50 = 0.40 μmol/L); antioxidant (DPPH scavenger, InRt = 31%); antifungal (Candida albicans, inhibition zone = 9 mm, control Clotrimazole, inhibition zone = 35 mm); antibacterial (Staphylococcus aureus, inhibition zone = 10 mm, control Ampicillin, inhibition zone = 30 mm; Pseudomonas aeruginosa inhibition zone = 7–9 mm, control Imipenem, inhibition zone = 30 mm; Escherichia coli, inactive). Ref: D. T. A. Youssef, et al, Mar. Drugs, 2013, 11, 1061

O

H N

OH

OH

O N N H

861 Hyrtioerectine F Type: β-Carboline alkaloids. C20H14N4O3 Yellow solid. Source: Sponge Hyrtios sp. (Red Sea). Pharm: Cytotoxic (MDA-MB-231, GI50 = 42 μmol/L, positive antiproliferative control Doxorubicin, GI50 = 0.30 μmol/L; A549, GI50 = 35 μmol/L, Doxorubicin, GI50 = 0.35 μmol/L; HT29, GI50 = 45 μmol/L, Doxorubicin, GI50 = 0.40 μmol/L); antioxidant (DPPH scavenger, InRt = 42%); antifungal (Candida albicans, inhibition zone = 14 mm, control Clotrimazole, inhibition zone = 35 mm); antibacterial (Staphylococcus aureus, inhibition zone = 16 mm, control Ampicillin, inhibition zone = 30 mm; Pseudomonas aeruginosa inhibition zone = 7–9 mm, control Imipenem, inhibition zone = 30 mm; Escherichia coli, inactive). Ref: D. T. A. Youssef, et al, Mar. Drugs, 2013, 11, 1061

302

3 Pyrrole Indole and Imidazole Alkaloids

NH2

O

H N OH

HO N N H

862 Hyrtiomanzamine Type: β-Carboline alkaloids. C18H17N4O2S1+ Orange glassy solid. Source: Sponge Hyrtios erecta (Red Sea). Pharm: Immunosuppressive (B lymphocytes reaction assay, EC50 = 2 μg/mL). Ref: D. B. Stierle, et al, JOC, 1980, 45, 4980 OH N

N H

N N

O +

S

863 Hyrtioreticulin B Type: β-Carboline alkaloids. C16H16N4O3 Source: Sponge Hyrtios reticulatus (N. Sulawesi, Indonesia). Pharm: Inhibitor of ubiquitin-activating enzyme E1. Ref: R. Yamanokuchi,et al, BoMC, 2012, 20, 4437│ K. Imada, et al, Tetrahedron, 2013, 69, 7051 COOH HO

NH N N H

H

NH

864 Hyrtioreticulin E Type: β-Carboline alkaloids. C13H14N2O3 Source: Sponge Hyrtios reticulatus (N. Sulawesi, Indonesia). Pharm: Inhibitor of ubiquitin-activating enzyme E1. Ref: R. Yamanokuchi,et al, BoMC, 2012, 20, 4437│ K. Imada, et al, Tetrahedron, 2013, 69, 7051 COOH HO

NH N H

3.7 β-Carboline Alkaloids

303

865 Isoeudistomin U Eudisin B Type: β-Carboline alkaloids. C19H15N3 Yellow foam. Source: Ascidian Lissoclinum fragile (Caribbean Sea). Pharm: Antibacterial (Agrobacterium tumfaims, strong); DNA binder (chromatographic purification procedure). Ref: A. Badre, et al, JNP, 1994, 57, 528│ G. Massiot, et al, JNP, 1995, 58, 1636 4

3

N

N H

N H

866 Manzamine C Type: β-Carboline alkaloids. C23H29N3 Plates (CHCl3/MeCN), mp 77–82 °C. Source: Sponge Haliclona sp. Pharm: Antituberculosis (Mycobacterium tuberculosis H37Rv); cytotoxic. Ref: R. Sakai, et al, Tetrahedron, Lett., 1987, 28, 5493│ H. Seki, et al, CPB, 1993, 41, 1173

N

N H

N

867 Marinacarboline A Type: β-Carboline alkaloids. C23H21N3O3 Yellowish needles. Source: Marine-derived bacterium Marinactinospora thermotolerans SCSIO 00652 (sediment, South China Sea, China). Pharm: Antiplasmodial (Plasmodium falciparum lines 3D7 Drugsensitive line, IC50 = 36.03 μmol/L, control chloroquine, IC50 = 0.0128 μmol/L; Dd2 Multi-drug-resistant line, IC50 = 1.92 μmol/L, chloroquine, IC50 = 0.0974 μmol/L). Ref: H. Huang, et al, JNP, 2011, 74, 2122 O O H N

N

H N O

868 Marinacarboline B Type: β-Carboline alkaloids. C22H19N3O3 Yellowish solid. Source: Marine-derived bacterium Marinactinospora thermotolerans SCSIO 00652 (sediment, South China Sea, China). Pharm: Antiplasmodial (Plasmodium falciparum lines 3D7 Drugsensitive line, IC50 = 16.65 μmol/L, control chloroquine, IC50 = 0.0128 μmol/L; Dd2

304

3 Pyrrole Indole and Imidazole Alkaloids

Multi-drug-resistant line, IC50 = 15.59 μmol/L, chloroquine, IC50 = 0.0974 μmol/L). Ref: H. Huang, et al, JNP, 2011, 74, 2122 OH O H N

N

H N O

869 Marinacarboline C Type: β-Carboline alkaloids. C22H19N3O2 Yellowish solid. Source: Marine-derived bacterium Marinactinospora thermotolerans SCSIO 00652 (sediment, South China Sea, China). Pharm: Antiplasmodial (Plasmodium falciparum lines 3D7 Drugsensitive line, IC50 = 3.09 μmol/L, control chloroquine, IC50 = 0.0128 μmol/L; Dd2 Multi-drug-resistant line, IC50 = 3.38 μmol/L, chloroquine, IC50 = 0.0974 μmol/L). Ref: H. Huang, et al, JNP, 2011, 74, 2122 O H N

N

H N O

870 Marinacarboline D Type: β-Carboline alkaloids. C24H20N4O2 Yellowish solid. Source: Marine-derived bacterium Marinactinospora thermotolerans SCSIO 00652 (sediment, South China Sea, China). Pharm: Antiplasmodial (Plasmodium falciparum lines 3D7 Drugsensitive line, IC50 = 5.39 μmol/L, control chloroquine, IC50 = 0.0128 μmol/L; Dd2 Multi-drug-resistant line, IC50 = 3.59 μmol/L, chloroquine, IC50 = 0.0974 μmol/L). Ref: H. Huang, et al, JNP, 2011, 74, 2122 H N

O H N

N

H N O

871 N14-Methyleudistomidin C Type: β-Carboline alkaloids. C16H18BrN3OS Yellowish gum, [α]D = +12.9° (c = 0.07, MeOH). Source: Ascidian Eudistoma gilboverde. Pharm: Cytotoxic (LOX, IC50 = 0.41 μg/mL; OVCAR-3, IC50 = 0.98 μg/mL; Colon205, IC50 = 0.42 μg/mL; Molt4, IC50 = 0.57 μg/mL). Ref: M. A. Rashid, et al, JNP, 2001, 64, 1454

3.7 β-Carboline Alkaloids

305

Br HO N H

N 14

S

N

872 N2-Methyleudistomin D Type: β-Carboline alkaloids. C12H10BrN2O1+ Amorph. yellow powder. Source: Ascidian Eudistoma gilboverde (Palau, Oceania). Pharm: Cytotoxic (melanoma LOX, IC50 = 15.0 μg/mL; ovarian OVCAR-3, IC50 = 20.0 μg/mL; colon Colon205, IC50 = 19.1 μg/mL; leukemia Molt4, IC50 = 16.6 μg/mL). Ref: M. A. Rashid, et al, JNP, 2001, 64, 1454 Br N

HO

+

N H

873 N2-Methyleudistomin J Type: β-Carboline alkaloids. C12H10BrN2O1+ Yellow gum. Source: Ascidian Eudistoma gilboverde. Pharm: Cytotoxic (LOX, IC50 = 15.1 μg/mL; OVCAR-3, IC50 = 20.0 μg/mL; Colon205, IC50 = 15.1 μg/mL; Molt4, IC50 = 17.5 μg/mL). Ref: M. A. Rashid, et al, JNP, 2001, 64, 1454 HO

Br

N

N H

+

874 2-Methyl-9H-pyrido[3,4b]indole-3-carboxylic acid Type: β-Carboline alkaloids. C13H10N2O2 Pale yellow solid, mp 203–205 °C. Source: Soft coral Lignopsis spongiosum (South Georgia I.). Pharm: Antibacterial (agar diffusion assay, Escherichia coli ATCC 25922, 50 μg/disk, IZD = 11 mm). Ref: G. M. Cabrera, et al, JNP, 1999, 62, 759 O –

O N H

N

+

875 Milnamide A Type: β-Carboline alkaloids. C31H46N4O4 Amorph. solid, [α]D27 = +28.8° (c = 0.5, CH2Cl2). Source: Sponge Auletta cf. constricta (Papua New Guinea). Pharm: Cytotoxic

306

3 Pyrrole Indole and Imidazole Alkaloids

(A549, IC50 = 4.1 μg/mL; HT29, IC50 = 2.8 μg/mL; B16/F10, IC50 = 3.3 μg/mL; P388, IC50 = 0.74 μg/mL). Ref: P. Crews, et al, JOC, 1994, 59, 2932 O H N

N

O

OH N H

N O

876 Opacaline A Type: β-Carboline alkaloids. C16H20BrN52+ Yellow oil. Source: Ascidian Pseudodistoma opacum (Auckland, New Zealand). Pharm: Antitrypanosomal (Trypanosoma brucei rhodesience, IC50 = 30 μmol/L, control Melarsoprol, IC50 = 0.005 μmol/L; Trypanosoma cruzi, IC50 = 86 μmol/L, control Benznidazole, IC50 = 1.8 μmol/L; Leishmania donovani, IC50 > 130 μmol/L, control Miltefosine, IC50 = 0.53 μmol/L; Plasmodium falciparum K1, IC50 = 2.5 μmol/L, control Chloroquine, IC50 = 0.28 μmol/L); cytotoxic (L-6 rat skeletal myoblast cell line, IC50 = 79 μmol/L, control Podophyllotoxin, IC50 = 0.019 μmol/L). Ref: S. T. S. Chan, et al, JNP, 2011, 74, 1972 + N H

H Br

N H

N H

+ N H

NH2

877 Opacaline B Type: β-Carboline alkaloids. C16H20BrN5O2+ Yellow oil. Source: Ascidian Pseudodistoma opacum (Auckland, New Zealand). Pharm: Antitrypanosomal (Trypanosoma brucei rhodesience, IC50 = 27 μmol/L, control Melarsoprol, IC50 = 0.005 μmol/L; Trypanosoma cruzi, IC50 = 107 μmol/L, control Benznidazole, IC50 = 1.8 μmol/L; Leishmania donovani, IC50 > 101 μmol/L, control Miltefosine, IC50 = 0.53 μmol/L; Plasmodium falciparum K1, IC50 = 4.5 μmol/L, control Chloroquine, IC50 = 0.28 μmol/L); cytotoxic (L-6 rat skeletal myoblast cell line, IC50 = 120 μmol/L, control Podophyllotoxin, IC50 = 0.019 μmol/L). Ref: S. T. S. Chan, et al, JNP, 2011, 74, 1972 + N H

H Br

+ N H

N OH

N H

NH2

3.7 β-Carboline Alkaloids

307

878 6-Oxofascaplysin Type: β-Carboline alkaloids. C18H10N2O3 Source: Sponge Hyrtios sp. (Australia). Pharm: Cytotoxic (LNCaP and NFF cell lines, weak). Ref: S. Khokhar, et al, BoMCL, 2014, 24, 3329 O N

HO N H

O

879 Pavettine 1-Vinyl-β-carboline Type: β-Carboline alkaloids. C13H10N2 Source: Bryozoans Cribricellina cribraria (New Zealand) and Costaticella hastata. Pharm: Cytotoxic (P388, IC50 = 100 ng/mL); antiviral/cytotoxic (0.5 μg/disc: HSV-1 virus grown on BSC, zone 1–2 mm excess radius from disc edge; PV-1 (Poliovirus, Pfizer vacine strain) grown on BSC cell line, zone 1–2 mm excess radius from disc edge; BSC, zone 2–4 mm excess radius from disc edge); antibacterial (Escherichia coli, MIC = 30–60 μg/disc; Bacillus subtilis, MIC = 1.9–3.8 μg/disc; Pseudomonas aeruginosa, MIC > 60 μg/disc); antifungal (Candida albirnns, MIC = 1.9–3.8 μg/disc; Trichophyton mentagropbytes, MIC = 0.1–0.2 μg/disc; Cladzspwum resina, MIC = 0.9–1.9 μg/disc). Ref: A. J. Blackman, et al, JNP, 1987, 50, 494│ M. R. Prinsep, et al, JNP, 1991, 54, 1068

N

N H

880 Penipaline A Type: β-Carboline alkaloids. C17H20N2O2 Source: Deep-sea fungus Penicillium paneum SD-44 (sediment, cultivated in a 500 L bioreactor). Pharm: Cytotoxic (A549, IC50 = 20.4–21.5 μmol/L; HCT116, IC50 = 14.9–18.5 μmol/L for five compounds from the paper). Ref: C. Li, et al, Helv. Chim. Acta, 2014, 97, 1440 O OH NH N H

881 Penipaline B Type: β-Carboline alkaloids. C19H24N2O2 Source: Deep-sea fungus Penicillium paneum SD-44 (sediment, cultivated in a 500 L bioreactor). Pharm: Cytotoxic (A549,

308

3 Pyrrole Indole and Imidazole Alkaloids

IC50 = 20.4–21.5 μmol/L; HCT116, IC50 = 14.9–18.5 μmol/L for five compounds from the paper). Ref: C. Li, et al, Helv. Chim. Acta, 2014, 97, 1440 O OH NH N H

882 Plakortamine A Type: β-Carboline alkaloids. C15H16BrN3 Pale yellow oil. Source: Sponge Plakortis nigra (Palau, depth of 380 ft, yield = 0.61% dw). Pharm: Cytotoxic (HCT116, IC50 = 3.2 μmol/L). Ref: J. S. Sandler, et al, JNP, 2002, 65, 1258

Br

N

N

H

N

883 Plakortamine B Type: β-Carboline alkaloids. C13H9BrN2 Yellow oil. Source: Sponge Plakortis nigra (Palau, depth of 380 ft, yield = 0.063% dw). Pharm: Cytotoxic (HCT116, IC50 = 0.62 μmol/L). Ref: J. S. Sandler, et al, JNP, 2002, 65, 1258

Br

N

N

H

884 Plakortamine C Type: β-Carboline alkaloids. C27H23Br2N5 Pale yellow gum. Source: Sponge Plakortis nigra (Palau, depth of 380 ft, yield = 0.021% dw). Pharm: Cytotoxic (HCT116, IC50 = 2.15 μmol/L). Ref: J. S. Sandler, et al, JNP, 2002, 65, 1258

Br

N H

N

N N

N

Br

H

885 Plakortamine D Type: β-Carboline alkaloids. C15H14BrN3O Pale yellow oil, [α]D = −2.1° (c = 0.6, MeOH). Source: Sponge Plakortis nigra (Palau, depth of 380 ft, yield = 0.027% dw). Pharm: Cytotoxic (HCT116, IC50 = 15 μmol/L). Ref: J. S. Sandler, et al, JNP, 2002, 65, 1258

3.7 β-Carboline Alkaloids

Br

N

N H

309

O N

886 Secofascaplysic acid Type: β-Carboline alkaloids. C18H12N2O4 Source: Sponge Hyrtios sp. (Australia). Pharm: Cytotoxic (LNCaP and NFF cell lines, weak). Ref: S. Khokhar, et al, BoMCL, 2014, 24, 3329 O HO N

HO

O

N H

887 1,2,3,4-Tetrahydro-1,1-dimethyl-β-carboline-3β-carboxylic acid Type: β-Carboline alkaloids. C14H16N2O2 Source: Deep-sea fungus Penicillium paneum SD-44 (sediment, cultivated in a 500 L bioreactor). Pharm: Cytotoxic (A549, IC50 = 20.4–21.5 μmol/L; HCT116, IC50 = 14.9–18.5 μmol/L for five compounds from the paper). Ref: C. Li, et al, Helv. Chim. Acta, 2014, 97, 1440 O OH NH N H

888 Tiruchanduramine Type: β-Carboline alkaloids. C16H16N6O Source: Ascidian Synoicum macroglossum (India waters). Pharm: α-Glucosidase inhibitor (IC50 = 78.2 μg/mL). Ref: K. Ravinder, et al, Tet. Lett., 2005, 46, 5475 O N H N

NH N H

NH

N H

889 Villagorgin A Type: β-Carboline alkaloids. C16H16N4 Red amorph. solid, [α]D20 = +7.8°. Source: Gorgonian Villogorgia rubra (New Caledonia). Pharm: Calmodulin antagonist. Ref:

310

3 Pyrrole Indole and Imidazole Alkaloids

A. Espada, et al, Tet. Lett., 1993, 34, 7773│ R. M. Grazul, et al, Nat. Prod. Lett., 1994, 5, 187

N H H

N

NH N

890 Xestomanzamine A Type: β-Carboline alkaloids. C16H12N4O Yellow needles (CHCl3/MeOH), mp 185–186 °C. Source: Sponge Xestospongia sp. (Japan waters). Pharm: Cytotoxic. Ref: M. Kobayashi, et al, Tetrahedron, 1995, 51, 3727 4 3

N

N H

O N

N

891 Xestomanzamine B Type: β-Carboline alkaloids. C16H14N4O Yellow oil. Source: Sponge Xestospongia sp. (Japan waters). Pharm: Cytotoxic (KB, 1C50 = 14.0 μg/mL). Ref: M. Kobayashi, et al, Tetrahedron, 1995, 51, 3727│ B. E. A. Burm, et al, Heterocycles, 2001, 55, 495 4 3

N

N H

O N

N

3.8 Manzamines 892 Acantholactam Type: Manzamines. C36H42N4O4 Source: Sponge Acanthostrongylophora ingens (Indonesia). Pharm: Inhibits accumulation of cholesterol esters (in macrophages). Ref: A. H. El-Desoky, et al, JNP, 2014, 77, 1536

3.8 Manzamines

N

311

N H

H

OH

N

N O O

OH

893 Acanthomanzamine A Type: Manzamines. C34H47N3O3 Source: Sponge Acanthostrongylophora ingens. Pharm: Cytotoxic (HeLa, IC50 = 4.2 μmol/L); proteasome inhibitor (IC50 = 4.1 μmol/L); inhibitor of accumulation of cholesterol ester (in macrophages, 20 μmol/L, InRt = 48%). Ref: A. Furusato, et al, Org. Lett.,2014, 16, 3888 OH HN H

OH

H OH

N H

N

894 Acanthomanzamine B Type: Manzamines. C34H47N3O3 Source: Sponge Acanthostrongylophora ingens. Pharm: Cytotoxic (HeLa, IC50 = 5.7 μmol/L); proteasome inhibitor (IC50 = 7.8 μmol/L); inhibitor of accumulation of cholesterol ester (in macrophages, 20 μmol/L, InRt = 73%). Ref: A. Furusato, et al, Org. Lett., 2014, 16, 3888 OH HN H

OH

H OH

N H

N

312

3 Pyrrole Indole and Imidazole Alkaloids

895 Acanthomanzamine D Type: Manzamines. C37H46N4O Source: Sponge Acanthostrongylophora ingens. Pharm: Cytotoxic (HeLa, IC50 = 15 μmol/L); proteasome inhibitor (IC50 = 0.63 μmol/L); inhibitor of accumulation of cholesterol ester (in macrophages, 20 μmol/L, InRt = 73%). Ref: A. Furusato, et al, Org. Lett., 2014, 16, 3888

N

N H

H N

O N

896 Acanthomanzamine E Type: Manzamines. C38H48N4O Source: Sponge Acanthostrongylophora ingens. Pharm: Cytotoxic (HeLa, IC50 > 20 μmol/L); proteasome inhibitor (IC50 = 1.5 μmol/L); inhibitor of accumulation of cholesterol ester (in macrophages, 20 μmol/L, InRt = 61%). Ref: A. Furusato, et al, Org. Lett., 2014, 16, 3888

N

N H

H N

O N

897 6-Deoxymanzamine X Type: Manzamines. C36H44N4O2 Pale yellow amorph. powder, [α]D = +30° (c = 0.35, CHCl3). Source: An unidentified sponge (order Haplosclerida, family Petrosiidae, Indo-Pacific, yield = 0.0021% dw), sponge Xestospongia ashmorica (Philippines). Pharm: Antileishmanial (Leishmania donovani); antituberculosis (Mycobacterium tuberculosis H37Rv, strong); cytotoxic (L5178, ED50 = 1.8 μg/mL). Ref: R. A. Edrada, et al, JNP, 1996, 59, 1056│ K. A. El Sayed, et al, JACS, 2001, 123, 1804

3.8 Manzamines

N

313

N H

H

OH

N N O

898 3,4-Dihydro-6-hydroxy-10,11-epoxymanzamine A Type: Manzamines. C36H46N4O2 Source: Sponge Amphimedon sp. (Okinawa). Pharm: Cytotoxic (P388, L1210 and KB). Ref: Y. Takahashi, et al, Org. Lett., 2009, 11, 21│ M. Yamada, et al, Tetrahedron, 2009, 65, 2313; 6263 (corrigendum)

N

N H H

O OH

N

H

N

899 3,4-Dihydromanzamine A 3,4-Dihydrokeramamine A Type: Manzamines. C36H46N4O Amorph. solid, mp 237– 241 °C, [α]D20 = +86° (c = 0.25, CHCl3). Source: Sponge Amphimedon sp. (Kerama I., Okinawa). Pharm: Cytotoxic (L1210 and KB); antituberculosis (Mycobacterium tuberculosis H37Rv, strong). Ref: J. Kobayashi, et al, JNP, 1994, 57, 1737│ CRC Press, DNP in DVD, 2012, version 20.2

N

N H

H

OH

N N H

314

3 Pyrrole Indole and Imidazole Alkaloids

900 3,4-Dihydromanzamine A N-oxide Manzamine J N-oxide Type: Manzamines. C36H46N4O2 Yellow crystalline powder, [α]D = +34.1° (c = 0.59, CHCl3). Source: Sponge Xestospongia ashmorica (Philippines). Pharm: Antibacterial; cytotoxic (L5178, ED50 = 1.6 μg/mL). Ref: R. A. Edrada, et al, JNP, 1996, 59, 1056

N

N H H

+

–

O

OH

N

H

N

901 3,4-Dihydromanzamine J N-oxide Type: Manzamines. C36H48N4O2 Pale yellow solid, [α]D23 = +115.5° (c = 0.2, CHCl3). Source: Sponge Amphimedon sp. (Seragaki, Okinawa). Pharm: Cytotoxic (P388, L1210 and KB); antitrypanosomal (Trypanosoma brucei brucei); antiplasmodial (Plasmodium falciparum). Ref: Y. Takahashi, et al, Org. Lett., 2009, 11, 21│ M. Yamada, et al, Tetrahedron, 2009, 65, 2313; 6263 (corrigendum)

N

N H H

+ –

O

OH

N HN

902 10,11,15,16,32,33-Hexahydro-8-hydroxymanzamine A Type: Manzamines. C36H50N4O2 Source: An unidentified sponge (order Haplosclerida family Petrosiidae, Indo-Pacific). Pharm: Anti-inflammatory (modulation of LPSactivated brain microglia in vitro, IC50 (apparent) = 1.97 μmol/L, MMOA: TXB2 inhibition). Ref: K. A. El Sayed, et al, JNP, 2008, 71, 300

3.8 Manzamines

315

6 2

N

8

N H H

H

12

N

OH

OH

35

N

H 34 31

903 8-Hydroxymanzamine A Manzamine G Type: Manzamines. C36H44N4O2 Pale yellow cryst., mp 230 °C (dec), [α]D = +118.5° (c = 1.94, CHCl3). Source: Sponge of family Petrosiidae (Sulawesi, Indonesia), sponges Pachypellina sp. (Indonisia) and Acanthostrongylophora sp. (Indonesia), Pharm: Antimalarial (Plasmodium berghei, in vivo, ip dose 100 μmol/kg, potent and no apparent toxicity); anti-HSV-2; antileishmanial (Leishmania donovani); antituberculosis (Mycobacterium tuberculosis, MIC = 0.4–5.2 μg/mL), cytotoxic (P388, IC50 > 20 μg/mL). Ref: T. Ichiba, et al, JNP, 1994, 57, 168│ K. A. El Sayed, et al, JACS, 2001, 123, 1804│ K .V. Rao, JNP, 2006, 69, 1034

N

N H

H

OH

OH

N H

N

904 ent-8-Hydroxymanzamine A ent-Manzamine G; 8-Hydroxymanzamine J Type: Manzamines. C36H44N4O2 Yellowish powder (EtOH), mp 196–198 °C (dec), [α]D25 = −112° (c = 0.12, CHCl3). Source: An unidentified sponge (order Haplosclerida, family Petrosiidae, IndoPacific, yield = 1.24% dw), sponge Acanthostrongylophora sp. Pharm: Anti-inflammatory (modulation of LPS-activated brain microglia in vitro, IC50 (apparent) < 0.1 μmol/L, MMOA: TXB2 inhibition); anti-toxoplasma (in vitro, Toxoplasma gondii, 1 μmol/L, InRt = 71% with host cell InRt = 38%); antimalarial (in vivo, strong); antituberculosis (Mycobacterium tuberculosis H37Rv, MIC < 12.5 μg/mL, InRt = 98– 99%, strong); cytotoxic (P388, IC50 = 0.25 μg/mL). Ref: K. A. El Sayed, et al, JACS, 2001, 123, 1804│ M. Yousaf, et al, JMC, 2004, 47, 3512│ K. V. Rao, et al, JNP, 2004, 67, 1314│ K. V. Rao, et al, JNP, 2006, 69, 1034│ K. A. El Sayed, et al, JNP, 2008, 71, 300

316

3 Pyrrole Indole and Imidazole Alkaloids

8

N

OH

N H

H

OH

N

N H

905 6-Hydroxymanzamine A Manzamine Y Type: Manzamines. C37H47N4O2 Yellowish amorph. solid, mp 253 °C, [α]D20 = +139° (c = 1.1, MeOH), [α]D19 = +33.2° (c = 2.50, CHCl3). Source: Sponges Amphimedon sp. (Kerama I., Okinawa) and Haliclona sp. Pharm: Cytotoxic (KB, 1C50 = 7.3 μg/mL; L1210); antituberculosis (Mycobacterium tuberculosis H37Rv, strong); antiplasmodial (Plasmodium falciparum D6 and W2, IC50 = 0.4–0.85 μg/mL). Ref: J. Kobayashi, et al, JNP, 1994, 57, 1737│ M. Kobayashi, et al, Tetrahedron, 1995, 51, 3727│ K .V. Rao, et al, JNP, 2006, 69, 1034│ CRC Press, DNP in DVD, 2012, version 20.2 OH 6

N

N H

H

OH

N

N H

906 8-Hydroxymanzamine B Type: Manzamines. C36H46N4O2 Source: Sponge Acanthostrongylophora sp. (Indonesia). Pharm: Antituberculosis (Mycobacterium tuberculosis, MIC = 0.4–5.2 μg/mL). Ref: M. Yousaf, et al, JMC, 2004, 47, 3512│ K. V. Rao, et al, JNP, 2004, 67, 1314│ K. V. Rao, et al, JNP, 2006, 69, 1034

3.8 Manzamines

317

6 2

N

8

N H H

H N

OH

O

12 35

HN 34 31

907 6-Hydroxymanzamine E Type: Manzamines. C36H44N4O3 Source: Sponge Acanthostrongylophora sp. (Indonesia). Pharm: Antituberculosis (Mycobacterium tuberculosis, MIC = 0.4–5.2 μg/mL). Ref: M. Yousaf, et al, JMC, 2004, 47, 3512│ K. V. Rao, et al, JNP, 2004, 67, 1314│ K. V. Rao, et al, JNP, 2006, 69, 1034 OH 6 2

N

8

N H

H H

N

OH

12

35

N 34 31

O

908 Ircinal A Type: Manzamines. C26H38N2O2 Colorless solid, mp 70 °C, [α]D25 = +48° (c = 2.9, CHCl3). Source: Sponges Haliclona sp., Amphimedon sp. and Ircinia sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 1.4 μg/mL; KB, IC50 = 4.5–4.8 μg/mL). Ref: R. Sakai, et al, JACS, 1986, 108, 6404│ K. Kondo, et al, JOC, 1992, 57, 2480│ M. Tsuda, et al, Tetrahedron, 1994, 50, 7957│ K. A. El Sayed, et al, JACS, 2001, 123, 1804 O

H H

OH

N N H

318

3 Pyrrole Indole and Imidazole Alkaloids

909 Ircinal B Type: Manzamines. C26H40N2O2 Colorless solid, mp 95 °C, [α]D25 = +18° (c = 1.1, CHCl3). Source: Sponge Ircinia sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 1.9 μg/mL; KB, IC50 = 3.5 μg/mL). Ref: K. Kondo, et al, JOC, 1992, 57, 2480 O H OH

N

HN

910 Ircinol A Type: Manzamines. C26H40N2O2 Colorless amorph. solid, mp 83–85 °C, [α]D18 = −19° (c = 0.54, MeOH). Source: Sponges Haliclona sp., Amphimedon sp. and Ircinia sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 2.4 μg/mL, KB, IC50 = 6.1 μg/mL); endothelin converting enzyme inhibitor (IC50 = 55 μg/mL). Ref: R. Sakai, et al, JACS, 1986, 108, 6404│ K. Kondo, et al, JOC, 1992, 57, 2480│ M. Tsuda, et al, Tetrahedron, 1994, 50, 7957 OH H OH

N N H

911 Kauluamine Type: Manzamines. C72H94N8O3 Unstable pale yellow solid, [α]D = +0.7° (c = 0.18, CHCl3). Source: Sponge Prianos sp. (Indonesia). Pharm: Immunosuppressant (MLR, IC50 = 1.57 μg/mL, LCV, IC50 > 25.0 μg/mL). Ref: I. Ohtani, et al, JACS, 1995, 117, 10743

3.8 Manzamines

HN H

N H N H

N H OH H

N

OH

HN

H

O

H

H

N

319

HN

912 neo-Kauluamine Type: Manzamines. C72H88N8O6 Needles (EtOH), mp 184 °C, [α]D25 = +94.6° (c = 0.1, CHCl3). Source: An unidentified sponge (order Haplosclerida, family Petrosiidae, Indo-Pacific, yield = 0.0048% dw). Pharm: Antimalarial (Plasmodium berghei, in vivo, ip dose 100 μmol/kg, potent and no apparent toxicity); cytotoxic (hmn lung and colon carcinoma, IC50 = 1.0 μg/mL). Ref: K. A. El Sayed, et al, JACS, 2001, 123, 1804

N

N H

H

OH

N HO

O

N

O N

N

H

OH

OH H N

H N

913 Keramamine B Manzamine F Type: Manzamines. C36H44N4O3 Cryst. (MeCN), mp 200 °C (dec), [α]D = +59.9° (c = 1.67, CHCl3). Source: Sponges Xestospongia sp., Petrosia sp., Acanthostrongylophora sp. (Indonesia) and family Petrosiidae sponge (Sulawesi, Indonesia). Pharm: Cytotoxic; antituberculosis (Mycobacterium tuberculosis H37Rv, MIC = 0.4–5.2 μg/mL); antimalarial (Plasmodium berghei, in vivo, ip, dose 100μmol/kg, potent and no apparent toxicity). Ref: H. Nakamura, et al, Tet. Lett.,

320

3 Pyrrole Indole and Imidazole Alkaloids

1987, 28, 621│ K. A. El Sayed, et al, JACS, 2001, 123, 1804│ K .V. Rao, JNP, 2006, 69, 1034

6

N

2

8

N H

H N

OH

OH

12 35

N 34 31

O

914 Maeganedin A Type: Manzamines. C37H52N4O2 Amorph. solid, [α]D25 = +47° (c = 0.40, MeOH). Source: Sponge Amphimedon sp. (Japan waters). Pharm: Cytotoxic (L1210, IC50 = 4.4 μg/mL); antibacterial (Sarcina lutea, Bacillus subtilis, Corynebacterium xerosis). Ref: M. Tsuda, et al, Tet. Lett., 1998, 39, 1207

H N

H H

N H OH

N

N

OH

915 Manadomanzamine A Type: Manzamines. C39H54N4O2 Powder, [α]D = −19° (c = 0.11, MeOH). Source: Sponge Acanthostrongylophora sp. (Indonesia). Pharm: Antituberculosis (Mycobacterium tuberculosis, strong); Anti-HIV-1 (strong); antifungal; cytotoxic; antimalarial (weak). Ref: J. Peng, et al, JACS, 2003, 125, 13382

22

N

H N H

H

O

N

H

HN

OH

3.8 Manzamines

321

916 Manadomanzamine B Type: Manzamines. C39H54N4O2 Powder, [α]D = −18° (c = 0.11, MeOH). Source: Sponge Acanthostrongylophora sp. (Indonesia). Pharm: Antituberculosis (Mycobacterium tuberculosis, strong); Anti-HIV-1 (strong); antifungal; cytotoxic; antimalarial (weak). Ref: J. Peng, et al, JACS, 2003, 125, 13382

22

N

H N H

H

O

N

H

OH

HN

917 Manzamine A Type: Manzamines. C36H44N4O Cryst. (MeOH) (hydrochloride), mp 240 °C (dec) (hydrochloride), [α]D25 = +50° (c = 0.28, CHCl3) (hydrochloride). Source: Sponges Haliclona sp. (Okinawa), Xestospongia sp., Pellina sp., Petrosia sp. (Indonesia, 1996), Amphimedon sp., Ircinia sp. (Okinawa), Acanthostrongylophora aff. ingens, an unidentified sponge (order Haplosclerida family Petrosiidae, Indo-Pacific, yield = 0.66% dw) and Acanthostrongylophora ingens. Pharm: Anti-inflammatory (modulation of LPS-activated brain microglia in vitro, IC50 (apparent) = 0.25 μmol/L, MMOA: TXB2 inhibition); anti-toxoplasma (in vitro, Toxoplasma gondii, 0.1 μmol/L, InRt = 70% without host cell toxicity); antiplasmodial (Plasmodium falciparum, strong); antileishmanial (Leishmania donovani, MIC = 6.25 μg/mL); antituberculosis (Mycobacterium tuberculosis, MIC = 0.4–5.2 μg/mL); cytotoxic (interesting and valuable cancer cell growth inhibitor: P388, GI50 = 0.0067 μg/mL; NCI-H460, GI50 = 0.36 μg/mL; KM20L2, GI50 = 0.37 μg/mL; DU145, GI50 = 0.60 μg/mL; BXPC3, GI50 = 0.35 μg/mL; MCF7, GI50 = 0.41 μg/mL; SF268, GI50 = 0.42 μg/mL) (Pettit, 2008); cytotoxic (Vero, IC50 = 1.7 μg/mL); cytotoxic (P388, IC50 = 0.07 μg/mL; KB, weak); cytotoxic (HeLa, IC50 = 13 μmol/L) (Furusato, 2014); insecticide; antibacterial (gram-positive and gram-negative bacteria); ATP binding in GSK-3β kinase inhibitor (specific non-competitive, IC50 = 10.2 μmol/L); proteasome inhibitor (IC50 = 2.0 μmol/L) (Furusato, 2014); inhibitor of accumulation of cholesterol ester (in macrophages, 20 μmol/L, InRt = 80%) (Furusato, 2014). Ref: R. Sakai, et al, JACS, 1986, 108, 6404│ H. Nakamura, et al, Tet. Lett., 1987, 28, 621│ K. Kondo, et al, JOC, 1992, 57, 2480│ M. Tsuda, et al, Tetrahedron, 1994, 50, 7957│ J. D. Winkler et al, JACS, 1998, 120, 6425│ K. A. El Sayed, et al, JACS, 2001, 123, 1804│ K .V. Rao, JNP, 2006, 69, 1034│ M. Hamann,et al, JNP, 2007, 70, 1397│ K. A. El Sayed, et al, JNP, 2008, 71, 300│ G. R. Pettit, et al, JNP, 2008, 71, 438│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev)│ A. Furusato, et al, Org. Lett.,2014, 16, 3888

322

3 Pyrrole Indole and Imidazole Alkaloids

6 2

N

8

N H

H

OH

12

N 35

N

H 34 31

918 Manzamine A N-oxide Type: Manzamines. C36H44N4O2 Yellow crystalline powder, [α]D = +18.6° (c = 0.35, CHCl3). Source: Sponge Xestospongia ashmorica (Philippines). Pharm: Cytotoxic (L5178, ED50 = 1.6 μg/mL); antibacterial. Ref: R. A. Edrada, et al, JNP, 1996, 59, 1056 +

–

N O

N H H

OH

N N H

919 Manzamine B Type: Manzamines. C36H46N4O Source: Sponges Acanthostrongylophora sp. (Indonesia) and Acanthostrongylophora ingens. Pharm: Antituberculosis (Mycobacterium tuberculosis, MIC = 0.4–5.2 μg/mL). Ref: K .V. Rao, JNP, 2006, 69, 1034│ A. Furusato, et al, Org. Lett.,2014, 16, 3888

6 2

N

8

N H H

H H

N

12

O

35

HN 34 31

920 Manzamine D Type: Manzamines. C36H48N4O [α]D24 = +44°. Source: Sponges Haliclona sp., Amphimedon sp. and Ircinia sp. (Okinawa). Pharm: Antituberculosis (Mycobacterium

3.8 Manzamines

323

tuberculosis H37Rv, strong). Ref: R. Sakai, et al, JACS, 1986, 108, 6404│ K. Kondo, et al, JOC, 1992, 57, 2480│ M. Tsuda, et al, Tetrahedron, 1994, 50, 7957; 1996, 52, 2319

NH

N H H

H OH

N N H

921 Manzamine E Type: Manzamines. C36H44N4O2 Cryst. (MeCN), mp 174–176 °C, [α]D = +63.7° (c = 2.51, CHCl3). Source: An unidentified sponge (order Haplosclerida, family Petrosiidae, IndoPacific, yield = 0.003% dw), sponges Xestospongia sp. and Acanthostrongylophora sp. (Indonesia). Pharm: Antileishmanial (Leishmania donovani); antituberculosis (Mycobacterium tuberculosis H37Rv, MIC < 12.5 μg/mL, InRt = 98–99%, strong). Ref: T. Ichiba, et al, Tet. Lett., 1988, 29, 3083│ K. A. El Sayed, et al, JACS, 2001, 123, 1804│ K .V. Rao, JNP, 2006, 69, 1034

N

N H

H

OH

N H

N

O

922 ent-Manzamine F Type: Manzamines. C36H44N4O3 Yellowish powder (EtOH), mp 194 °C (dec), [α]D = −44.6° (c = 0.11, CHCl3). Source: An unidentified sponge (order Haplosclerida, family Petrosiidae, Indo-Pacific, yield = 0.055% dw). Pharm: Anti-toxoplasma (in vitro, Toxoplasma gondii, 10 μmol/L, InRt = 37% without host cell toxicity); antimalarial (in vivo, strong); antituberculosis (Mycobacterium tuberculosis H37Rv, MIC < 12.5 μg/mL, InRt = 98–99%, strong). Ref: K. A. El Sayed, et al, JACS, 2001, 123, 1804

324

3 Pyrrole Indole and Imidazole Alkaloids

N

N H

H

OH

OH

N

H

N

O

923 Manzamine H Type: Manzamines. C36H50N4O Colorless solid, mp 145 °C, [α]D25 = +17° (c = 1.1, CHCl3); [α]D24 = +21°. Source: Sponges Ircinia sp. and Amphimedon sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 1.3 μg/mL; KB, IC50 = 4.6 μg/mL). Ref: K. Kondo, et al, JOC, 1992, 57, 2480│ M. Tsuda, et al, Tetrahedron, 1996, 52, 2319

NH

N H H

H OH

N HN

924 Manzamine J Type: Manzamines. C36H46N4O mp 140 °C, [α]D25 = +47° (c = 2.0, CHCl3). Source: An unidentified sponge (order Haplosclerida, family Petrosiidae, Indo-Pacific, yield = 0.0017% dw), sponge Ircinia sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 2.6 μg/mL; KB, IC50 > 10 μg/mL). Ref: K. Kondo, et al, JOC, 1992, 57, 2480│ K. A. El Sayed, et al, JACS, 2001, 123, 1804

N

N H H

N

H

HN

OH

3.8 Manzamines

325

925 Manzamine L Type: Manzamines. C36H50N4O Amorph. solid, mp 143 °C, [α]D24 = 15° (c = 0.42, CHCl3). Source: Sponge Amphimedon sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 3.7 μg/mL, KB, IC50 = 11.8 μg/mL); antibacterial (Sarcina lutea, MIC = 10 μg/mL, Staphylococcus aureus, MIC = 10 μg/mL, Bacillus subtilis, MIC = 10 μg/mL, Mycobacterium sp., MIC = 5 μg/mL). Ref: M. Tsuda, et al, Tetrahedron, 1996, 52, 319

NH

N H H

H OH

N HN

926 Manzamine X Type: Manzamines. C36H44N4O3 Yellow prisms (hexane/Me2CO), mp 250 °C, [α]D19 = +66.1° (c = 1.93, CHCl3). Source: Sponge Xestospongia sp. (Japan waters). Pharm: Cytotoxic (KB, 1C50 = 7.9 μg/mL). Ref: M. Kobayashi, et al, Tetrahedron, 1995, 51, 3727 OH N

N H

H

OH

N

N O

927 Nakadomarin A Type: Manzamines. C26H36N2O Amorph. solid, [α]D25 = −16° (c = 0.12, MeOH). Source: Sponge Amphimedon sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 1.3 μg/mL); antifungal (Trichophyton mentagrophytes, MIC = 23 μg/mL); antibacterial (gram-positive bacterium Corynebacterium xerosis, MIC = 11 μg/mL); cyclin dependent kinase 4 inhibitor (IC50 = 9.9 μg/mL). Ref: J. Kobayashi, et al, JOC, 1997, 62, 9236

326

3 Pyrrole Indole and Imidazole Alkaloids

H O N N H

928 12,28-Oxa-8-hydroxymanzamine A Type: Manzamines. C37H44N4O2 Source: Sponge Acanthostrongylophora sp. Pharm: Antifungal, Trichophyton mentagrophytes; Antibacterial, gram-positive bacterium Corynebacterium xerosis. Ref: M. Yousaf, et al, JMC, 2004, 47, 3512│ K. V. Rao, et al, JNP, 2004, 67, 1314│ K. V. Rao, et al, JNP, 2006, 69, 1034

N

OH

N H

H N

O N

929 12,34-Oxa-6-hydroxymanzamine E Type: Manzamines. C36H42N4O3 Source: Sponge Acanthostrongylophora sp. (Indonesia). Pharm: Antituberculosis (Mycobacterium tuberculosis, MIC = 0.4–5.2 μg/mL). Ref: M. Yousaf, et al, JMC, 2004, 47, 3512│ K. V. Rao, et al, JNP, 2004, 67, 1314│ K. V. Rao, et al, JNP, 2006, 69, 1034 OH 6

N

2

8

N H

H H

N

12

35

N 34 31

O

O

3.8 Manzamines

327

930 12,28-Oxamanzamine E Type: Manzamines. C36H42N4O2 Source: Sponge Acanthostrongylophora sp. (Indonesia). Pharm: Antituberculosis (Mycobacterium tuberculosis, MIC = 0.4–5.2 μg/mL). Ref: M. Yousaf, et al, JMC, 2004, 47, 3512│ K. V. Rao, et al, JNP,2004, 67, 1314│ K. V. Rao, et al, JNP, 2006, 69, 1034

6

N

2

8

N H

H H

N

12

O 35

N 34 31

O

931 Pre-neo-kauluamine Type: Manzamines. C36H45N4O31+ Source: Sponge Acanthostrongylophora ingens (Indonesia). Pharm: Proteasome inhibitor. Ref: A. H. El-Desoky, et al, JNP, 2014, 77, 1536

N

N H

H

OH

N +

N H O HO

932 1,2,3,4-Tetrahydro-2-N-methyl-8-hydroxymanzamine A Type: Manzamines. C37H50N4O2 Source: Sponges Petrosia contignata (Papua New Guinea) and Cribrochalina sp. (Papua New Guinea). Pharm: Cytotoxic (P388, ED50 = 0.8 μg/mL). Ref: P. Crews, et al, Tetrahedron, 1994, 50, 13567

328

3 Pyrrole Indole and Imidazole Alkaloids

N

OH

N H

H

OH

N N

H

933 1,2,3,4-Tetrahydro-8-hydroxymanzamine A Type: Manzamines. C36H48N4O2 Source: Sponge Petrosia contignata (Papua New Guinea). Pharm: Antituberculosis (Mycobacterium tuberculosis H37Rv). Ref: P. Crews, et al, Tetrahedron, 1994, 50, 13567

HN

OH

N H

H

OH

N N

934 1β,2,3,4-Tetrahydromanzamine B Type: Manzamines. C36H50N4O Amorph. solid, [α]D25 = −16° (c = 0.14, MeOH). Source: Sponge Amphimedon sp. (Japan waters). Pharm: Antituberculosis (Mycobacterium tuberculosis H37Rv). Ref: M. Tsuda, et al, Heterocycles, 1999, 50, 485

H N H H N

NH H

H

HN

O

3.8 Manzamines

329

935 Xestocyclamine A Type: Manzamines. C26H40N2O [α]D = −13.5° (c = 0.019, MeOH). Source: Sponge Xestospongia sp. (waters off Papua New Guinea coast). Pharm: PKC Inhibitor (IC50 = 4 μg/mL). Ref: J. Rodriguez, et al, J. Am. Chem. Soc. 1993, 115, 10436│ J. Rodriguez, et al, Tetrahedron, Lett., 1994, 35, 4719│ D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) N OH N

936 Zamamidine A Type: Manzamines. C49H60N6O Pale yellow solid, [α]D21 = −74° (c = 1, CHCl3). Source: Sponge Amphimedon sp. SS-975 (Seragaki, Okinawa). Pharm: Cytotoxic (P388, IC50 = 13.8 μg/mL, KB, inactive); antitrypanosomal (Trypanosoma brucei brucei); antiplasmodial (Plasmodium falciparum). Ref: Y. Takahashi, et al, Org. Lett., 2009, 11, 21│ M. Yamada, et al, Tetrahedron, 2009, 65, 2313; 6263 (corrigendum)

HN N H H

N H

N OH

N HN

937 Zamamidine B Type: Manzamines. C49H60N6O Pale yellow solid, [α]D21 = +51° (c = 0.4, CHCl3). Source: Sponge Amphimedon sp. SS-975 (Seragaki, Okinawa). Pharm: Cytotoxic (P388, IC50 = 14.8 μg/mL). Ref: Y. Takahashi, et al, Org. Lett., 2009, 11, 21│ M. Yamada, et al, Tetrahedron, 2009, 65, 2313; 6263 (corrigendum)

330

3 Pyrrole Indole and Imidazole Alkaloids

HN N

N H H

H

N

N O

H

HN

938 Zamamidine C Type: Manzamines. C49H58N6O Pale yellow solid, [α]D22 = −54.9° (c = 1, CHCl3). Source: Sponge Amphimedon sp. (Seragaki, Okinawa). Pharm: Cytotoxic (P388, L1210 and KB); antitrypanosomal (Trypanosoma brucei brucei); antiplasmodial (Plasmodium falciparum). Ref: Y. Takahashi, et al, Org. Lett., 2009, 11, 21│ M. Yamada, et al, Tetrahedron, 2009, 65, 2313; 6263 (corrigendum)

HN N

N H H

H

N OH

N H

N

939 Zamamiphidin A Type: Manzamines. C27H41N21+ Source: Sponge Amphimedon sp. (Zamami, Okinawa). Pharm: Antibacterial (Staphylococcus aureus, moderate). Ref: T. Kubota, et al, Org. Lett., 2013, 15, 610 H N H

+

H H N H

3.9 Tryptamine Alkaloids

331

3.9 Tryptamine Alkaloids 940 Alternatamide A N1-Methylalternatamide B Type: Tryptamine alkaloids. C18H24Br3N3O Amorph. powder. Source: Bryozoan Amathia alternata (North Carolina). Pharm: Antibacterial (Staphylococcus epidermidis, Staphylococcus haemolyticus, Bacillus subtilis, Enterococcus faecelis, Enterococcus faecium, Streptococcus pyogenes, MIC = 4– 32 μg/mL). Ref: N. -K. Lee, et al, JNP, 1997, 60, 697 O N H

Br 2 6

N

Br

H N

Br

1

941 Alternatamide B Type: Tryptamine alkaloids. C17H22Br3N3O Amorph. powder. Source: Bryozoan Amathia alternata (North Carolina). Pharm: Antibacterial (Staphylococcus epidermidis, Staphylococcus haemolyticus, Bacillus subtilis, Enterococcus faecelis, Enterococcus faecium, Streptococcus pyogenes, MIC = 4–32 μg/mL). Ref: N. -K. Lee, et al, JNP, 1997, 60, 697 O N H

Br

H N

Br N H

Br

942 Alternatamide C Type: Tryptamine alkaloids. C17H23Br2N3O Amorph. powder. Source: Bryozoan Amathia alternata (North Carolina). Pharm: Antibacterial (Staphylococcus epidermidis, Staphylococcus haemolyticus, Bacillus subtilis, Enterococcus faecelis, Enterococcus faecium, Streptococcus pyogenes, MIC = 4–32 μg/mL). Ref: N. -K. Lee, et al, JNP, 1997, 60, 697 O N H

Br

Br

6

N H

H N

332

3 Pyrrole Indole and Imidazole Alkaloids

943 Alternatamide D Type: Tryptamine alkaloids. C17H23Br2N3O Amorph. powder. Source: Bryozoan Amathia alternata (North Carolina). Pharm: Antibiotic. Ref: N. -K. Lee, et al, JNP, 1997, 60, 697 O N H

Br

H N

2

Br

N H

944 Bromochelonin B Type: Tryptamine alkaloids. C19H20Br2N2O2 Gum, [α]D = +3.7° (c = 0.27, DMSO). Source: Sponges Chelonaplysilla sp. and Dendrilla sp. Pharm: Antibacterial. Ref: S. C. Bobzin, et al, JOC, 1991, 56, 4403│ N. J. Lawrence, et al, Tet. Lett., 2001, 42, 7671 H N Br

HO O

N H

Br

945 (−)-5-Bromo-N,N-dimethyltryptophan Type: Tryptamine alkaloids. C13H15BrN2O2 Source: Sponges Thorectandra sp. (NCI, Developmental Therapeutics Program) and Smenospongia sp. (Uni. of California, Santa Cruz). Pharm: Antibacterial (Staphylococcus epidermidis, weak). Ref: N. L. Segraves, et al, JNP, 2005, 68, 1484

N OH

Br O N H

946 6-Bromo-1′-hydroxy-1′,8-dihydroaplysinopsin Type: Tryptamine alkaloids. C14H15BrN4O2 Red solid, [α]D25 = +1° (c = 0.5, MeOH). Source: Sponges Thorectandra sp. (NCI, Developmental Therapeutics Program) and Smenospongia sp. (Uni. of California, Santa Cruz). Pharm: Antibacterial (Staphylococcus epidermidis, weak). Ref: N. L. Segraves, et al, JNP, 2005, 68, 1484

3.9 Tryptamine Alkaloids

333

NH HO

N N O

Br

N H

947 (+)-5-Bromohypaphorine Type: Tryptamine alkaloids. C14H17BrN2O2 Yellow solid, [α]D25 = +46.3° (c = 0.5, MeOH). Source: Sponges Thorectandra sp. (NCI, Developmental Therapeutics Program) and Smenospongia sp. (Uni. of California, Santa Cruz). Pharm: Antibacterial (Staphylococcus epidermidis, weak). Ref: N. L. Segraves, et al, JNP, 2005, 68, 1484

N

+

–

O

Br O N H

948 6-Bromo-1′-methoxy-1′,8-dihydroaplysinopsin Type: Tryptamine alkaloids. C15H17BrN4O2 Red solid, [α]D25 = +3° (c = 1.4, MeOH). Source: Sponges Thorectandra sp. (NCI, Developmental Therapeutics Program) and Smenospongia sp. (Uni. of California, Santa Cruz). Pharm: Antibacterial (Staphylococcus epidermidis, weak). Ref: N. L. Segraves, et al, JNP, 2005, 68, 1484 NH O

N N O

Br

N H

949 6-Bromo-Nb-methyl-Na-prenyltryptamine Type: Tryptamine alkaloids. C16H21BrN2 Yellow oil. Source: Bryozoan Flustra foliacea (psychrophilic, cold water, Steingrund, Germany North Sea coast). Pharm: Affinity for neuronal nicotinic acetylcholine receptors (radioligand binding assay). Ref: L. Peters, et al, PM, 2004, 70, 883│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) H N

Br

N

334

3 Pyrrole Indole and Imidazole Alkaloids

950 Chelonin B Type: Tryptamine alkaloids. C19H21BrN2O2 Solid, mp 260 °C (dec). Source: Sponge Chelonaplysilla sp. Pharm: Antibacterial. Ref: S. C. Bobzin, et al, JOC, 1991, 56, 4403│ N. J. Lawrence, et al, Tet. Lett., 2001, 42, 7671 H N HO O

N H

Br

951 Clionamide Type: Tryptamine alkaloids. C19H18BrN3O4 Yellow powder, sensitive to light and to air, [α]D = +32.1° (c = 2.12, MeOH). Source: Sponge Cliona celata (burrowing sponge). Pharm: Antimicrobial. Ref: R. J. Andersen, et al, Can. J. Chem., 1979, 57, 2325 H

O

N H

Br

OH NH2

OH

N H

OH

952 Conicamine Type: Tryptamine alkaloids. C13H17N21+ Source: Ascidian Aplidium conicum. Pharm: Histamine antagonist. Ref: A. Aiello, et al, BoMCL, 2003, 13, 4481

N

+

N H

953 Deformylflustrabromine Type: Tryptamine alkaloids. C16H21BrN2 Yellow oil. Source: Bryozoan Flustra foliacea (psychrophilic, cold water, Steingrund, Germany North Sea coast). Pharm: Antibacterial (Escherichia coli and Staphylococcus aureus, inhibits biofilm formation); affinity to nicotinic acetylcholine (nACh) receptors (high and subtype selective). Ref: L. Peters, et al, JNP, 2002, 65, 1633│ L. Peters, et al, Planta. Med., 2004, 70, 883│ F. Sala, et al, Neurosci. Lett., 2005, 373, 144│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)│ C. A. Bunders, et al, JACS, 2011, 133, 20160

3.9 Tryptamine Alkaloids

335

H N

Br

N H

954 Deformylflustrabromine B Type: Tryptamine alkaloids. C16H21BrN2 Source: Bryozoan Flustra foliacea. Pharm: Affinity to nicotinic acetylcholine (nACh) receptors (high and subtype selective). Ref: L. Peters, et al, JNP, 2002, 65, 1633│ L. Peters, et al, Planta. Med., 2004, 70, 883│ F. Sala, et al, Neurosci. Lett., 2005, 373, 144 H N

Br

N

955 5,6-Dibromo-L-hypaphorine Type: Tryptamine alkaloids. C14H16Br2N2O2 Pale yellow oil, [α]D20 = +28° (c = 0.06, MeOH-1N HCl 8:2). Source: Sponge Hyrtios sp. (near Kia I., Fiji). Pharm: PLA2 inhibitor (bee venom PLA2, IC50 = (0.20 ± 0.01)mmol/L); antioxidant (Oxygen Radical Absorbance Capacity (ORAC) = (0.22 ± 0.04), significant). Ref: A. Longeon, et al, Mar. Drugs, 2011, 9, 879 O Br

–

O +

Br

N H

N

956 5,6-Dibromotryptamine Type: Tryptamine alkaloids. C10H10Br2N2 mp 110–120 °C. Source: Sponges Hyrtios sp. and Polyfibrospongia maynardii (Caribbean Sea). Pharm: PLA2 inhibitor (bee venom PLA2, IC50 = (0.62 ± 0.01)mmol/L); antibacterial (in vitro but not in vivo, gram-negative and gram-positive bacteria). Ref: A. Longeon, et al, Mar. Drugs, 2011, 9, 879│ G. E. Van Lear, et al, Tet. Lett., 1973, 4, 299 Br Br

N H

NH2

336

3 Pyrrole Indole and Imidazole Alkaloids

957 N,N-Dimethyl-5-bromotryptamine Type: Tryptamine alkaloids. C12H15BrN2 Cryst. (MeOH aq), mp 98–99 °C, mp 90–92 °C. Source: Sponges Smenospongia aurea and Polyfibrospongia echina, ascidian Eudistoma fragum (New Caledonia). Pharm: Antimicrobial. Ref: P. Djura, et al, JOC, 1980, 45, 1435│ A. A. Tymiak, et al, Tetrahedron, 1985, 41, 1039│ C. Debitus, et al, JNP, 1988, 51, 799 N

Br N H

958 N,N-Dimethyl-5,6-dibromotryptamine Type: Tryptamine alkaloids. C12H14Br2N2 Cryst. (MeOH aq), mp 113–115 °C. Source: Sponges Hyrtios sp., Smenospongia echina, Smenospongia aurea and Verongula gigantea. Pharm: PLA2 inhibitor (bee venom PLA2, IC50 = (0.77 ± 0.05)mmol/L); antioxidant (Oxygen Radical Absorbance Capacity (ORAC) = (0.06 ± 0.01), significant); antimicrobial. Ref: A. Longeon, et al, Mar. Drugs, 2011, 9, 879│ P. Djura, et al, JOC, 1980, 45, 1435 Br Br

N H

N

959 (±)-Gelliusine A Type: Tryptamine alkaloids. C30H30Br2N6O Source: Sponges Gellius sp. and Orina sp. (deep water, New Caledonia). Pharm: Serotonin receptor agonist (10–100 μmol/L); receptor binding activity (5 μg/mL, somatostatin receptor site, totally displaced radioactive ligand); receptor binding activity (neuropeptide Y receptor site, 5 μg/mL, 90% inhibition of ligand binding); receptor binding activity (hmn B2 bradykinin receptor site, 5 μg/mL, 100% inhibition of ligand binding); AMPA-binding assay (quisqualate site of glutamate receptor); calcitonin gene related protein (CGRP)-binding assay; galanin-binding assay with a hmn cell line (BOWES); glycine-binding assay (regulatory site of NMDA receptor, Gly); neurotensin-binding assay (NT) and vasointestinal polypeptide-binding assay (VIP). Ref: G. Bifulco, et al, JNP, 1994, 57, 1294

3.9 Tryptamine Alkaloids

337

NH2 NH2

HO NH2

8''

N H

8

Br N H

N H

Br

960 (±)-Gelliusine B Type: Tryptamine alkaloids. C30H30Br2N6O Source: Sponges Gellius sp. and Orina sp. (deep water, New Caledonia). Pharm: Receptor binding activity (5 μg/mL, somatostatin receptor site, totally displaced radioactive ligand); receptor binding activity (neuropeptide Y receptor site, 5 μg/mL, 62% inhibition of ligand binding); receptor binding activity (hmn B2 bradykinin receptor site, 5 μg/mL, 93% inhibition of ligand binding); AMPA-binding assay (quisqualate site of glutamate receptor); calcitonin gene related protein (CGRP)-binding assay; galanin-binding assay with a hmn cell line (BOWES); glycine-binding assay (regulatory site of NMDA receptor, Gly); neurotensin-binding assay (NT) and vasointestinal polypeptide-binding assay (VIP). Ref: G. Bifulco, et al, JNP, 1994, 57, 1294 NH2 NH2

HO NH2

8''

N H

8

Br N H

N H

Br

diastereoisomer of Gelliusine A

961 (±)-Gelliusine C Type: Tryptamine alkaloids. C30H30Br2N6O Source: Sponge Orina sp. (New Caledonia). Pharm: Antiserotonin (8–50 μmol/L). Ref: G. Bifulco, et al, JNP, 1995, 58, 1254 H N

NH2

NH2

Br NH2

HO N H

Br N H

338

3 Pyrrole Indole and Imidazole Alkaloids

962 (±)-Gelliusine D Type: Tryptamine alkaloids. C20H21BrN4O Source: Sponge Orina sp. (New Caledonia). Pharm: Antiserotonin (8–50 μmol/L). Ref: G. Bifulco, et al, JNP, 1995, 58, 1254 H N

NH2

NH2

Br HO N H

963 (±)-Gelliusine E Type: Tryptamine alkaloids. C20H21BrN4O Source: Sponge Orina sp. (New Caledonia). Pharm: Antiserotonin (8–50 μmol/L); receptor binding activity (5 μg/mL, somatostatin receptor site, displaced radioactive ligand 87%); receptor binding activity (neuropeptide Y receptor site, 5 μg/mL, 63% inhibition of ligand binding); receptor binding activity (hmn B2 bradykinin receptor site, 5 μg/mL, 63% inhibition of ligand binding); AMPA-binding assay (quisqualate site of glutamate receptor); calcitonin gene related protein (CGRP)-binding assay; galanin-binding assay with a hmn cell line (BOWES); glycine-binding assay (regulatory site of NMDA receptor, Gly); neurotensin-binding assay (NT) and vasointestinal polypeptide-binding assay (VIP). Ref: G. Bifulco, et al, JNP, 1995, 58, 1254 NH2 NH2

HO N H

Br N H

964 (±)-Gelliusine F Type: Tryptamine alkaloids. C20H20Br2N4 Source: Sponge Orina sp. (New Caledonia). Pharm: Antiserotonin (8–50 μmol/L); receptor binding activity (5 μg/mL, somatostatin receptor site, displaced radioactive ligand 91%); receptor binding activity (neuropeptide Y receptor site, 5 μg/mL, 67% inhibition of ligand binding); receptor binding activity (hmn B2 bradykinin receptor site, 5 μg/mL, 89% inhibition of ligand binding); AMPA-binding assay (quisqualate site of glutamate receptor); calcitonin gene related protein (CGRP)-binding assay; galanin-binding assay with a hmn cell line (BOWES); glycine-binding assay (regulatory site of NMDA receptor, Gly); neurotensin-binding assay (NT) and vasointestinal polypeptide-binding assay (VIP). Ref: G. Bifulco, et al, JNP, 1995, 58, 1254

3.9 Tryptamine Alkaloids

339

NH2 NH2 N H

Br

Br N H

965 Hermitamide B Type: Tryptamine alkaloids. C25H38N2O2 Pale yellow oil, [α]D26 = −4.5° (c = 0.10, CHCl3). Source: Cyanobacterium Lyngbya majuscula (Papua New Guinea). Pharm: Cytotoxic (neuro-2a cells in tissue culture, IC50 = 5.5 μg/mL); anticancer-Cell-Effect (model: HEK, mechanism: voltage-gated Na channel inhibition); LD50 (brine shrimp Artemia salina bioassay) = 18 μmol/L; ichthyotoxic (goldfish, LD50 = 25 μmol/L). Ref: T. Tan, et al, JNP, 2000, 63, 952│ E. O. De Oliveira, et al, BoMC 2011, 19, 4322

H N

7S

O

N H

O

966 (1H-indol-3-yl) oxoacetamide Type: Tryptamine alkaloids. C10H6Br2N2O2 Source: Sponges Spongosorites sp. (off the coast of Jeju I., Korea) and Rhopaloeides odorabile. Pharm: PLA2 inhibitor (bee venom PLA2, IC50 = (1.17 ± 0.05)mmol/L). Ref: A. Longeon, et al, Mar. Drugs, 2011, 9, 879│ B. Bao, et al, Mar. Drugs, 2007, 5, 31 O

NH2

Br Br

O

N H

967 JBIR 81 Type: Tryptamine alkaloids. C24H34N4O3 Source: Marine-derived fungus Aspergillus sp. from brown alga Sargassum sp. (Ishigaki I. Okinawa). Pharm: Antioxidant (free radical scavenger, to protect N18-RE-105 cells against L-glutamate toxicity, considerably more potent than control α-Tocopherol). Ref: T. Kagamizono, et al, Tet. Lett., 1997, 38, 1223│ M. Izumikawa, et al, J. Antibiot., 2010, 63, 389

340

3 Pyrrole Indole and Imidazole Alkaloids

O O

NH N

N H

O

N H

968 JBIR 82 Type: Tryptamine alkaloids. C29H42N4O3 Source: Marine-derived fungus Aspergillus sp. from brown alga Sargassum sp. (Ishigaki I. Okinawa). Pharm: Antioxidant (free radical scavenger, to protect N18-RE-105 cells against L-glutamate toxicity, considerably more potent than control α-Tocopherol). Ref: T. Kagamizono, et al, Tet. Lett., 1997, 38, 1223│ M. Izumikawa, et al, J. Antibiot., 2010, 63, 389 O O

NH N

N H

O

N H

969 Konbamidin Type: Tryptamine alkaloids. C13H14N2O4 Powder, [α]D21 = +15° (c = 0.27, MeOH). Source: Sponge Ircinia sp. (Okinawa). Pharm: Cytotoxic (HeLa). Ref: H. Shinonaga, et al, JNP, 1994, 57, 1603 COOH COOH

HN

N H

970 Kororamide A Type: Tryptamine alkaloids. C18H21Br3N3O1+ Source: Bryozoan Amathia tortuosa (northern New South Wales, Australia). Pharm: Antiplasmodial (CSPF and CRPF, marginal). Ref: A. R. Carroll, et al, Tet. Lett., 2012, 53, 2873 O N Br N

Br Br

H N

+

H

3.9 Tryptamine Alkaloids

341

971 Kottamide A Type: Tryptamine alkaloids. C21H24Br2N4O2 Amorph. solid, [α]D20 = +160° (c = 0.2, MeOH). Source: Ascidian Pycnoclavella kottae (New Zealand). Pharm: Cytotoxic (P388, IC50 = 20 μmol/L); cytotoxic (NCI’s panel average values: GI50 = 15.1 μmol/L, TGI = 33.9 μmol/L, LC50 = 67.6 μmol/L); cytotoxic/antiviral (african green monkey kidney cell line BSC-1infected with RNA virus PV1, cytotoxic zone size > 4.5 mm, 240 μg loading; some antiviral activity, zone size = 1–2 mm). Ref: D. R. Appleton, et al, JOC, 2002, 67, 5402

O 5

Br

N O

N H

N H

N H

Br

972 Kottamide B Type: Tryptamine alkaloids. C21H25BrN4O2 Amorph. solid, [α]D20 = +245° (c = 0.2, MeOH). Source: Ascidian Pycnoclavella kottae (New Zealand). Pharm: Cytotoxic (mixture with Kottamide C, P388, IC50 = 14 μmol/L). Ref: D. R. Appleton, et al, JOC, 2002, 67, 5402

O

N O

N H

5

N H

N H

Br

973 Kottamide C Type: Tryptamine alkaloids. C21H25BrN4O2 Source: Ascidian Pycnoclavella kottae (New Zealand). Pharm: Cytotoxic (mixture with Kottamide B, P388, IC50 = 14 μmol/L). Ref: D. R. Appleton, et al, JOC, 2002, 67, 5402

O Br

N H

5

N H

N O N H

974 Kottamide D Type: Tryptamine alkaloids. C19H20Br2N4O2 Amorph. solid, [α]D20 = +150° (c = 0.2, MeOH). Source: Ascidian Pycnoclavella kottae (New Zealand). Pharm: Cytotoxic (P388, IC50 = 36 μmol/L); anti-metabolic (IC50 = 6–10 μmol/L); anti-inflammatory

342

3 Pyrrole Indole and Imidazole Alkaloids

(using activated hmn peripheral blood neutrophils, 200 μmol/L, inhibits superoxide production, inhibits response to inflammation promoting agents N-formylmethionylleucylphenylalanine (fMLP) and phorbol myristate acetate (PMA), InRt = 95%– 100%). Ref: D. R. Appleton, et al, JOC, 2002, 67, 5402 O Br Br

5

N O

N H

N H

N H

975 (–)-(R)-Leptoclinidamine B Type: Tryptamine alkaloids. C16H19N5O5 [α]D20 = −20.6° (c = 0.033, MeOH) (TFA salt). Source: Ascidians Leptoclinides dubius (Lembeh Strait, North Sulawesi, Indonesia) and Herdmania momus (Jeju I., S. Korea). Pharm: Transactivats PPAR-γ (cell-based luciferase reporter assay). Ref: H. Yamazaki, et al, Mar. Drugs, 2012, 10, 349│ J. L. Li, et al, JNP, 2012, 75, 2082; 2013, 76, 815 O

HO

H N

COOH

O N H N H 2N

NH2

976 N-Methyl-5,6-dibromotryptamine Type: Tryptamine alkaloids. C11H12Br2N2 mp 132–134 °C. Source: Sponges Hyrtios sp. and Polyfibrospongia maynardii. Pharm: PLA2 inhibitor (bee venom PLA2, IC50 = (0.33 ± 0.03)mmol/L); antibacterial (in vitro not in vivo, gram-positive and -negative bacteria). Ref: A. Longeon, et al, Mar. Drugs, 2011, 9, 879│ G. E. Van Lear, et al, Tet. Lett., 1973, 4, 299 Br

Br

N H

NH

977 3-Oximido-ethyl-6-prenylindole Type: Tryptamine alkaloids. C15H18N2O Source: Marine-derived streptomycete Streptomyces sp. BL-49-58-005. Pharm: Cytotoxic (panel of 14 different tumor, for LNCaP, HMEC1, K562, PANC1, LoVo and LoVo-DOX, GI50 values within micromolar range). Ref: J. M. Sánchez López, et al, JNP, 2003, 66, 863

3.9 Tryptamine Alkaloids

343

N OH

N H

978 Plakohypaphorine B Type: Tryptamine alkaloids. C14H16I2N2O2 Yellow solid, [α]D25 = +30.4° (c = 1.2, MeOH/CF3COOH). Source: Sponge Plakortis simplex (Caribbean Sea). Pharm: Antihistaminic (significant). Ref: C. Campagnuolo, et al, EurJOC, 2003, 2003, 284│ F. Borrelli, et al, EurJOC, 2004, 2004, 3227 O

–

O N

+

N H

I I

979 Plakohypaphorine C Type: Tryptamine alkaloids. C14H16I2N2O2 Yellow solid, [α]D25 = +29.1° (c = 1, MeOH/ CF3COOH). Source: Sponge Plakortis simplex (Caribbean Sea). Pharm: Antihistaminic (significant). Ref: C. Campagnuolo, et al, EurJOC, 2003, 2003, 284│ F. Borrelli, et al, EurJOC, 2004, 2004, 3227 O

–

O N

I

+

N H I

980 Plakohypaphorine D Type: Tryptamine alkaloids. C14H16I2N2O2 Pale yellow solid, [α]D25 = +27.1° (c = 2, MeOH/TFA). Source: Sponge Plakortis simplex (Caribbean Sea). Pharm: Antihistaminic (significant). Ref: C. Campagnuolo, et al, EurJOC, 2003, 2003, 284│ F. Borrelli, et al, EurJOC, 2004, 2004, 3227

344

3 Pyrrole Indole and Imidazole Alkaloids

O

N

I I

–

O +

N H

981 Tetraacetylclionamide Type: Tryptamine alkaloids. C27H26BrN3O8 Cryst. (THF/diisopropyl ether), mp 209– 211 °C, [α]D = +45° (c = 0.7, Me2CO). Source: Sponge Cliona celata (burrowing sponge). Pharm: Antimicrobial. Ref: R. J. Andersen, Tet. Lett., 1978, 2541│ U. Schmidt, et al, Angew. Chem., Int. Ed. Engl., 1984, 23, 991│ U. Schmidt, et al, Licbigs Ann. Chem., 1985, 785 O O

Br

N H

O

O

O

NH

O

N H

O

O

982 Flustramine A Type: Cyclotryptamine alkaloids. C21H29BrN2 Liq., [α]D20 = −76.9° (c = 6.6, EtOH). Source: Bryozoan Flustra foliacea (psychrophilic, cold water, North Sea; Minas Basin, Nova Scotia). Pharm: Muscle relaxant; potassium-channel blocking activity; cytotoxic (HCT116, modest). Ref: J. S. Carlé, et al, JACS, 1979, 101, 4012│ J. S. Carlé, et al, JOC, 1980, 45, 1586; 1981, 46, 3440│ M. S. Morales-Ríos, et al, JOC, 2001, 66, 1186│ L. Peters, et al, JNP, 2002, 65, 1633│ M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)

Br

N

H

N

983 Flustramine B Type: Cyclotryptamine alkaloids. C21H29BrN2 Source: Bryozoan Flustra foliacea (psychrophilic, cold water, North Sea; Minas Basin, Nova Scotia). Pharm: Muscle relaxant. Ref: J. S. Carlé, et al, JOC, 1980, 45, 1586; 1981, 46, 3440│ M. S. Morales-Rios, JOC, 1999, 64, 1086; 2001, 66, 1186│ M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)

3.9 Tryptamine Alkaloids

Br

N

H

345

N

984 Flustramine E Type: Cyclotryptamine alkaloids. C16H21BrN2 [α]D20 = −1136° (c = 0.0088, EtOH). Source: Bryozoan Flustra foliacea (psychrophilic, cold water, Danish, North Sea). Pharm: Antifungal (Botrytis cinerea, Rhizoctonia solani). Ref: P. B. Holst, et al, JNP, 1994, 57, 997│ M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)

Br

N N H H

985 Flustramine F Type: Cyclotryptamine alkaloids. C18H23BrN2O Oil, [α]D = −22° (c = 0.2, CHCl3). Source: Bryozoan Flustra foliacea (Minas Basin, Bay of Fundy, Canada). Pharm: Antifungal (Candida utilis ATCC 9950, 1.4μmoL/disk, IZD = 18 mm). Ref: S. J. Rochfort, et al, JNP, 2009, 72, 1773

4

Br

7

8

8a 2

N

N

O

986 Flustramine I Type: Cyclotryptamine alkaloids. C16H21BrN2O Oil. [α]D = −87° (c = 0.18, CHCl3). Source: Bryozoan Flustra foliacea (Minas Basin, Bay of Fundy, Canada). Pharm: Antibacterial (1.5 μmoL/disk, Escherichia coli ATCC 11775, IZD = 25 mm, Micrococcus luteus ATCC 49732, IZD = 29 mm); antifungal (1.5 μmoL/disk, Candida utilis ATCC 9950, IZD = 29 mm, Saccharomyces cereVisiae ATCC 9763, IZD = 15 mm). Ref: S. J. Rochfort, et al, JNP, 2009, 72, 1773

346

3 Pyrrole Indole and Imidazole Alkaloids

OH 4 7

Br

8

8a 2

N H

N

987 Flustramine L Type: Cyclotryptamine alkaloids. C21H29BrN2O Oil. [α]D = −53° (c = 0.3, CHCl3). Source: Bryozoan Flustra foliacea (Minas Basin, Bay of Fundy, Canada). Pharm: Antibacterial (1.2 μmoL/disk, Escherichia coli ATCC 11775, IZD = 24 mm, Micrococcus luteus ATCC 49732, IZD = 25 mm); antifungal (1.2 μmoL/disk, Candida utilis ATCC 9950, IZD = 30 mm, Saccharomyces cereVisiae ATCC 9763, IZD = 20 mm). Ref: S. J. Rochfort, et al, JNP, 2009, 72, 1773

OH 4 7

Br

8

8a 2

N N H H

3.10 Chaetocin-like Alkaloids 988 Asperazine Type: Chaetocin-like alkaloids. C40H36N6O4 Amorph. powder, [α]D = +53° (c = 0.2, MeOH). Source: Marine-derived fungus Aspergillus niger (saltwater culture) from sponge Hyrtios proteus (Florida). Pharm: Selective cytotoxic (Corbett-Valeriote soft agar disk diffusion assay, in the primary assay, 50 μg/desk: zone sizes of L1210/C38/H116orCX1 system = 400/40/300 versus cytosine arabinoside (standard chemotherapeutic agent); 2.5 μg/desk: zone sizes = 910/610/250, which indicates excellent leukemia selectivity; in secondary assay, 50 μg/desk: L1210/CFU-GM, zone sizes = 450/50; 0.5 μg/desk: L1210/CFU-GM, zone sizes > 1000/45, so asperazineis leukemia selective). Ref: M. Varoglu, et al, JOC, 1997, 62, 7078

3.10 Chaetocin-like Alkaloids

O

347

H N

H N

HN

O

H N HN

O

NH O

989 Brevicompanine A Type: Chaetocin-like alkaloids. C22H29N3O2 Amorph. solid, mp 61–65 °C, [α]D20 = −237.5° (c = 0.7, EtOH). Source: Fungus Penicillium brevicompactum. Pharm: Plant growth regulator. Ref: K. Sprogøe, et al, Tetrahedron, 2005, 61, 8718│ M. Kusano, et al, JCS Perkin I, 1998, 2823

H

O NH

N N H

H

O

H

990 Brevicompanine B Type: Chaetocin-like alkaloids. C22H29N3O2 Amorph. solid, mp 79–82 °C, [α]D20 = −228.3° (c = 0.5, EtOH). Source: Fungi Penicillium brevicompactum and Aspergillus janus IBT 22274. Pharm: Plant growth regulator. Ref: K. Sprogøe, et al, Tetrahedron, 2005, 61, 8718│ M. Kusano, et al, JCS Perkin I, 1998, 2823

H

O NH

N N H

H

O

H

991 Brevicompanine C Type: Chaetocin-like alkaloids. C21H27N3O2 Cryst. (EtOAc), mp 94–96 °C, [α]D20 = −321.7° (c = 0.6, EtOH). Source: Fungus Penicillium brevicompactum. Pharm: Plant growth regulator. Ref: Y. Kimura, et al, JNP, 2005, 68, 237

H

O NH

N N H

H

O

H

348

3 Pyrrole Indole and Imidazole Alkaloids

992 Brevicompanine E Type: Chaetocin-like alkaloids. C25H33N3O3 Powder (MeOH), [α]D17 = −140° (c = 1.35, MeOH). Source: Marine-derived fungus Penicillium sp. from deep ocean sediment (depth of 5080 m). Pharm: Inhibits lipopolysaccharide (LPS)-induced nitric oxide production (BV2 microglial, at concentrations at which it did not exhibit cytotoxic effects). Ref: L. Du, et al, CPB, 2009, 57, 873

H

O NH 3

N

6

H

N

O

O

993 Brevicompanine H Type: Chaetocin-like alkaloids. C24H31N3O3 Powder (MeOH), [α]D17 = −142° (c = 0.5, MeOH). Source: Marine-derived fungus Penicillium sp. from deep ocean sediment (depth of 5080 m). Pharm: Inhibits lipopolysaccharide (LPS)-induced nitric oxide production (BV2 microglial, at concentrations at which it did not exhibit cytotoxic effects). Ref: L. Du, et al, CPB, 2009, 57, 873

H

O NH 3

N

6

H

N

O

O

994 Gliocladine C Type: Chaetocin-like alkaloids. C22H16N4O3 Pale yellow powder (CH2Cl2/MeOH), mp 180–183 °C, [α]D16 = +131.4° (c = 0.07, CHCl3). Source: Marine-derived fungus Gliocladium roseum OUPS-N132 from sea hare Aplysia kurodai. Pharm: Cytotoxic. Ref: Y. Usami, et al, Heterocycles, 2004, 63, 1123 H N

O

N N H H

N

O O

3.10 Chaetocin-like Alkaloids

349

995 Leptosin O Type: Chaetocin-like alkaloids. C33H36N6O7S2 Source: Marine-derived fungus Leptosphaeria sp. OUPS-N80 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388). Ref: T. Yamada, et al, Heterocycles, 2004, 63, 641 OH

O H H N N

N OH O

OH O N N H H O

N S S

996 Leptosin P Type: Chaetocin-like alkaloids. C33H36N6O7S2 Source: Marine-derived fungus Leptosphaeria sp. OUPS-N80 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388). Ref: T. Yamada, et al, Heterocycles, 2004, 63, 641 OH

O H H N N

N OH O

OH O N N H H O

N S S

997 Neoechinulin A Type: Chaetocin-like alkaloids. C19H21N3O2 Ivory cryst. (MeOH), mp 264–265 °C, [α]D23 = −54° (c = 0.1, MeOH). Source: Marine-derived fungus Penicillium griseofulvum. Pharm: Cytotoxic (interesting and valuable cancer cell growth inhibitor: P388, GI50 = 0.21 μg/mL; OVCAR-3, GI50 = 0.24 μg/mL; NCI-H460, GI50 = 0.21 μg/mL; KM20L2, GI50 = 0.19 μg/mL; DU145, GI50 = 0.27 μg/mL; BXPC3, GI50 = 0.25 μg/mL; SF295, GI50 = 0.21 μg/mL) (Pettit, 2008); antioxidant (high activity); food preservative. Ref: G. R. Pettit, et al, JNP, 2008, 71, 438

350

3 Pyrrole Indole and Imidazole Alkaloids

O NH HN N H

O

998 Neoechinulin B Type: Chaetocin-like alkaloids. C19H19N3O2 Yellow cryst. (MeOH), mp 234–236 °C. Source: Marine-derived fungus Penicillium griseofulvum, mangrove-derived fungus Aspergillus effuses H1-1 from unidentified mangrove (rhizosphere soil, Fujian Province, China), mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 70.48%, IC50 = 27.4 μmol/L, CC50 > 200 μmol/L); antivirus (LN/1109 (H1N1), IC50 = 16.89 μmol/L, HN/1222 (H3N2), IC50 = 22.22 μmol/L, high potency and broad-spectrum activities against influenza viruses with less drug resistance make Neoechinulin B as a new lead for development of potential inhibitor of influenza viruses). Ref: K. Kuramochi, et al, Synthesis, 2008, 3810│ H. Gao, et al, Arch. Pharmacal Res., 2013, 36, 952│ X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 O NH HN N H

O

999 Norcardioazine A Type: Chaetocin-like alkaloids. C29H30N4O3 Source: Marine-derived actinomycete Nocardiopsis sp. CMB-M0232 (sediment, South Molle, I., Brisbane, Australia). Pharm: Inhibitor of multidrug resistance factor P-glycoprotein; reverses doxorubicin resistance (in MDR (multi-drug resistant) SW620 Ad300 cells). Ref: R. Raju, et al, Org. Lett., 2011, 13, 2770

H

O

H

N

N N N

H

O

H O

1000 Plectosphaeroic acid A Type: Chaetocin-like alkaloids. C39H32N6O10S2 Red–orange solid, [α]D23 = +96.9° (c = 0.33, MeOH). Source: Marine-derived fungus Plectosphaerella cucumerina (sediments, British Columbia). Pharm: Indoleamine 2,3-dioxygenase (IDO) inhibitor (IDO

3.10 Chaetocin-like Alkaloids

351

is an molecular target for treating cancer involved in immune escape). Ref: G. C. Prendergast, Oncogene, 2008, 27, 3889│ G. Carr, et al, Org. Lett., 2009, 11, 2996

HN HO

O

S

6

N N

N

S

3

OH

14

H O O OH

O

OH

N

NH2

O

O

1001 Plectosphaeroic acid B Type: Chaetocin-like alkaloids. C39H32N6O9S2 Red–orange solid, [α]D23 = +69.8° (c = 0.27, MeOH). Source: Marine-derived fungus Plectosphaerella cucumerina (sediments, British Columbia). Pharm: Indoleamine 2,3-dioxygenase (IDO) inhibitor (IC50 ≈ 2 μmol/L). Ref: G. C. Prendergast, Oncogene, 2008, 27, 3889│ G. Carr, et al, Org. Lett., 2009, 11, 2996

HN HO

S

O 6

N

N 3

S 14

N

H O O OH

O

OH

N

NH2

O

O

1002 Plectosphaeroic acid C Type: Chaetocin-like alkaloids. C37H26N6O10S3 Red–orange solid, [α]D23 = +135.6° (c = 0.17, MeOH). Source: Marine-derived fungus Plectosphaerella cucumerina (sediments, British Columbia). Pharm: Indoleamine 2,3-dioxygenase (IDO) inhibitor (IC50 ≈ 2 μmol/L). Ref: G. C. Prendergast, Oncogene, 2008, 27, 3889│ G. Carr, et al, Org. Lett., 2009, 11, 2996

352

3 Pyrrole Indole and Imidazole Alkaloids

HN O

HO

N

S

6

N

S

OH

S 3

14

N H O O OH

O

OH

N

NH2

O

O

1003 Roquefortine C Type: Chaetocin-like alkaloids. C22H23N5O2 Needles +1MeOH (MeOH aq), mp 195–200 ° C (dec), mp 225–228 °C (dec), [α]D15 = −764° (c = 0.5, Py), [α]D22 = −703° (c = 1, CHCl3), Source: Marine-derived fungus Penicillium sp. (common constit. of blue cheese), terrestrial fungi (Penicillium spp.). Pharm: Neurotoxin; LD50 (mus, ipr) = 15 mg/kg. Ref: G. Bringmann, et al, Tetrahedron, 2005, 61, 7252│ L. Du, et al, Tetrahedron, 2009, 65, 1033

H

20

O

19 11a 6

N H

NH 3

N H

12

O N 16

N H

1004 Roquefortine F Type: Chaetocin-like alkaloids. C23H25N5O3 Yellow solid (MeOH), [α]D20 = −281.2° (c = 0.1, MeOH). Source: Deep-sea fungus Penicillium sp. F23-2 (sediment, depth of 5080 m). Pharm: Cytotoxic (A549, IC50 = 14.0 μmol/L; HL60, IC50 = 33.6 μmol/L; Bel7402, IC50 = 13.0 μmol/L; Molt4, IC50 = 21.2 μmol/L). Ref: L. Du, et al, Tetrahedron, 2009, 65, 1033│ L. Du, et al, J. Antibiot., 2010, 63, 165

H

20

O

19 11a 6

N

NH 3

N H

12

O N

O 16

N H

3.10 Chaetocin-like Alkaloids

353

1005 Roquefortine G Type: Chaetocin-like alkaloids. C29H35N5O4 Yellow solid (MeOH), [α]D20 = −244.1° (c = 0.09, MeOH). Source: Deep-sea fungus Penicillium sp. F23-2 (sediment, depth of 5080 m). Pharm: Cytotoxic (A549, IC50 = 42.5 μmol/L; HL60, IC50 = 36.6 μmol/L; Bel7402, IC50 > 50 μmol/L; Molt4, IC50 > 50 μmol/L). Ref: L. Du, et al, Tetrahedron, 2009, 65, 1033│ L. Du, et al, J. Antibiot., 2010, 63, 165

O

20

O

19 11a

NH 3

N

6

H

N H

12

O N N 16

O

1006 Roquefortine H Type: Chaetocin-like alkaloids. C28H33N5O3 Yellow solid (MeOH), [α]D20 = −430° (c = 0.01, MeOH). Source: Deep-sea fungus Penicillium sp. F23-2 (deep ocean sediment, unspecified location). Pharm: Cytotoxic (A549, IC50 > 100 μmol/L; HL60, IC50 > 100 μmol/L). Ref: L. Du, et al, Tetrahedron, 2009, 65, 1033│ L. Du, et al, J. Antibiot., 2010, 63, 165

H

O NH

N N H

H

O

O

N N

1007 Roquefortine I Type: Chaetocin-like alkaloids. C23H25N5O3 Yellow solid (MeOH), [α]D20 = −285° (c = 0.01, MeOH). Source: Deep-sea fungus Penicillium sp. F23-2 (deep ocean sediment, unspecified location). Pharm: Cytotoxic (A549, IC50 > 100 μmol/L; HL60, IC50 > 100 μmol/L). Ref: L. Du, et al, Tetrahedron, 2009, 65, 1033│ L. Du, et al, J. Antibiot., 2010, 63, 165

354

3 Pyrrole Indole and Imidazole Alkaloids

O

O NH

N N H

H

O N N H

3.11 Indole-Imidazole Alkaloids 1008 Aplysinopsin Type: Indole-imidazole alkaloids. C14H14N4O Fine yellow needles + 1H2O (MeOH aq + Et2NH), mp 235–237 °C (dec), mp 232–233 °C. Source: Sponges Verongia spengelii and Thorecta sp., anthozoan Astroides calycularis. Pharm: Antibiotic; antineoplastic. Ref: K. H. Hollenbeak, et al, JNP, 1977, 40, 479│ E. Fattorusso, et al, JNP, 1985, 48, 924│ D. Bialonska, et al, Mar. Drugs, 2009, 7, 166 (rev) 8

N 2' NH

1

6

N 4'

O

N H

1009 6-Bromo-1′-ethoxy-1′,8-dihydroaplysinopsin Type: Indole-imidazole alkaloids. C16H19BrN4O2 Red solid, [α]D25 = +19.3° (c = 0.05, MeOH). Source: Sponges Thorectandra sp. (NCI, Developmental Therapeutics Program) and Smenospongia sp. (Uni. of California, Santa Cruz). Pharm: Antibacterial (Staphylococcus epidermidis, weak). Ref: N. L. Segraves, et al, JNP, 2005, 68, 1484│ D. Bialonska, et al, Mar. Drugs, 2009, 7, 166 (rev) O 8 6

Br

N 2' NH

1

N H

O

N 4'

1010 Bunodosine 391 BDS 391 Type: Indole-imidazole alkaloids. C16H15BrN4O3 Source: Sea anemone Bunodosoma cangicum. Pharm: Analgetic effects mediated via serotonin receptors. Ref: A. J. Zaharenko, et al, JNP, 2011, 74, 378

3.11 Indole-Imidazole Alkaloids

H N

Br O

N H

355

N OH

O

N H

1011 (8E)-5,6-Dibromo-2′-N-demethyl-aplysinopsin Type: Indole-imidazole alkaloids. C13H10Br2N4O Yellow powder. Source: Sponge Hyrtios erecta (Okinawa). Pharm: Neuronal nitric oxide synthase inhibitor (selective). Ref: S. Aoki, et al, CPB, 2001, 49, 1372

Br

H N

8E

NH N

Br

O

N H

1012 (8Z)-5,6-Dibromo-2′-N-demethyl-aplysinopsin Type: Indole-imidazole alkaloids. C13H10Br2N4O Yellow powder. Source: Sponge Hyrtios erecta (Okinawa). Pharm: Neuronal nitric oxide synthase inhibitor (selective). Ref: S. Aoki, et al, CPB, 2001, 49, 1372 O Br Br

4'

8Z

5

N N 2'

6

N H

NH

1

1013 Didemnimide A Type: Indole-imidazole alkaloids. C15H10N4O2 Irregular orange needles (MeCN aq), mp 234–235 °C. Source: Ascidian Didemnum conchyliatum (Bahamas, from seagrass blades in mangrove habitats). Pharm: Antifeedant (predator deterrent). Ref: H. C. Vervoort, et al, JOC, 1997, 62, 1486│ T. V. Hughes, et al, Tet. Lett., 1998, 39, 9629 H N

O

O

NH 6

N H

N

1014 Didemnimide B 6-BromodidemnimideA Type: Indole-imidazole alkaloids. C15H9BrN4O2 Fine light orange needles (MeCN aq), mp 334–335 °C. Source: Ascidian Didemnum conchyliatum

356

3 Pyrrole Indole and Imidazole Alkaloids

(Bahamas, from seagrass blades in mangrove habitats). Pharm: Antifeedant (predator deterrent, fish). Ref: H. C. Vervoort, et al, JOC, 1997, 62, 1486│ T. V. Hughes, et al, Tet. Lett., 1998, 39, 9629 H N

O

O

NH Br

N

N H

6

1015 Didemnimide C Type: Indole-imidazole alkaloids. C16H12N4O2 Dark orange needles (MeCN aq), mp > 300 °C. Source: Ascidian Didemnum conchyliatum (Bahamas, from seagrass blades in mangrove habitats). Pharm: Antifeedant (fish). Ref: H. C, Vervoort, et al, JOC, 1997, 62, 1486 H N

O

O N N N H

1016 Didemnimide D Type: Indole-imidazole alkaloids. C16H11BrN4O2 Small dark orange needles (MeCN aq), mp > 250 °C. Source: Ascidian Didemnum conchyliatum (Bahamas, from seagrass blades in mangrove habitats). Pharm: Antifeedant (fish). Ref: H. C, Vervoort, et al, JOC, 1997, 62, 1486 H N

O

O N N Br

N H

1017 Discodermindole Type: Indole-imidazole alkaloids. C11H10Br2N4 Viscous oil, [α]D21 = −27° (c = 1, MeOH). Source: Lithistid sponge Discodermia polydiscus (depth of 185 m, off Chub Cay, Barry Is., Bahamas). Pharm: Cytotoxic (P388, IC50 = 1.8 μg/mL; A549, IC50 = 4.6 μg/mL; HT29, IC50 = 12 μg/mL). Ref: H. H. Sun, et al, JOC, 1991, 56, 4307

3.11 Indole-Imidazole Alkaloids

357

H N NH2

Br

N 6

N H

Br

1018 N-3′-Ethylaplysinopsin Type: Indole-imidazole alkaloids. C16H18N4O Yellowish gum. Source: Sponge Smenospongia aurea (Jamaica). Pharm: affinity for 5-HT2A and 5-HT2C receptors (high activity). Ref: J. -F. Hu, et al, JNP, 2002, 65, 476 8

N 2' N

1

6

N H

N

O

4'

1019 Halocyamine A Type: Indole-imidazole alkaloids. C27H28BrN7O5 [α]D26 = +5.2° (c = 0.5, MeOH). Source: Ascidian Halocynthia roretzi (haemocytes). Pharm: Antibacterial (gram-positive bacteria: Bacillus subtilis, MIC = 50 μg/mL; Bacillus megaterium MIC = 50 μg/mL; Bacillus cereus, MIC = 100 μg/mL); antifungal (yeast Cryptococcus neoformans, MIC = 100 μg/mL). Ref: K. Azumi, et al, Biochemistry, 1990, 29, 159 OH HO

O

H 2N

N H

H N

H N

O H N

Br

O

N N H

1020 Halocyamine B Type: Indole-imidazole alkaloids. C29H32BrN7O6 [α]D26 = +63.1° (c = 0.5, MeOH). Source: Ascidian Halocynthia roretzi (haemocytes). Pharm: Antibacterial; antifungal (yeasts). Ref: K. Azumi, et al, Biochemistry, 1990, 29, 159

358

3 Pyrrole Indole and Imidazole Alkaloids

OH OH H N N

O H 2N

H N

N H

N H

O

O

HO

Br

N H

1021 Herdmanine K Type: Indole-imidazole alkaloids. C16H14N4O5 Source: Ascidian Herdmania momus (Jeju I., S. Korea). Pharm: Transactivats PPAR-γ (cell-based luciferase reporter assay). Ref: J. L. Li, et al, JNP, 2012, 75, 2082│ J. L. Li, et al, JNP, 2013, 76, 815 O HO

H N O

N H

N N H

COOH

1022 6-Hydroxydiscodermindole Type: Indole-imidazole alkaloids. C11H10Br2N4O [α]D21 = −41.6° (c = 0.1, MeOH). Source: Lithistid sponge Discodermia polydiscus (north point of Acklins I., Bahamas; off Grand Bahama I.). Pharm: Cytotoxic (P388, IC50 = 12.4 μmol/L, inhibits cell proliferation). Ref: J. Cohen, et al, Pharm. Biol., 2004, 42, 59│ P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644–2682 (rev) H N NH2

Br

N 6

HO

N H

Br

1023 Isobromodeoxytopsentin 6-Bromotopsentin A Type: Indole-imidazole alkaloids. C20H13BrN4O Amorph. yellow, solidmp 225–230 °C. Source: Sponge Spongosorites genitrix (Korea Waters). Pharm: Cytotoxic (K562, LC50 = 2.1 μg/mL). Ref: J. Shin, et al, JNP, 1999, 62, 647 N

O

N H N H

6

N H

Br

3.11 Indole-Imidazole Alkaloids

359

1024 Isobromotopsentin Type: Indole-imidazole alkaloids. C20H13BrN4O2 Amorph. yellow solid, mp 225–228 °C. Source: Sponge Spongosorites sp. (Southern Australia). Pharm: Cytotoxic; antineoplastic; antiviral; antifungal. Ref: L. M. Murray, et al, Aust. J. Chem., 1995, 48, 2053 N 22

HO

O

N H

N H

N H Br

1025 Isoplysin A Type: Indole-imidazole alkaloids. C14H14N4O Yellow needles, mp 310 °C (dec). Source: Sponge Aplysina sp. (Okinawa). Pharm: Cytotoxic (weak). Ref: K. Kondo, et al, JNP, 1994, 57, 1008 8

N 2' 6

N

1

O

N H

N H

4'

1026 Meleagrin Type: Indole-imidazole alkaloids. C23H23N5O4 Pale yellow leaves (CHCl3 or CH2Cl2), mp 250 °C (dec), [α]D = −116° (c = 0.088, CHCl3). Source: Marine-derived fungus Penicillium sp. F23-2 (depth of 5080 m, sediment-borne), marine-derived fungus Penicillium chrysogenum, deep-sea fungus Penicillium commune SD-118 (sediment). Pharm: Cytotoxic (A549, IC50 = 19.9 μmol/L; HL60, IC50 = 7.4 μmol/L); tubulin polymerization inhibitor (arrests cell cycle through G2/M phase at 5 μmol/L and 10 μmol/L); cytotoxic (DU145, IC50 = 5.0 μg/mL); cytotoxic (HepG2, IC50 = 12 μg/mL, NCI-H460, IC50 = 22 μg/mL, HeLa, IC50 = 20 μg/mL, MDA-MB-231, IC50 = 11 μg/mL) (Shang, 2012); antibacterial (Staphylococcus aureus, MIC = 64 μg/mL) (Shang, 2012). Ref: G. Bringmann, et al, Tetrahedron, 2005, 61, 7252│ L. Du, et al, Tetrahedron, 2009, 65, 1033L. Du, et al, J. Antibiot., 2010, 63, 165│ Z. Shang, et al, Chin. J. Oceanol. Limnol., 2012, 30, 305 OH O N N N H O

N O

NH

360

3 Pyrrole Indole and Imidazole Alkaloids

1027 Meleagrin B Type: Indole-imidazole alkaloids. C43H53N5O6 Yellow solid (MeOH), [α]D20 = −28.4° (c = 0.2, MeOH). Source: Deep-sea fungus Penicillium sp. F23-2 (depth of 5080 m, sediment-borne). Pharm: Cytotoxic (SRB method: A549, IC50 = 2.7 μmol/L; Bel7402, IC50 = 1.8 μmol/L; MTT method: HL60, IC50 = 6.7 μmol/L; Molt4, IC50 = 2.9 μmol/L; induces HL60 apoptosis). Ref: L. Du, et al, Tetrahedron, 2009, 65, 1033│ L. Du, et al, J. Antibiot., 2010, 63, 165 OH O H H

N 14

N

N

N H

O

N O

O

OH

1028 Meleagrin D Type: Indole-imidazole alkaloids. C32H37N5O5 Yellow solid (MeOH), [α]D20 = −116° (c = 0.01, MeOH). Source: Deep-sea fungus Penicillium sp. F23-2 (deep ocean sediment, location unspecified). Pharm: Cytotoxic (A549, IC50 = 32.2 μmol/L; HL60, IC50 > 100 μmol/L). Ref: L. Du, et al, Tetrahedron, 2009, 65, 1033│ L. Du, et al, J. Antibiot., 2010, 63, 165 OH O N 14

N N H

O

O

N

N O

1029 Meleagrin E Type: Indole-imidazole alkaloids. C32H39N5O6 Yellow solid (MeOH), [α]D20 = −55° (c = 0.01, MeOH). Source: Deep-sea fungus Penicillium sp. F23-2 (deep ocean sediment, location unspecified). Pharm: Cytotoxic (A549, IC50 = 55.9 μmol/L; HL60, IC50 > 100 μmol/L). Ref: L. Du, et al, Tetrahedron, 2009, 65, 1033│ L. Du, et al, J. Antibiot., 2010, 63, 165 OH O N 14

N N H

O

O

N

N O

OH

3.11 Indole-Imidazole Alkaloids

361

1030 N-3′-Methylaplysinopsin Type: Indole-imidazole alkaloids. C15H16N4O Source: Sponge Aplysinopsis reticulata. Pharm: Monoamine oxidase inhibitor; serotonergic neurotransmission potentiator. Ref: J. Baird-Lambert, et al, Life Sci., 1980, 26, 1069│ J. -F. Hu, et al, JNP, 2002, 65, 476 8

N 2' N

1

6

N

O

N H

4'

1031 (±)-Polyandrocarpamide D Type: Indole-imidazole alkaloids. C12H11N3O3 Yellow amorph. solid. Source: Ascidian Polyandrocarpa sp., sponge Zyzza massalis. Pharm: Antibacterial; antifungal. Ref: N. Lindquist, et al, Tet. Lett., 1990, 31, 2521│ I. Mancini,et al, Helv. Chim. Acta, 1994, 77, 1886 O H

N

N

H

O

O

N H

1032 Trachycladindole A Type: Indole-imidazole alkaloids. C13H13BrN4O2 Amorph. solid, [α]D = +5.9° (c = 0.95, MeOH). Source: Sponge Trachycladus laevispirulifer. Pharm: Cytotoxic (A549, GI50 = 6.5 μmol/L, TGI = 9.2 μmol/L, LC50 = 20.8 μmol/L; HT29, GI50 = 2.9 μmol/L, TGI = 7.4 μmol/L, LC50 > 30 μmol/L; MDA-MB-231, GI50 = 1.2 μmol/L, TGI = 1.6 μmol/L, LC50 > 30 μmol/L). Ref: R. J. Capon, et al, Org. Biomol. Chem., 2008, 6, 2765

3'

NH

H N

N

4'

Br

O 5

N H

OH

1033 Trachycladindole B Type: Indole-imidazole alkaloids. C14H15BrN4O2 Amorph. solid, [α]D = +8.8° (c = 0.94, MeOH). Source: Sponge Trachycladus laevispirulifer. Pharm: Cytotoxic (A549, GI50 = 1.3 μmol/L, TGI = 2.0 μmol/L, LC50 = 5.4 μmol/L; HT29, GI50 = 0.5 μmol/L, TGI = 1.8 μmol/L, LC50 > 30 μmol/L; MDA-MB-231, GI50 = 2.7 μmol/L,

362

3 Pyrrole Indole and Imidazole Alkaloids

TGI = 5.1 μmol/L, LC50 > 30 μmol/L). Ref: R. J. Capon, et al, Org. Biomol. Chem., 2008, 6, 2765 NH N

3'

N

4'

Br

O 5

N H

OH

1034 Trachycladindole C Type: Indole-imidazole alkaloids. C13H13BrN4O3 Amorph. solid, [α]D = +2.9° (c = 1.3, MeOH). Source: Sponge Trachycladus laevispirulifer. Pharm: Cytotoxic (A549, GI50 = 19.8 μmol/L, TGI > 30 μmol/L, LC50 > 30 μmol/L; HT29, GI50 = 4.8 μmol/L, TGI = 18.1 μmol/L, LC50 > 30 μmol/L; MDA-MB-231, GI50 = 12.2 μmol/L, TGI > 30 μmol/L, LC50 > 30 μmol/L). Ref: R. J. Capon, et al, Org. Biomol. Chem., 2008, 6, 2765 3'

NH

H N

N

4'

Br

O 5

N H

HO

OH

1035 Trachycladindole D Type: Indole-imidazole alkaloids. C14H15BrN4O3 Amorph. solid, [α]D = +7.5° (c = 1, MeOH). Source: Sponge Trachycladus laevispirulifer. Pharm: Cytotoxic (A549, GI50 = 1.7 μmol/L, TGI = 1.9 μmol/L, LC50 > 30 μmol/L; HT29, GI50 = 0.4 μmol/L, TGI = 0.9 μmol/L, LC50 > 30 μmol/L; MDA-MB-231, GI50 = 2.4 μmol/L, TGI = 5.7 μmol/L, LC50 > 30 μmol/L). Ref: R. J. Capon, et al, Org. Biomol. Chem., 2008, 6, 2765 NH 3'

N N

4'

Br

O 5

HO

N H

OH

1036 Trachycladindole E Type: Indole-imidazole alkaloids. C14H15BrN4O3 Amorph. solid, [α]D = +11.6° (c = 0.48, MeOH). Source: Sponge Trachycladus laevispirulifer. Pharm: Cytotoxic (A549, GI50 = 0.5 μmol/L, TGI = 0.7 μmol/L, LC50 = 2.1 μmol/L; HT29, GI50 = 0.3 μmol/L, TGI = 0.8 μmol/L, LC50 > 30 μmol/L; MDA-MB-231, GI50 = 1.1 μmol/L,

3.12 Indolactam Alkaloids

363

TGI = 2.1 μmol/L, LC50 = 9.0 μmol/L). Ref: R. J. Capon, et al, Org. Biomol. Chem., 2008, 6, 2765 NH 3'

N 4'

HO

N

Br

O 5

N H

OH

1037 Trachycladindole F Type: Indole-imidazole alkaloids. C14H15BrN4O4 Amorph. solid, [α]D = −4.8° (c = 0.94, MeOH). Source: Sponge Trachycladus laevispirulifer. Pharm: Cytotoxic (A549, GI50 = 1.2 μmol/L, TGI = 1.7 μmol/L, LC50 > 30 μmol/L; HT29, GI50 = 0.8 μmol/L, TGI = 1.8 μmol/L, LC50 > 30 μmol/L; MDA-MB-231, GI50 = 2.3 μmol/L, TGI = 3.6 μmol/L, LC50 > 30 μmol/L). Ref: R. J. Capon, et al, Org. Biomol. Chem., 2008, 6, 2765 NH 3'

N 4'

HO Br

N O

5 6

N H

HO

OH

3.12 Indolactam Alkaloids 1038 N13-Demethylteleocidin A1 Type: Indolactam alkaloids. C26H37N3O2 Source: Marine-derived streptomycete Streptomyces sp. NBRC 105896. Pharm: Tumour promoter. Ref: K. Irie, et al, Agric. Biol. Chem., 1988, 52, 3193

H N

HN O

26

24

N H

OH

364

3 Pyrrole Indole and Imidazole Alkaloids

1039 Indolactam V Type: Indolactam alkaloids. C17H23N3O2 Needles (EtOH aq) or amorph. solid, mp 130–165 °C, [α]D27 = −170° (c = 0.499, EtOH). Source: Marine-derived streptomycete Streptomyces sp. NBRC 105896. Pharm: Antiviral (induces early antigen of EpsteinBarr virus); CSF inducer; PKC activator; tumour promoter; biosynthetic intermed. of teleocidins. Ref: K. Irie, et al, Agric. Biol. Chem., 1984, 48, 1269

H N N

12

OH

9

O 7

N H

1040 JBIR 31 2-Oxoteleocidin A1 Type: Indolactam alkaloids. C27H39N3O3 Amorph. solid, mp 58– 62 °C, [α]D25 = −226.3° (c = 0.02, MeOH). Source: Marine-derived streptomycete Streptomyces sp. NBRC 105896 from sponge Haliclona sp. (Tateyama City, Chiba, Japan). Pharm: Cytotoxic (HeLa, IC50 = 49 μmol/L, ACC-MESO-1, IC50 = 88 μmol/ L). Ref: M. Izumikawa, et al, J. Antibiot., 2010, 63, 33 O H N N H

OH 3 2

26

24

19

O

N H

1041 Lyngbyatoxin A Teleocidin A1 Type: Indolactam alkaloids. C27H39N3O2 mp 61 °C, [α]D = −171° (c = 1.8, CHCl3), [α]D = −110° (MeOH). Source: Cyanobacterium Lyngbya majuscula (Shallowwater, lipid extracts, Hawaiian), marine-derived streptomycete Streptomyces sp. NBRC 105896. Pharm: Nematocide; acaricide; antineoplastic (inhibits leukemia); highly inflammatory and vesicatory; tumour promoter; causes dermatitis; very toxic; LD50 (mus, orl) = 2 mg/kg. Ref: J. H. Cardellina, et al, Science (Washington, D. C.), 1979, 204, 193│ S. -I. Sakai, et al, Tet. Lett., 1986, 27, 5219

3.12 Indolactam Alkaloids

H N

365

OH

N O

N H

24

26

1042 Lyngbyatoxin B Type: Indolactam alkaloids. C27H39N3O3 Amorph. Source: Cyanobacterium Lyngbya majuscula. Pharm: TPA binding inhibitor; skin irritant. Ref: N. Aimi, et al, JNP, 1990, 53, 1593

H N

OH

N O

N H

OH 26 24

1043 Lyngbyatoxin C Type: Indolactam alkaloids. C27H39N3O3 Amorph. Source: Cyanobacterium Lyngbya majuscula. Pharm: TPA binding inhibitor; skin irritant. Ref: N. Aimi, et al, JNP, 1990, 53, 1593

H N N

OH

O

HO

24

N H

26

1044 Ambiguine H isonitrile Type: Indoloterpenoid alkaloids. C25H32N2 Amorph. solid, [α]D25 = −65° (c = 0.51, MeOH). Source: Cyanobacterium Fischerella sp. (Israel). Pharm: Antibacterial (Staphylococcus albus and Bacillus subtilis, MIC = 0.08–1.25 μg/mL). Ref: A. Raveh, et al, JNP, 2007, 70, 196

366

3 Pyrrole Indole and Imidazole Alkaloids

NC

H

N H

3.13 Indoloterpenoid Alkaloids 1045 Ambiguine I isonitrile Type: Indoloterpenoid alkaloids. C26H30N2O2 Amorph. solid, [α]D25 = −39° (c = 0.29, MeOH). Source: Cyanobacterium Fischerella sp. (Israel). Pharm: Antibacterial (Escherichia coli ESS K-12, Staphylococcus albus and Bacillus subtilis, MIC = 0.08– 1.25 μg/mL). Ref: A. Raveh, et al, JNP, 2007, 70, 196

OH H

NC

O

N H

1046 α-Cyclopiazonic acid Type: Indoloterpenoid alkaloids. C20H20N2O3 Yellow amorph. solid, [α]D20 = −92.1° (c = 0.1, CHCl3), mp 245–246 °C, [α]D18 = −74° (c = 1, CHCl3). Source: Marine-derived fungus Aspergillus flavus C-F-3 from green alga Enteromorpha tubulosa (Putian Pinghai, China), terrestrial fungi (Penicillium spp. and Aspergillus spp.). Pharm: Cytotoxic (HL60, IC50 = 2.4 μmol/L; Molt4, IC50 = 12.3 μmol/L; Bel7402, IC50 = 17.5 μmol/L; A549, IC50 = 21.5 μmol/L). Ref: A. -Q. Lin, et al, Chem. Nat. Compd. (Engl. Transl.), 2009, 45, 677│ W. P. Norred, et al, J. Agric. Food Chem., 1988, 36, 113 O

OH

N H H

H

N H

O

3.13 Indoloterpenoid Alkaloids

367

1047 Hapalindole A Type: Indoloterpenoid alkaloids. C21H23ClN2 Yellow plates (CH2Cl2/heptane), mp 160– 167 °C (dec), [α]D25 = −78° (c = 1.2, CH2Cl2). Source: Cyanobacterium Hapalosiphon fontinalis. Pharm: Antibacterial; antimycotic; algicide. Ref: R. E. Moore, et al, JOC, 1987, 52, 1036 Cl 21 6a

H

9 20

10a

H

NC

N H

1048 12-epi-Hapalindole C Type: Indoloterpenoid alkaloids. C21H24N2 [α]D = +10.4° (c = 0.54, CH2Cl2). Source: Cyanobacteria Hapalosiphon welwitschii, Hapalosiphon laingii and Westiella intricata. Pharm: Ichthyotoxic. Ref: K. Stratmann,et al, JACS, 1994, 116, 9935 5'

H

H

NC

N H

1049 12-epi-Hapalindole E Type: Indoloterpenoid alkaloids. C21H23ClN2 [α]D = +42.9° (c = 0.3, CH2Cl2). Source: Cyanobacteria Hapalosiphon welwitschii, Hapalosiphon laingii and Westiella intricata. Pharm: Ichthyotoxic. Ref: K. Stratmann,et al, JACS, 1994, 116, 9935 Cl 5'

H

H

NC

N H

1050 12-epi-Hapalindole G Type: Indoloterpenoid alkaloids. C21H23ClN2 Source: Cyanobacterium Hapalosiphon laingii (from surface of dead coral, Papua New Guinea). Pharm: Ichthyotoxin. Ref: D. Klein, et al, JNP, 1995, 58, 1781

368

3 Pyrrole Indole and Imidazole Alkaloids

Cl

H NC

H

N H

1051 12-epi-Hapalindole H Type: Indoloterpenoid alkaloids. C21H24N2 mp 187–189 °C, [α]D25 = +217.3° (c = 0.163, CH2Cl2). Source: Cyanobacterium Hapalosiphon laingii (from surface of dead coral, Papua New Guinea). Pharm: Ichthyotoxin. Ref: D. Klein, et al, JNP, 1995, 58, 1781

H NC

H

NH

1052 12-epi-Hapalindole J Type: Indoloterpenoid alkaloids. C21H24N2 Amorph. solid. Source: Cyanobacterium Fischerella sp. ATCC43239. Pharm: Insecticide. Ref: P. G. Becher, et al, Phytochemistry, 2007, 68, 2493 21 6a

H

H

9 20

10a

NC

N H

1053 12-epi-Hapalindole Q Type: Indoloterpenoid alkaloids. C21H24N2 Source: Cyanobacterium Hapalosiphon laingii (from surface of dead coral, Papua New Guinea). Pharm: Ichthyotoxin. Ref: D. Klein, et al, JNP, 1995, 58, 1781

H

H

NH

NC

3.13 Indoloterpenoid Alkaloids

369

1054 Hapalindole T Type: Indoloterpenoid alkaloids. C21H23ClN2OS [α]D26 = −137° (c = 1.5, CH2Cl2). Source: Cyanobacterium Hapalosiphon fontinalis ATCC39964. Pharm: Antibacterial; antimycotic. Ref: R. E. Moore, et al, JOC, 1987, 52, 1036 Cl

NH H

S

O

N H

1055 Hapalindolinone A Type: Indoloterpenoid alkaloids. C21H21ClN2O Cryst., mp 92–96 °C (dec), [α]D25 = −30°. Source: Cyanobacteria Fischerella sp. (cultured) and Hapalosiphon laingii. Pharm: Adenylate cyclase inhibitor; vasopressin antagonist; ichthyotoxin. Ref: R. E. Schwartz, et al, JOC, 1987, 52, 3704 Cl H

CN H O N H

1056 Hapalindolinone B Type: Indoloterpenoid alkaloids. C21H22N2O Oil. Source: Cyanobacterium Fischerella sp. (cultured). Pharm: Adenylate cyclase inhibitor. Ref: R. E. Schwartz, et al, JOC, 1987, 52, 3704

CN H O N H

1057 Iso-α-cyclopiazonic acid 5-epi-α-Cyclopiazonic acid. Type: Indoloterpenoid alkaloids. C20H20N2O3 Amorph. yellow solid, [α]D20 = +323.5° (c = 0.15, CHCl3). Source: Marine-derived fungus Aspergillus flavus C-F-3 from green alga Enteromorpha tubulosa (Putian Pinghai, China). Pharm: Cytotoxic (HL60, IC50 = 90.0 μmol/L; Molt4, IC50 = 68.6 μmol/L;

370

3 Pyrrole Indole and Imidazole Alkaloids

Bel7402, IC50 > 100 μmol/L; A549, IC50 = 42.2 μmol/L). Ref: A. -Q. Lin, et al, Chem. Nat. Compd. (Engl. Transl.), 2009, 45, 677 O

OH

N H H

H

O

N H

1058 Stachyin B Type: Indoloterpenoid alkaloids. C46H61NO8 Source: Marine fungus Stachybotrys sp. MF347. Pharm: Antibacterial (three gram-positive bacterial strains, MRSA, IC50 = 1.75 μmol/L; B. subtilis, IC50 = 1.42 μmol/L; S. epidermidis, IC50 = 1.02 μmol/L). Ref: B. Wu, et al, Mar. Drugs, 2014, 12, 1924 H

HO

H

OH

O O

HO N O

OH O

First dimeric spirodihydrobenzofuranlactams with N-C linkage

3.14 Penitrems 1059 Antibiotic JBIR 03 Type: Penitrems. C28H37NO Needles, mp 142.5–148 °C, [α]D24 = +46.2° (c = 0.05, MeOH). Source: Marine-derived fungi Dichotomomyces cejpii var. cejpii NBRC 103559 and Aspergillus oryzae. Pharm: Antifungal; antibacterial (MRSA). Ref: M. Ogata, et al, J. Antibiot., 2007, 60, 645│ M. -F. Qiao, et al, BoMCL, 2010, 20, 5677 H

H N H

H O H

3.14 Penitrems

371

1060 6-Bromopenitrem B Type: Penitrems. C37H44BrNO5 Source: Marine-derived fungus Penicillium commune isolate GS20 (supplemented with potassium bromide). Pharm: Anti-invasive (significant); cytotoxic (antiproliferative activity against MCF7 and MDA-MB-231 tumor cell lines). Ref: A. A. Sallam, et al, Med. Chem. Comm, 2013, 4, 1360 H H

O

H

H O Br

OH

OH

N H

H

O

1061 Dehydroxypaxilline Type: Penitrems. C27H33NO3 Source: Mangrove-derived fungus Penicillium camemberti OUCMDZ-1492 from mangrove Rhizophora apiculata (soil, Wenchang, Hainan Province, China). Pharm: Antiviral (Influenza A H1N1 Virus, IC50 > 150 μmol/L, control Ribavirin, IC50 = (113.1 ± 5.0)μmol/L). Ref: Y. Fan, et al, JNP, 2013, 76, 1328 H O H

N H

H

O

H

OH

1062 4a-Demethylpaspaline-4a-carboxylic acid Type: Penitrems. C28H37NO4 White, amorphous powder, [α]D25 = −54° (c = 0.1, CHCl3). Source: Mangrove-derived fungus Penicillium camemberti OUCMDZ-1492 from mangrove Rhizophora apiculata (soil, Wenchang, Hainan Province, China). Pharm: Antiviral (Influenza A H1N1 Virus, IC50 = (38.9 ± 1.3)μmol/L, control Ribavirin, IC50 = (113.1 ± 5.0)μmol/L). Ref: Y. Fan, et al, JNP, 2013, 76, 1328 H O

N H

OH

H H

O

H

OH

1063 4a-Demethylpaspaline-3,4,4a-triol Type: Penitrems. C27H33NO5 White, amorphous powder, [α]D25 = −91° (c = 0.2, CHCl3). Source: Mangrove-derived fungus Penicillium camemberti OUCMDZ-1492 from

372

3 Pyrrole Indole and Imidazole Alkaloids

mangrove Rhizophora apiculata (soil, Wenchang, Hainan Province, China). Pharm: Antiviral (Influenza A H1N1 Virus, IC50 = (32.2 ± 3.1)μmol/L, control Ribavirin, IC50 = (113.1 ± 5.0)μmol/L). Ref: Y. Fan, et al, JNP, 2013, 76, 1328 H O OH

N H

H

O

H

OH

HO

1064 3-Deoxo-4b-deoxypaxilline Type: Penitrems. C27H35NO2 Colorless crystals, mp 296–298 °C, [α]D25 = −59° (c = 0.3, CHCl3). Source: Mangrove-derived fungus Penicillium camemberti OUCMDZ-1492 from mangrove Rhizophora apiculata (soil, Wenchang, Hainan Province, China). Pharm: Antiviral (Influenza A H1N1 Virus, IC50 = (28.3 ± 1.0)μmol/L, control Ribavirin, IC50 = (113.1 ± 5.0)μmol/L). Ref: Y. Fan, et al, JNP, 2013, 76, 1328 H

H

N H

H

O

H

OH

1065 9,10-Diisopentenylpaxilline Type: Penitrems. C37H49NO3 White, amorphous powder, [α]D25 = −44° (c = 0.2, CHCl3). Source: Mangrove-derived fungus Penicillium camemberti OUCMDZ-1492 from mangrove Rhizophora apiculata (soil, Wenchang, Hainan Province, China). Pharm: Antiviral (Influenza A H1N1 Virus, IC50 = (73.3 ± 2.1)μmol/L, control Ribavirin, IC50 = (113.1 ± 5.0)μmol/L). Ref: Y. Fan, et al, JNP, 2013, 76, 1328

H O N H

H O

OH

1066 Emindole DA Type: Penitrems. C28H39NO Prisms (C6H6/hexane), mp 146–147 °C, [α]D = −30.7° (c = 2.32, MeOH). Source: Marine-derived fungus Emericella nidulans var. acristata from an unidentified green alga, marine-derived fungi Emericella desertorum

3.14 Penitrems

373

(Mediterranean Sea) and Emericella striata. Pharm: Cytotoxic (in vitro survival and proliferation assay, panel of 36 hmn tumor, mean IC50 value = 5.5 μg/mL, control Adriamycin, IC50 = 0.016 μg/mL; 10 μg/mL, 33 out of 36 cell lines (92%) were inhibited); mycotoxin. Ref: K. Nozawa, et al, JCS Perkin I, 1988, 1689; 2155│ Kralj, et al, JNP, 2006, 69, 995

OH H

N H

1067 Emindole SB Type: Penitrems. C28H39NO Amorph. powder, mp 58–60 °C, [α]D15 = +32° (c = 0.79, MeOH); colorless crystals, mp 68–70 °C, [α]D25 = −19° (c = 0.2, CHCl3) (Fan, 2013). Source: Marine-derived fungus Aspergillus oryzae, mangrove-derived unidentified fungus dz17 from an unidentified mangrove, mangrove-derived fungus Penicillium camemberti OUCMDZ-1492 from mangrove Rhizophora apiculata (soil, Wenchang, Hainan Province, China) (Fan, 2013). Pharm: Antiviral (Influenza A H1N1 Virus, IC50 = (26.2 ± 0.3)μmol/L, control Ribavirin, IC50 = (113.1 ± 5.0)μmol/L) (Fan, 2013). Ref: K. Nozawa, et al, JCS Perkin I, 1988, 2607│ Z. Huang, et al, Chem. Nat. Compd. (Engl. Transl.), 2007, 43, 655│ Y. Fan, et al, JNP, 2013, 76, 1328 H

H

N H

OH

1068 Emindole SB β-mannoside Type: Penitrems. C35H51NO5 Source: Marine-derived fungus Dichotomomyces cejpii. Pharm: Cannabinoid receptor CB2 antagonist (Ki = 10.6 μmol/L), Ref: H. Harms, et al, JNP, 2014, 77, 673 H H N H HO HO HO

OH

O

374

3 Pyrrole Indole and Imidazole Alkaloids

1069 2′-Hydroxypaxilline Type: Penitrems. C27H33NO5 White, amorphous powder, [α]D25 = −10° (c = 0.3, CHCl3). Source: Mangrove-derived fungus Penicillium camemberti OUCMDZ-1492 from mangrove Rhizophora apiculata (soil, Wenchang, Hainan Province, China). Pharm: Antiviral (Influenza A H1N1 Virus, IC50 = (124.7 ± 9.4)μmol/L, control Ribavirin, IC50 = (113.1 ± 5.0)μmol/L). Ref: Y. Fan, et al, JNP, 2013, 76, 1328 H

O OH

N H

H

O H

OH OH

1070 19-Hydroxypenitrem A Type: Penitrems. C37H44ClNO7 White amorphous solid, [α]D25 = −40.0° (c = 0.16, MeOH). Source: Marine-derived fungus Aspergillus nidulans EN-330 (endophytic) from red alga. Pharm: Antibacterial (Edwardsiella tarda, MIC = 16 μg/mL, Vibrio anguillarum, MIC = 32 μg/mL, Escherichia coli, MIC = 16 μg/mL, Staphylococcus aureus, MIC = 16 μg/mL); toxic (brine shrimp Artemia salina bioassay, LD50 = 3.2 μmol/L). Ref: P. Zhang, et al, Phytochem. Lett., 2015, 12, 182 H H

O

OH

OH O N H

Cl

OH

OH H

O

1071 19-Hydroxypenitrem E Type: Penitrems. C37H45NO7 White amorphous solid, [α]D25 = −41.6° (c = 0.11, MeOH). Source: Marine-derived fungus Aspergillus nidulans EN-330 (endophytic) from red alga. Pharm: Toxic (brine shrimp Artemia salina bioassay, LD50 = 4.6 μmol/L). Ref: P. Zhang, et al, Phytochem. Lett., 2015, 12, 182 H H

O

OH

OH O N H

OH

OH H

O

3.14 Penitrems

375

1072 (6S,7R,10E,14E)-16-(1H-Indol-3-yl)-2,6,10,14-tetramethylhexadeca2,10,14-triene-6,7-diol Type: Penitrems. C28H41NO2 Brown oil, [α]D25 = −9.7° (c = 0.5, CHCl3). Source: Mangrove-derived fungus Penicillium camemberti OUCMDZ-1492 from mangrove Rhizophora apiculata (soil, Wenchang, Hainan Province, China). Pharm: Antiviral (Influenza A H1N1 Virus, IC50 = (34.1 ± 6.4)μmol/L, control Ribavirin, IC50 = (113.1 ± 5.0)μmol/L). Ref: Y. Fan, et al, JNP, 2013, 76, 1328

OH N H

OH

1073 21-Isopentenylpaxilline 9-Isopentenylpaxilline Type: Penitrems. C32H41NO4 Oil, [α]D = −12° (c = 0.30, CHCl3). Source: Mangrove-derived fungus Penicillium camemberti OUCMDZ-1492 from mangrove Rhizophora apiculata (soil, Wenchang, Hainan Province, China), terrestrial fungus Eupenicillium shearii NRRL3324. Pharm: Antiviral (Influenza A H1N1 Virus, IC50 = (6.6 ± 0.3)μmol/L, control Ribavirin, IC50 = (113.1 ± 5.0)μmol/L); insecticide; mycotoxin. Ref: G. N. Belofsky, et al, Tetrahedron, 1995, 51, 3959│ A. B. Smith, et al, Helv. Chim. Acta, 2003, 86, 3908│ Y. Fan, et al, JNP, 2013, 76, 1328 H

O OH

N H

H

O

H

OH

1074 27-O-Methylasporyzine C Type: Penitrems. C29H41NO2 Source: Marine-derived fungus Dichotomomyces cejpii. Pharm: GPR18 (G-protein coupled receptor 18, N-arachidonyl glycine receptor) antagonist (IC50 = 13.4 μmol/L). Ref: H. Harms, et al, JNP, 2014, 77, 673 H O H N H

OH

1075 Paspaline Type: Penitrems. C28H39NO2 Source: Mangrove-derived fungus Penicillium camemberti OUCMDZ-1492 from mangrove Rhizophora apiculata (soil, Wenchang, Hainan Province,

376

3 Pyrrole Indole and Imidazole Alkaloids

China). Pharm: Antiviral (Influenza A H1N1 Virus, IC50 = (77.9 ± 8.2)μmol/L, control Ribavirin, IC50 = (113.1 ± 5.0)μmol/L). Ref: Y. Fan, et al, JNP, 2013, 76, 1328 H

H

N H

H

O

H

OH

1076 Paspalitrem A Type: Penitrems. C32H39NO4 Source: Mangrove-derived fungus Penicillium sp. HKI0459 from mangrove Aegiceras corniculatum (China Waters). Pharm: Tremorgenic mycotoxin; LD50 (mus, ipr) < 14 mg/kg. Ref: M. Xu, et al, Tetrahedron, 2007, 63, 435

H OH N H

O

O O

1077 Paxilline Type: Penitrems. C27H33NO4 Source: Mangrove-derived fungus Penicillium camemberti OUCMDZ-1492 from mangrove Rhizophora apiculata (soil, Wenchang, Hainan Province, China). Pharm: Antiviral (Influenza A H1N1 Virus, IC50 = (17.7 ± 0.9)μmol/L, control Ribavirin, IC50 = (113.1 ± 5.0)μmol/L). Ref: Y. Fan, et al, JNP, 2013, 76, 1328 H O N H

OH H

O

H

OH

1078 Shearinine A Type: Penitrems. C37H45NO5 mp 250 °C (dec), [α]D = +16° (c = 0.20, CHCl3). Source: Marine-derived fungi Penicillium sp. HKI0459 and Penicillium janthinellum, isolated from the sclerotioid ascostromata of Eupenicillium shearii. Pharm: Induces apoptosis (hmn leukemia cell line HL60); insecticidal (Helicoverpa zea, Carpophilus hemipterus and Spodoptera frugiperda); inhibitor of large-conductance Calcium-activated Potassium channels; antiinsectan activity. Ref: G. N. Belofsky, et al, Tetrahedron, 1995, 51, 3959│ M. Xu, et al, Tetrahedron, 2007, 63, 435│ O. F. Smetanina, et al, JNP, 2007, 70, 906│ G. N. Belofsky, et al, U.S. Patent 5,492,902 A, 20 February 1996

3.14 Penitrems

377

H OH

H

O

22 23

28

N H

O

O

O

1079 Shearinine B Type: Penitrems. C37H47NO5 Source: isolated from the sclerotioid ascostromata of Eupenicillium shearii. Pharm: Insecticidal (Helicoverpa zea, Carpophilus hemipterus and Spodoptera frugiperda). Ref: G. N. Belofsky, et al, Tetrahedron, 1995, 51, 3959│ G. N. Belofsky, et al, U.S. Patent 5,492,902 A, 20 February 1996 H H

OH

O

22

O

23

10

N H

28

34

H

O

35

OH

1080 Shearinine C Type: Penitrems. C37H47NO7 Source: isolated from the sclerotioid ascostromata of Eupenicillium shearii. Pharm: Insecticidal (Helicoverpa zea, Carpophilus hemipterus and Spodoptera frugiperda). Ref: G. N. Belofsky, et al, Tetrahedron, 1995, 51, 3959│ G. N. Belofsky, et al, U.S. Patent 5,492,902 A, 20 February 1996 O H H OH O

N H

O H

O

O

OH

1081 22α-Shearinine D 22α-Hydroxy-shearinine A Type: Penitrems. C37H45NO6 Amorph. powder, [α]D = +67.7° (c = 0.3, CHCl3); cryst. (hexane/EtOAc), mp > 300 °C (dec), [α]D20 = +3.5° (c = 0.17, CHCl3). Source: Marine-derived fungi Penicillium sp. HKI0459 (endophytic) from mangrove Aegiceras corniculatum (China Waters) and Penicillium janthinellum from sediment (Russia). Pharm: Induces apoptosis (hmn leukemia cell line HL60); inhibitor of large-conductance Calcium-activated Potassium channels; inhibits biofilm formation (Candida albicans). Ref: M. Xu, et al, Tetrahedron, 2007, 63, 435│ O. F. Smetanina, et al, JNP, 2007, 70, 906; 2054│ J. You, et al, ACS Chem. Biol., 2013, 8, 840

378

3 Pyrrole Indole and Imidazole Alkaloids

H HO OH

H

O

22 28

23

N H

O

O

O

1082 Shearinine E (Smetanina, 2007) Type: Penitrems. C37H45NO6 Source: Marine-derived fungus Penicillium janthinellum (sediment, Russia). Pharm: Inducer of apoptosis (HL60 cells). Ref: O. F. Smetanina, et al, JNP, 2007, 70, 906; 2054 H

H OH

OH

H

O

22 23

N H

O

O

O

H-22, H-23 trans

1083 Shearinine E (Xu, 2007) 22α-Methoxy-shearinine A Type: Penitrems. C38H47NO6 Amorph. powder, [α]D = +8.9° (c = 0.2, CHCl3). Source: Mangrove-derived fungus Penicillium sp. HKI0459 (endophytic)from mangrove Aegiceras corniculatum (China Waters). Pharm: Induces apoptosis (hmn leukemia cell line HL60); inhibits EGF-induced malignant transformation of JB6 P+ Cl 41 cells; inhibitor of large-conductance Calciumactivated Potassium channels; inhibits biofilm formation (Candida albicans). Ref: M. Xu, et al, Tetrahedron, 2007, 63, 435│ O. F. Smetanina, et al, JNP, 2007, 70, 906│ J. You, et al, ACS Chem. Biol., 2013, 8, 840 H O H O

OH 22 23 28

N H O

O

O

1084 Shearinine F (Smetanina, 2007) Type: Penitrems. C37H45NO6 Source: Marine-derived fungus Penicillium janthinellum (sediment, Russia). Pharm: Inducer of apoptosis (HL60 cells); inhibits EGF-induced malignant transformation (JB6 P+ CI41, potential cancer preventive effect). Ref: O. F. Smetanina, et al, JNP, 2007, 70, 906; 2054

3.15 Isoindole Alkaloids

H

379

H

H OH

OH N H

O

O

O

O

1085 Shearinine G Type: Penitrems. C37H43NO6 Amorph. powder, [α]D = +35.7° (c = 0.1, CHCl3). Source: Mangrove-derived fungus Penicillium sp. HKI0459 (endophytic) from mangrove Aegiceras corniculatum. Pharm: Inhibitor of large-conductance Calcium-activated Potassium channels. Ref: M. J. Xu, et al, Tetrahedron, 2007, 63, 435 H O 23

O

OH 22

N H

28

O

O

O

3.15 Isoindole Alkaloids 1086 Conioimide Type: Isoindole alkaloids. C15H15NO4 Source: Marine-derived fungus Coniothyrium cereale from green alga Enteromorpha sp. (Fehmarn I., Baltic Sea, Germany). Pharm: Selective inhibition of hmn leukocyte elastase. Ref: M. F. Elsebai, et al, EurJOC, 2012, 31, 6197

O

H N

O

HO O

1087 Emerimidine A Type: Isoindole alkaloids. C10H11NO4 Source: Mangrove-derived fungus Emericella sp. from mangrove Aegiceras corniculatum (Haikou, Hainan, China). Pharm: Antiviral (IFV H1N1, IC50 = 201.1 μmol/L, moderate). Ref: G. Zhang, et al, Phytochemistry, 2011, 72, 1436│ S. Z. Moghadamtousi, et al, Mar. Drugs, 2015, 13, 4520 (rev)

380

3 Pyrrole Indole and Imidazole Alkaloids

O O NH O OH

1088 Emerimidine B Type: Isoindole alkaloids. C10H11NO4 Source: Mangrove-derived fungus Emericella sp. from mangrove Aegiceras corniculatum (Haikou, Hainan, China). Pharm: Antiviral (IFV H1N1, IC50 = 296.62 μmol/L, moderate). Ref: G. Zhang, et al, Phytochemistry, 2011, 72, 1436│ S. Z. Moghadamtousi, et al, Mar. Drugs, 2015, 13, 4520 (rev) O O NH HO O

1089 Mariline A1 Type: Isoindole alkaloids. C33H43NO5 Colorless oil, [α]D23 = +14° (c = 0.225, acetone). Source: Marine-derived fungus Stachylidium sp. from sponge Callyspongia cf. flammea (location unspecified). Pharm: HLE inhibitor (IC50 = 0.86 μmol/L, HLE is a primary source of tissue damage with inflammatory diseases such as chronic obstructive pulmonary disease, cystic fibrosis, and adult respiratory distress syndrome); cytotoxic ( five cancer cells, mean GI50 = 24.4 μmol/L); antiplasmodial (liver stage of Plasmodium berghei, IC50 = 6.68 μmol/L); antitrypanosomal (Trypanosoma brucei brucei, IC50 = 17.7 μmol/L); antileishmanial (Leishmania major, IC50 > 100 μmol/L). Ref: C. Almeida, et al, Chem. -Eur. J., 2012, 18, 8827 O O

N O

O

O

1090 Mariline A2 Type: Isoindole alkaloids. C33H43NO5 Colorless oil, [α]D23 = −14° (c = 0.175, acetone). Source: Marine-derived fungus Stachylidium sp. from sponge Callyspongia cf. flammea (location unspecified). Pharm: HLE inhibitor (IC50 = 0.86 μmol/L, HLE is a primary source of tissue damage with inflammatory diseases such as chronic obstructive pulmonary disease, cystic fibrosis, and adult respiratory distress syndrome); cytotoxic ( 19 cancer, mean GI50 = 11.02 μmol/L); antiplasmodial (liver stage of Plasmodium berghei, IC50 = 11.61 μmol/L); antagonistic (histamine receptor

3.15 Isoindole Alkaloids

381

H2, Ki = 5.92 μmol/L, dopamine receptor DAT, Ki = 5.63 μmol/L, adrenergic receptor β3, Ki = 5.63 μmol/L). Ref: C. Almeida, et al, Chem. -Eur. J., 2012, 18, 8827 O O

N O

O

O

1091 Mariline B Type: Isoindole alkaloids. C22H33NO4 White amorph. solid. Source: Marine-derived fungus Stachylidium sp. from sponge Callyspongia cf. flammea (location unspecified). Pharm: Antiplasmodial (liver stage of Plasmodium berghei, IC50 = 13.84 μmol/L); antagonistic (cannabinoid receptor CB2, Ki = 5.97 μmol/L). Ref: C. Almeida, et al, Chem. -Eur. J., 2012, 18, 8827

O N OH O

O

1092 Mariline C Type: Isoindole alkaloids. C11H13NO3 Amorph. solid. Source: Marine-derived fungus Stachylidium sp. from sponge Callyspongia cf. flammea (location unspecified). Pharm: Antagonistic (cannabinoid receptor CB2, Ki = 5.94 μmol/L). Ref: C. Almeida, et al, Chem. -Eur. J., 2012, 18, 8827

OH H

N O

O

1093 5-Methoxy-2,6-dimethyl-2H-isoindole-4,7-dione Type: Isoindole alkaloids. C11H11NO3 mp 153–154 °C. Source: Sponge Reniera sp. Pharm: Antibacterial (gram-positive bacteria, marine bacterium Pseudomonas spp.). Ref: J. M. Frincke, et al, JACS, 1982, 104, 265│ K, A. Parker, et al, Tet. Lett., 1984, 25, 4917

382

3 Pyrrole Indole and Imidazole Alkaloids

O N O O

1094 Stachybotrin D Type: Isoindole alkaloids. C26H35NO5 Source: Marine-derived fungus Stachybotrys chartarum from sponge Xestospongia testudinaria (Xisha Is., South China Sea, China). Pharm: Anti-HIV-1 (inhibits replication of HIV-1 by targeting reverse transcriptase and blocks non-nucleoside reverse transcriptase inhibitor-resistant strains as well). Ref: X. Ma, et al, JNP, 2013, 76, 2298 O N O

HO O

HO

H

1095 Stachyflin Type: Isoindole alkaloids. C23H31NO4 Source: Marine-derived fungus Stachybotrys sp. RF-7260. Pharm: Anti-HIV (inhibition of fusion between the viral envelope and the endosome). Ref: S. Yagi, et al, Pharmaceut. Res., 1999, 16, 1041│ K. Minagawa, et al, J. Antibiot., 2002, 55, 155 O HN OH O

HO

H

3.16 Miscellaneous Indole Alkaloids

383

3.16 Miscellaneous Indole Alkaloids 1096 14-O-(N-Acetylglucosaminyl) teleocidin A GlcNAc-TA Type: Miscellaneous indole alkaloids. C35H52N4O7 Powder, [α]D = +130.2° (c = 0.15, MeOH). Source: Streptomycete Streptomyces sp. MM216-87F4. Pharm: Induces substance P release (from dorsal root ganglia (DRG) neurons via PKC pathway). Ref: K. Nakae, et al, J. Antibiot., 2006, 59, 11 O

OH

HN H N

O

N

OH O

OH

O

N H

1097 6-epi-Avrainvillamide Type: Miscellaneous indole alkaloids. C26H29N3O4 Source: Mangrove-derived fungus Aspergillus taichungensis from mangrove Acrostichum aureum (root soil, no location given). Pharm: Cytotoxic (HL60, IC50 = 1.88 μmol/L; A549, IC50 = 1.92 μmol/L). Ref: S. Cai, et al, Org. Lett., 2013, 15, 2168 O

O

N

N H

O

N

+ –

O

1098 5-Chlorosclerotiamide Type: Miscellaneous indole alkaloids. C26H28ClN3O5 Source: Deep sea fungus Aspergillus westerdijkiae (sediment, S. China Sea), deep-sea fungus Aspergillus westerdijkiae DFFSCS013 (South China Sea). Pharm: Antifouling (Bugula neritina larval settlement, EC50 = 13.52 μg/mL, LC50 > 200 μg/mL, LC50/ EC50 > 14.8); cytotoxic (K562, IC50 = 44 μmol/L). Ref: J. Peng, et al, JNP, 2013, 76, 983│ X. Zhang, et al, J. Ind. Microbiol. Biotechnol., 2014, 41, 741

384

3 Pyrrole Indole and Imidazole Alkaloids

O

O

HO Cl

N N H

5

O

N H

O

H

1099 Costaclavine Type: Miscellaneous indole alkaloids. C16H20N2 Source: Marine-derived fungus Aspergillus fumigatus. Pharm: Cytotoxic (mouse leukemia cell line P388, weak). Ref: R. J. Cole, et al, J. Agric. Food Chem., 1977, 25, 826 8S

H

N

H 3 1

N H

1100 Cyanogramide Type: Miscellaneous indole alkaloids. C24H21N3O4 Source: Marine-derived actinomycete Actinoalloteichus cyanogriseus WH1-2216-6. Pharm: Cytotoxic (K562, IC50 = 12.9 μmol/L, MCF7, IC50 = 18.5 μmol/L,KB, IC50 = 16.8 μmol/L, MDR cell line K562/ A02, IC50 = 10.2 μmol/L, MDR cell line MCF7/Adr, IC50 = 36.0 μmol/L, MDR cell line KB/VCR, IC50 = 25.6 μmol/L, and could reverse multidrug resistance of K562/A02, MCF7/Adr and KB/VCR cells). Ref: P. Fu, et al, Org. Lett., 2014, 16, 3708 O

O N

N O

N O

1101 13-N-Demethyl-methylpendolmycin Type: Miscellaneous indole alkaloids. C22H31N3O2 Gray brown solid, [α]D25 = −45° (c = 0.33, MeOH). Source: Marine actinomycete Marinactinospora thermotolerans SCSIO 00652. Pharm: Antiplasmodial (Plasmodium falciparum lines 3D7 Drugsensitive line, IC50 = 20.75 μmol/L, control Chloroquine, IC50 = 0.0128 μmol/L; Dd2 Multi-drug-resistant line, IC50 = 18.67 μmol/L, Chloroquine, IC50 = 0.0974 μmol/L). Ref: H. Huang, et al, JNP, 2011, 74, 2122

3.16 Miscellaneous Indole Alkaloids

385

H S

H H N

OH

HN O N H

1102 2-(3,3-Dimethylprop-1-ene)-costaclavine Type: Miscellaneous indole alkaloids. C21H28N2 Source: Marine-derived fungus Aspergillus fumigatus. Pharm: Cytotoxic (mouse leukemia cell line P388, weak). Ref: R. J. Cole, et al, J. Agric. Food Chem., 1977, 25, 826 8R

H

N

H 3 1

N H

1103 2-(3,3-Dimethylprop-1-ene)-epi-costaclavine Type: Miscellaneous indole alkaloids. C21H28N2 Source: Marine-derived fungus Aspergillus fumigatus. Pharm: Cytotoxic (mouse leukemia cell line P388, weak). Ref: R. J. Cole, et al, J. Agric. Food Chem., 1977, 25, 826 8S

H

N

H 3 1

N H

1104 FumigaclavineB Type: Miscellaneous indole alkaloids. C16H20N2O mp 244–245 °C, mp 265–267 °C (double mp), [α]D = −6.3° (c = 1.2, MeOH). Source: Marine-derived fungus Aspergillus sydowi PFW1-13 (from driftwood sample, China). Pharm: Mycotoxin. Ref: M. Zhang, et al, JNP, 2008, 71, 985

386

3 Pyrrole Indole and Imidazole Alkaloids

N HO

H

H

N H

1105 Fumigaclavine C Type: Miscellaneous indole alkaloids. C23H30N2O2 Needles (MeOH), mp 194 °C. Source: Marine-derived fungus Aspergillus sydowi PFW1-13. Pharm: Cytotoxic (mouse leukemia cell line P388, weak); induces apoptosis (MCF7 breast cancer cells); mycotoxin. Ref: R. J. Cole, et al, J. Agric. Food Chem., 1977, 25, 826│ M. Zhang, et al, JNP, 2008, 71, 985│ Y. -X. Li, et al, Mar. Drugs, 2013, 11, 5063 N

O O

H

H

N H

1106 Hexaacetylcelenamide A Type: Miscellaneous indole alkaloids. C46H48BrN5O14 Source: Sponge Cliona celata (burrowing sponge). Pharm: Antimicrobial. Ref: R. J. Stonard, et al, JOC, 1980, 45, 3687│ U. Schmidt, et al, Angew. Chem., Int. Ed. Engl., 1984, 23, 991│ U. Schmidt, et al, Licbigs Ann. Chem., 1985, 785 O

O

O

O

O O

O

O O

H N

HN O

HN

O

O

O

O N H

N H

Br

1107 Hexaacetylcelenamide B Type: Miscellaneous indole alkaloids. C45H46BrN5O14 Source: Sponge Cliona celata (burrowing sponge). Pharm: Antimicrobial. Ref: R. J. Stonard, et al, JOC, 1980, 45, 3687

3.16 Miscellaneous Indole Alkaloids

387

O O O

O E/Z

O

O

O

O

HN O

O

O

H N

O

N H

O

HN

N H

O

Br

1108 N-Hydroxy-6-epi-stephacidin A Type: Miscellaneous indole alkaloids. C26H29N3O4 Source: Mangrove-derived fungus Aspergillus taichungensis from mangrove Acrostichum aureum (root soil, no location given). Pharm: Cytotoxic (HL60, IC50 = 4.45 μmol/L; A549, IC50 = 3.02 μmol/L). Ref: S. Cai, et al, Org. Lett., 2013, 15, 2168 O

O

N

N H

N

O

OH

1109 Isonotoamide B Type: Miscellaneous indole alkaloids. C26H29N3O4 Source: Marine-derived fungus Paecilomyces variotii EN-291 (endophytic). Pharm: Cytotoxic (NCI-H460, IC50 = 55.9 μmol/L). Ref: P. Zhang, et al, Chin. Chem. Lett., 2015, 26, 313 O O

N NH

H O

N H

O

1110 Mangrovamide C Type: Miscellaneous indole alkaloids. C27H33N3O3 Source: Mangrove-derived fungus Penicillium sp. (sediment, South China Sea). Pharm: AChE inhibitor (IC50 = 58.0 μmol/L). Ref: B. Yang, et al, Tetrahedron, 2014, 70, 3859

388

3 Pyrrole Indole and Imidazole Alkaloids

O N

HN

H N H

O O

1111 Methylpendolmycin-14-O-α-glucoside Type: Miscellaneous indole alkaloids. C29H43N3O7 Brown solid, [α]D25 = −67° (c = 0.12, CHCl3). Source: Marine actinomycete Marinactinospora thermotolerans SCSIO 00652. Pharm: Antiplasmodial (Plasmodium falciparum lines 3D7 Drug-sensitive line, IC50 = 10.43 μmol/L, control Chloroquine, IC50 = 0.0128 μmol/L; Dd2 Multi-drug-resistant line, IC50 = 5.03 μmol/L, Chloroquine, IC50 = 0.0974 μmol/L). Ref: H. Huang, et al, JNP, 2011, 74, 2122 OH H S

O

HO HO H H N

HO O

N O

N H

1112 Notoamide A Type: Miscellaneous indole alkaloids. C26H29N3O5 [α]D27 = −112° (c = 0.08, MeOH). Source: Marine-derived fungus Aspergillus sp. from mussel Mytilus edulis. Pharm: Cytotoxic ( HeLa and L1210, IC50 = 22–52 μg/mL). Ref: H. Kato, et al, Angew. Chem. Int. Ed. Engl., 2007, 46, 2254; 2013, 52, 7909 (corrigendum). O O

N

NH

H O

N

O

OH

1113 (–)-Notoamide B Type: Miscellaneous indole alkaloids. C26H29N3O4 [α]D27 = −118° (c = 0.06, MeOH). Source: Marine-derived fungus Aspergillus sp. from mussel Mytilus edulis. Pharm:

3.16 Miscellaneous Indole Alkaloids

389

Cytotoxic ( HeLa and L1210, IC50 = 22–52 μg/mL). Ref: H. Kato, et al, Angew. Chem. Int. Ed. Engl., 2007, 46, 2254; 2013, 52, 7909 (corrigendum). O O

N

NH S

S

H O

N

O

OH

1114 Notoamide I Type: Miscellaneous indole alkaloids. C26H27N3O4 [α]D29 = +31° (c = 0.1, MeOH/CHCl3). Source: Marine-derived fungus Aspergillus sp. MF 297-2 from mussel Mytilus edulis. Pharm: Cytotoxic (HeLa, IC50 = 21 μg/mL). Ref: S. Tsukamoto, et al, JNP,2008, 71, 2064│ S. Tsukamoto, et al, Org. Lett., 2009, 11, 1297│ S. Tsukamoto, et al, JNP, 2010, 73, 1438 O

O O 20

16

H N

21

N

O

N H

H

1115 Pentaacetylcelenamide C Type: Miscellaneous indole alkaloids. C44H46BrN5O12 Source: Sponge Cliona celata (Burrowing sponge). Pharm: Antimicrobial. Ref: R. J. Stonard, et al, Can. J. Chem., 1980, 58, 2121 O O O

O

O O O

H N

HN O HN O

O

O

O N H

N H

Br

1116 Pibocine A 2-Bromofestuclavin Type: Miscellaneous indole alkaloids. C16H19BrN2 mp 226–228 °C, [α]D = −36° (c = 0.14, EtOH). Source: Ascidian Eudistoma sp. (psychrophilic, cold water, Northern Sea of Japan). Pharm: Cytotoxic (EAC, ED50 = 12.5 μg/mL);

390

3 Pyrrole Indole and Imidazole Alkaloids

antimicrobial. Ref: T. N. Makarieva, et al, Tet. Lett., 1999, 40, 1591│ T. N. Makarieva, et al, JNP, 2001, 64, 1559│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) N

H

H Br N H

1117 Pibocine B Type: Miscellaneous indole alkaloids. C17H21BrN2O Thin cryst. (MeOH), mp > 358 °C, [α]D = −51° (c = 0.19, EtOH). Source: Ascidian Eudistoma sp. (psychrophilic, cold water, Northern Sea of Japan). Pharm: Antimicrobial; cytotoxic (mouse Ehrlich carcinoma cells). Ref: T. N. Makarieva, et al, Tet. Lett., 1999, 40, 1591│ T. N. Makarieva, et al, JNP, 2001, 64, 1559│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) N

H

H Br N O

1118 (–)-Sclerotiamide Type: Miscellaneous indole alkaloids. C26H29N3O5 mp 239–242 °C (dec), [α]D = −55.1° (c = 0.1, MeOH). Source: Marine-derived fungus Aspergillus sclerotiorum NRRL 5167, deep-sea fungus Aspergillus westerdijkiae DFFSCS013. Pharm: Insecticide (larvicide); antifeedant. Ref: A. C. Whyte, et al, JNP, 1996, 59, 1093│ J. Peng, et al, JNP, 2013, 76, 983 5

O

O

OH 11 10

N H

NH O

1

O

N 17

H

1119 Secobatzelline A Type: Miscellaneous indole alkaloids. C10H10ClN3O3 [α]D27 = −135° (c = 0.01, MeOH). Source: Sponge Batzella sp. (deep water, Caribbean). Pharm: Cytotoxic (P388, IC50 = 0.06 μg/mL, A549, IC50 = 0.04 μg/mL); inhibits calcineurin (CaN) (IC50 = 0.55 μg/mL); peptidase CPP32 inhibitor (IC50 = 0.02 μg/mL, significant as there are presently very few compound in the literature that demonstrate nmol/L

3.16 Miscellaneous Indole Alkaloids

391

potency for inhibition of either CaN or CPP32 activity). Ref: S. P. Gunasekera, et al, JNP, 1999, 62, 1208 HN

OH

O OH H 2N

NH Cl

1120 Secobatzelline B Type: Miscellaneous indole alkaloids. C10H9ClN2O4 [α]D24 = −18° (c = 0.01, MeOH). Source: Sponge Batzella sp. (deep water, Caribbean). Pharm: Cytotoxic (P388, IC50 = 1.22 μg/mL, A549, IC50 = 2.86 μg/mL); inhibits calcineurin (CaN) (IC50 = 2.21 μg/mL, significant as there are presently very few compound in the literature that demonstrate nmol/L potency for inhibition of either CaN or CPP32 activity). Ref: S. P. Gunasekera, et al, JNP, 1999, 62, 1208 HN

OH

O OH O

H 2N Cl

1121 Stephacidin A Type: Miscellaneous indole alkaloids. C26H29N3O3 Amorph. solid, [α]D = +6.15° (c = 0.26, CH2Cl2/MeOH). Source: Marine-derived fungus Aspergillus ochraceus WC 76466 (India waters). Pharm: Cytotoxic (PC3, IC50 = 2.10 μmol/L; LNCaP, IC50 = 1.00 μmol/L; A2780, IC50 = 4.00 μmol/L; A2780/DDP, IC50 = 6.80 μmol/L; A2780/Tax, IC50 = 3.60 μmol/L; HCT116, IC50 = 2.10 μmol/L; HCT116/mdr+, IC50 = 6.70 μmol/L; HCT116/topo, IC50 = 13.10 μmol/L; MCF7, IC50 = 4.20 μmol/L; SKBR3, IC50 = 2.15 μmol/ L; LX-1, IC50 = 4.22 μmol/L). Ref: J. F. Qian-Cutrone, et al, JACS, 2002, 124, 14556 O O 16

N H

20

H N

21

N

O

H

1122 Stephacidin B Type: Miscellaneous indole alkaloids. C52H54N6O8 Off-white amorph. solid. Source: Marine-derived fungus Aspergillus ochraceus WC76466 (India waters). Pharm: Cytotoxic (PC3, IC50 = 0.37 μmol/L; LNCaP, IC50 IC50 = 0.06 μmol/L; A2780, IC50 = 0.33 μmol/L; A2780/DDP, IC50 IC50 = 0.43 μmol/L; A2780/Tax, IC50 = 0.26 μmol/L; HCT116, IC50 = 0.46 μmol/L; HCT116/mdr+, IC50 = 0.46 μmol/L; HCT116/topo, IC50 =

392

3 Pyrrole Indole and Imidazole Alkaloids

0.42 μmol/L; MCF7, IC50 = 0.27 μmol/L; SKBR3, IC50 = 0.32 μmol/L; LX-1, IC50 IC50 = 0.38 μmol/L). Ref: J. F. Qian-Cutrone, et al, JACS, 2002, 124, 14556 OH

H

N

O

N O O

O

H

N

H N

O

O

N

N

+ –

H

O

1123 Surugatoxin Type: Miscellaneous indole alkaloids. C25H26BrN5O13 Prisms + 7 H2O, mp 300 °C. Source: Prosobranch (Japanese ivory shell) Babylonia japonica (midgut gland, Suruga, Japan). Pharm: Toxic; LD50 (mus, ip) = 0.45 μg/kg. Ref: T. Kosuge, et al, Tet. Lett., 1972, 2545│ S. Inoue, et al, Tet. Lett., 1984, 25, 4407│ T.Kosuge, et al, CPB, 1985, 33, 2890│ S. Inoue, et al, Tetrahedron, 1994, 50, 2729│ S. Inoue, et al, Tetrahedron, 1994, 50, 2753 OH HO

OH

HO

O HO

OH O

H N

H N

NH

N OH

H

O Br

N H

O

O

O

3.17 Imidazole Alkaloids 1124 Aminozooanemonin Type: Imidazole alkaloids. C7H11N3O2 Amorph. solid. Source: Sponge Agelas dispar (Bahamas). Pharm: Antibacterial (gram-positive bacteria, Bacillus subtilis, MIC = 2.5 μg/mL, Staphylococcus aureus, MIC = 8.5 μg/mL). Ref: F. Cafieri, et al, JNP, 1998, 61, 1171

N

OH O

N

NH

3.17 Imidazole Alkaloids

393

1125 Anatoxin a (S) Type: Imidazole alkaloids. C7H17N4O4P −20 °C slowly dec. Source: Cyanobacterium Anabaena flos-aquae NRC525.17. Pharm: Neurotoxin (potent, anticholinesterase activity); LD50 (mus, ipr) = 0.05 mg/kg. Ref: S. Matsunaga, et al, JACS, 1989, 111, 8021

N S HN

N

O

O P

NH

HO O

1126 Bromodeoxytopsentin 21-Bromotopsentin A Type: Imidazole alkaloids. C20H13BrN4O Amorph. yellow solid, mp 240–243 °C. Source: Sponge Spongosorites genitrix (Korea Waters). Pharm: Cytotoxic (K562, LC50 = 0.6 μg/mL). Ref: J. Shin, et al, JNP, 1999, 62, 647 N Br

O

N H N H

N H

1127 5-BromoVerongamine Type: Imidazole alkaloids. C15H17BrN4O3 Oil. Source: Sponges Pseudoceratina sp. (Curacao), and Verongula gigantea (deep water, Bahamas). Pharm: Inhibits settlement of barnacle larvae (EC50 = 1.03 mg/mL); histamine-H3 antagonist. Ref: R. Mierzwa, et al, JNP, 1994, 57, 175│ H. H. Wassermann, et al, JOC, 1998, 63, 5581│ I. Thirionet, et al, Nat. Prod. Lett., 1998, 12, 209 O Br H N

O

HO

N

N H

N

1128 12-Chloro-11-hydroxydibromoisophakellin Type: Imidazole alkaloids. C11H10Br2ClN5O2 [α]D23 = +51.0° (c = 0.408, MeOH). Source: Sponge Axinella brevistyla. Pharm: Antifungal (yeast Saccharomyces cerevisiae, 30 μg/disk), cytotoxic (L1210, IC50 = 2.5 μg/mL). Ref: S. Tsukamoto, et al, JNP. 2001, 64, 1576

394

3 Pyrrole Indole and Imidazole Alkaloids

Br

Br H N

NH

H 2N N

N

O

HO Cl

1129 Clathridine A Type: Imidazole alkaloids. C16H15N5O4 Cryst. (CHCl3), mp 260–262 °C (dec). Source: Calcareous sponge Clathrina clathrus, nudibranch Notodoris gardineri (Great Barrier Reef and Fiji). Pharm: Antimicrobial. Ref: P. Siminiello, et al, Tetrahedron, 1989, 45, 3873│ A. R. Carroll, et al, Aust. J. Chem., 1993, 48, 1229│ K. A. Alvi, et al, Tetrahedron, 1993, 49, 329

O

N

O

N

H N

O N

N O

1130 Clathridine C Type: Imidazole alkaloids. C15H15N5O3 Yellow plates (DMSO), mp 255–257 °C. Source: Calcareous sponge Leucetta sp. (Great Barrier Reef). Pharm: Cytotoxic (weak). Ref: J. C. Boehm, et al, JMC, 1993, 36, 3333│ R. Carroll, et al, Aust. J. Chem., 1993, 48, 1229

N

H N O

N N

N

O OH

1131 Dorimidazole A Type: Imidazole alkaloids. C11H13N3O Yellow powder; cryst. (MeCN) (hydrobromide), mp 175–176 °C (hydrobromide). Source: Nudibranches Notodoris gardineri (IndoPacific Sea) and Notodoris citrina. Pharm: Anthelminthic, antiparasitic. Ref: K. A. Alvi, et al, JNP, 1991,54, 1509│ K. A. Alvi, et al, Tetrahedron, 1993, 49, 329│ P. Molina, et al, JOC, 1999, 64, 2540

3.17 Imidazole Alkaloids

395

N NH2 N

HO

1132 Dysideanin A Type: Imidazole alkaloids. C8H14N3O2S1+ Source: Sponge Dysidea sp. (Lingshui County, Hainan, China). Pharm: Antibacterial (weak). Ref: S. Ren, et al, J. Antibiot., 2010, 63, 699

H N N

S O

+

O NH2

1133 Echinobetaine B Type: Imidazole alkaloids. C8H12N2O3 [α]D = +30° (c = 0.6, MeOH) (TFA salt). Source: Sponge Echinodictyum sp. Pharm: Nematocide. Ref: R. J. Capon, et al, Org. Biomol. Chem., 2005, 3, 118 O –

O

N

+

O N

1134 Girolline Giracodazole Type: Imidazole alkaloids. C6H11ClN4O Powder (hydrochloride), [α]D20 = +7.9° (c = 0.84, MeOH). Source: Sponges Axinella brevistyla and Cymbastela cantharella [Syn. Pseudaxinyssa cantharella]. Pharm: Cytotoxic (in vitro); antineoplastic (in vivo); protein biosynthesis inhibitor. Ref: A. Ahond, et al, C. R. Acad. Sci. Paris, (série 2), 1988, 307, 145│ A. Ahond, et al, Tetrahedron, 1992, 48, 4327│ A. A. Mourabit, et al, JNP, 1997, 60, 290│ R. B. Kinnel, et al, JOC, 1998, 63, 3281│ S. Marchais, et al, Tet. Lett., 1998, 39, 8085│ S. Tsukamoto, et al, JNP. 2001, 64, 1576 N

Cl

NH2

H 2N

N H OH

396

3 Pyrrole Indole and Imidazole Alkaloids

1135 2-(4-Hydroxybenzoyl)-4(5)-(4-hydroxyphenyl)-1H-imidazole Type: Imidazole alkaloids. C16H12N2O3 Amorph. yellow solid, [α]D25 = 0° (c = 0.08, MeOH). Source: Ascidian Botryllus leachi (Spain). Pharm: Cytotoxic (A549, MEL28, HT29, ED50 = 5 μg/mL). Ref: R. Durán, et al, Tetrahedron, 1999, 55. 13225 H N

O

N

HO

OH

1136 Isonaamidine C Type: Imidazole alkaloids. C23H23N3O3 Amorph. yellow solid. Source: Calcareous sponge Leucetta sp., nudibranch Notodoris gardineri. Pharm: Cytotoxic (HM02, GI50 = 5.3 μg/mL; HepG2, GI50 = 2.2 μg/mL; Huh7, GI50 = 2.1 μg/mL). Ref: K. A. Alvi, et al, Tetrahedron, 1993, 49, 329│ B. R. Copp, et al, JMC, 1998, 41, 3909│ H. Gross, et al, JNP, 2002, 65, 1190

O

N H 2N

O

N

O

1137 Isonaamidine D Type: Imidazole alkaloids. C21H19N5O4 Amorph. yellow solid. Source: Calcareous sponge Leucetta cf. chagosensis. Pharm: Antifungal (Aspergillus niger, MIC = 100 μg/mL). Ref: S. Carmely, et al, Tetrahedron, 1989, 45, 2193│ X. Fu, et al, JNP, 1998, 61,384 N O

N

OH

NH O N

NH O

1138 Isonaamidine E Type: Imidazole alkaloids. C24H25N5O5 Amorph. yellow solid. Source: Calcareous sponge Leucetta chagosensis. Pharm: Cytotoxic (HM02, GI50 = 7.0 μg/mL; HepG2, GI50 = 7.0 μg/mL; Huh7, GI50 = 1.3 μg/mL). Ref: H. Gross, et al, JNP, 2002, 65, 1190

3.17 Imidazole Alkaloids

O

N

O

397

O

N N

N H

O

N

O

1139 Kealiinine A Type: Imidazole alkaloids. C20H19N3O3 Yellow-brown powder. Source: Calcareous sponge Leucetta chagosensis. Pharm: Toxic (brine shrimp). Ref: W. Hassan, et al, JNP, 2004, 67, 817 O

H

5

HO

N NH N

O

1140 Leucettamidine Type: Imidazole alkaloids. C25H24N6O5 Source: Calcareous sponge Leucetta microraphis (Palau, Oceania). Pharm: Leukotriene B4 receptor binding activity (IC50 = 15.6 μmol/L, Ki = 5.3 μmol/L, significant, leukotriene B4 receptor antagonist). Ref: G. W. Chan, et al, JNP, 1993, 56, 116│ J. C. Boehm, et al, JMC, 1993, 36, 3333

N N O

N

O

N

O

N

HN O O

1141 Leucettamine A Type: Imidazole alkaloids. C20H19N3O4 Yellowish amorph. solid. Source: Calcareous sponge Leucetta microraphis (Palau, Oceania). Pharm: Leukotriene B4 receptor binding activity (IC50 = 4.0 μmol/L, Ki = 1.3 μmol/L, potent, as leukotriene B4 receptor antagonist, Leucettamine A is a new structure lead to inflammation therapy); leukotriene B4 receptor binding activity (hmn whole U937 cell receptor binding assay, high affinity, IC50 = 0.75 μmol/L). Ref: G. W. Chan, et al, JNP, 1993, 56, 116│ J. C. Boehm, et al, JMC, 1993, 36, 3333

398

3 Pyrrole Indole and Imidazole Alkaloids

N NH2 N

O O

O O

1142 Leucettamine B Type: Imidazole alkaloids. C12H11N3O3 Cream solid. Source: Calcareous sponge Leucetta microraphis. Pharm: Antifungal; anti-AD preclinical trial (Target: CDC2like kinase inhibitors, CLK1, Dyrk1A and Dyrk2 inhibition and CLK3 moderate inhibition. Model: Hmn U937 cell membrane) (Russo, 2016). Ref: G, W. Chan, et al, JNP, 1993, 56, 116│ J. C. Boehm, et al, JMC, 1993, 36, 3333│ P. Molina, et al, Tet. Lett., 1994, 35, 2235│ P. Russo, et al, Mar. Drugs, 2016, 14, 5 (review)

O

O O

N

N NH2

1143 Lipopurealin A Type: Imidazole alkaloids. C31H48Br2N6O4 Amorph. solid (hydrochloride), mp 94–95 °C (hydrochloride). Source: Sponge Psammaplysilla purea (Okinawa). Pharm: Na/KATPase inhibitor. Ref: H. Wu, et al, Experientia, 1986, 42, 855 Br O H N 12

O

OH N

H N

Br O

N

NH NH2

1144 Lipopurealin B Type: Imidazole alkaloids. C32H50Br2N6O4 Amorph. solid (hydrochloride), mp 93–95 °C (hydrochloride). Source: Sponge Psammaplysilla purea (Okinawa). Pharm: Na/KATPase inhibitor. Ref: H. Wu, et al, Experientia, 1986, 42, 855

3.17 Imidazole Alkaloids

Br

OH

O H N

N

H N

Br

11

399

N

O

O

NH NH2

1145 Lipopurealin C Type: Imidazole alkaloids. C33H52Br2N6O4 Amorph. solid (hydrochloride), mp 108– 110 °C (hydrochloride). Source: Sponge Psammaplysilla purea (Okinawa). Pharm: Na/K-ATPase inhibitor. Ref: H. Wu, et al, Experientia, 1986, 42, 855 Br

OH

O N

H N 14

H N

Br

N

O

O

NH NH2

1146 Malonganenone B Type: Imidazole alkaloids. C27H42N4O3 Colorless glass. Source: Gorgonians Leptogorgia gilchristi (near Ponto Malongane, Mozambique), Euplexaura robusta (Weizhou I., Guangxi, China) and Euplexaura nuttingi (Pemba I., Tanzania). Pharm: Cytotoxic (anti-oesophageal cancers: WHCO1, IC50 = 25.1 μmol/L; WHCO5, IC50 > 100.0 μmol/L; WHCO6, IC50 = 50.7 μmol/L; KYSE70, IC50 = 26.9 μmol/L; KYSE180, IC50 = 24.6 μmol/L; KYSE520, IC50 = 18.9 μmol/L; MCF12, IC50 = 18.7 μmol/L); cytotoxic (HeLa, IC50 > 100 μmol/L, control Adriamycin, IC50 = (0.38 ± 0.05)μmol/L; K562, IC50 > 100 μmol/L, Adriamycin, IC50 = (0.23 ± 0.02)μmol/L) (Zhang, 2012). Ref: R. A. Keyzers, et al, Tetrahedron, 2006, 62, 2200│ H. Sorek, et al, JNP, 2007, 70, 1104│ J. -R. Zhang, et al, Chem. Biodiversity, 2012, 9, 2218 O N N

O N

N H 11'

O

1147 Malonganenone F Type: Imidazole alkaloids. C27H42N4O3 Colorless oil. Source: Gorgonians Euplexaura nuttingi (Pemba I., Tanzania) and Euplexaura robusta (Weizhou I., Guangxi, China). Pharm: Cytotoxic (inhibits growth of K562 and UT7); induces apoptosis (transformed

400

3 Pyrrole Indole and Imidazole Alkaloids

mammalian, 1.25 μg/mL); cytotoxic (HeLa, IC50 > 100 μmol/L, control Adriamycin, IC50 = (0.38 ± 0.05)μmol/L; K562, IC50 > 100 μmol/L, Adriamycin, IC50 = (0.23 ± 0.02) μmol/L) (Zhang, 2012). Ref: H. Sorek, et al, JNP, 2007, 70, 1104│ J. -R. Zhang, et al, Chem. Biodiversity, 2012, 9, 2218 HN O

O 1

7

N

6 5 3

N

4

1'

7'

3'

13'

11'

N 9

2

O

H

1148 Malonganenone G Type: Imidazole alkaloids. C27H42N4O3 Colorless oil. Source: Gorgonians Euplexaura nuttingi (Pemba I., Tanzania) and Euplexaura robusta (Weizhou I., Guangxi, China). Pharm: Cytotoxic (inhibits growth of K562 and UT7); induces apoptosis (transformed mammalian, 1.25 μg/mL); cytotoxic (HeLa, IC50 > 100 μmol/L, control Adriamycin, IC50 = (0.38 ± 0.05)μmol/L; K562, IC50 > 100 μmol/L, Adriamycin, IC50 = (0.23 ± 0.02)μmol/L) (Zhang, 2012). Ref: H. Sorek, et al, JNP, 2007, 70, 1104│ J. -R. Zhang, et al, Chem. Biodiversity, 2012, 9, 2218 HN O

O 1

7

N

6 5 3

N

4

7'

3'

11'

13'

N 9

2

O

1'

H

1149 Naamidine A Type: Imidazole alkaloids. C23H13N5O4 Yellow foaming oil. Source: Calcareous sponge Leucetta chagosensis (Red Sea), nudibranch Notodoris citrina. Pharm: Antagonist of epidermal growth factor receptor. Ref: S. armely, et al, Tetrahedron, 1989, 45, 2193│ I. ancini, et al, Helv. Chim. Acta, 1995, 78, 1178│ B. R. Copp, et al, JMC, 1998, 41, 3909

N

N HO

O N N

N O

O

3.17 Imidazole Alkaloids

401

1150 Naamidine F Type: Imidazole alkaloids. C25H25N5O7 Yellow needles, mp 172–174 °C. Source: Calcareous sponge Leucetta sp. (Great Barrier Reef). Pharm: Cytotoxic (weak). Ref: J. C. Boehm, et al, JMC, 1993, 36, 3333 O O

N

O

N

H N N

O

O N

O O

1151 Phorbatopsin A Type: Imidazole alkaloids. C10H9N3O2 Source: Sponge Phorbas topsenti (Marseille, France). Pharm: Antioxidant. Ref: T. D. Nguyen, et al, Tetrahedron, 2012, 68, 9256 NH2 HN

N

HO

O

1152 Phorbatopsin B Type: Imidazole alkaloids. C10H11N3O3 Source: Sponge Phorbas topsenti (Marseille, France). Pharm: Antioxidant. Ref: T. D. Nguyen, et al, Tetrahedron, 2012, 68, 9256 NH2 HN HO

N O

OH

1153 Phorbatopsin C Type: Imidazole alkaloids. C10H11N3O2 Source: Sponge Phorbas topsenti (Marseille, France). Pharm: Antioxidant. Ref: T. D. Nguyen, et al, Tetrahedron, 2012, 68, 9256 NH2 HN HO

N O

402

3 Pyrrole Indole and Imidazole Alkaloids

1154 Purealidin A Type: Imidazole alkaloids. C17H22Br2N6O3 Amorph. solid. Source: Sponges Psammaplysilla purea and Pseudoceratina verrucosa. Pharm: Cytotoxic (L1210, IC50 = 1.1 μg/mL); NaK-ATPase inhibitor (0.0001 mol/L, InRt = 22%, weak); ichthyotoxic. Ref: M. Ishibashi,et al, Experientia, 1991, 47, 299 H 2N

Br O

N

OH H N

Br

N N H

O

NH2

1155 Purealidin D Type: Imidazole alkaloids. C22H25Br2N6O31+ Source: Sponge Psammaplysilla purea (Okinawa). Pharm: Na/K-ATPase inhibitor. Ref: M. Tsuda, et al, Tet. Lett., 1992, 33, 2597│ M. Tsuda, et al, JNP, 1992, 55, 1325 Br N

+

OH

O

N

H N

Br

N NH2

O

N H

1156 Purealidin E Type: Imidazole alkaloids. C20H29Br2N6O31+ Amorph. solid (bis(trifluoroacetate)). Source: Sponge Psammaplysilla purea (Okinawa). Pharm: Na/K-ATPase inhibitor. Ref: M. Tsuda, et al, Tet. Lett., 1992, 33, 2597│ M. Tsuda, et al, JNP, 1992, 55, 1325 Br N

+

O

OH N

H N

Br O

N NH2 N H

1157 Purealidin M Type: Imidazole alkaloids. C15H17Br2N5O4 Oil (trifluoroacetate). Source: Sponge Psammaplysilla purea (Okinawa). Pharm: Cytotoxic (L1210, IC50 > 10 μg/mL; KB, IC50 > 10 μg/mL). Ref: J. Kobayashi, et al, CPB, 1995, 43, 403

3.17 Imidazole Alkaloids

403

Br HO

O

N

H N

N

Br

NH2

O

OH

N H

1158 Purealidin N Type: Imidazole alkaloids. C15H16Br2N4O4 Oil. Source: Sponge Psammaplysilla purea (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 0.07 μg/mL, KB, IC50 = 0.074 μg/mL). Ref: J. Kobayashi, et al, CPB, 1995, 43, 403│ T. R. Boehlow, et al, JOC, 2001, 66, 3111 Br HO

O

N

H N

Br

N

O

OH

N H

1159 Pyronaamidine 9-N-methylimine Type: Imidazole alkaloids. C26H30N6O5 Yellow crystals, (CH2Cl2/MeOH), mp 222–225 °C. Source: Calcareous sponge Leucetta cf. chagosensis (Rota, Northern Mariana Is., Pacific Ocean). Pharm: Cytotoxic (A549, GI50 = 6 μg/mL; MCF7, GI50 = 3 μg/mL; HT29, GI50 = 6 μg/mL). Ref: A. Plubrukarn, et al, JNP, 1997, 60, 712 OH O

N

O

N

OH

N N

N N

O

1160 Stellettazole D Type: Imidazole alkaloids. C22H37N4O1+ [α]D25 = +6.1° (c = 0.10, MeOH). Source: Sponge Jaspis duoaster (Cape Sada, Ehime Prefecture, Japan). Pharm: Cytotoxic (P388, IC50 = 29.1 μg/mL; HeLa, IC50 = 83.6 μg/mL). Ref: S. Sato, et al, Chem. Lett., 2011, 40, 186

404

3 Pyrrole Indole and Imidazole Alkaloids

H +

H

N

H

H N N O

N

1161 Ulosantoin Type: Imidazole alkaloids. C5H9N2O5P Cryst. (Me2CO/isooctane), mp 127–128 °C. Source: Sponge Ulosa ruetzleri (Bermuda). Pharm: Insecticide. Ref: B. C. VanWagenen, et al, JOC, 1993, 58, 335 O N

O N

O

P

O

O

+

H

1162 Zorrimidazolone Type: Imidazole alkaloids. C11H13N3O4 Pink amorph. powder. Source: Ascidian Polyandrocarpa zorritensis (Bay of Taranto, Mediterranean Sea). Pharm: Cytotoxic (C6, IC50 = (155 ± 13)μmol/L; HeLa and H9c2, inactive). Ref: A. Aiello, et al, Mar. Drugs, 2011, 9, 1157 O O HO

N

HO N

NH 2

Index 1 Compound Name and Synonym Index This index lists in alphabetical order all active compound’s 1,256 entry names including both 1,162 key names and 94 synonym names contained in the bodies of compound entries. A equal sign ( = ) and compound code number (from 1 to 1,162) follow the name immediately for locating the compound in the “Handbook of Active Marine Natural Products Volume 3” book. Following symbols are ineffective in ordering: D-, L-, dl, R-, S-, E-, Z-, O-, N-, C-, H-, cis-, trans-, ent-, epi-, meso-, erythro-, threo-, sec-, seco-§, m-, o-, p-, n-, α-, β-, γ-, δ-, ε-, κ-, ξ-, ψ-, ω-, (+), (−), (±) etc., and: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, {, }, [,], (,), ,, ;, , *, ‘, ‘‘, ‘‘‘, →, etc. (§ note: In the books regular “seco-” is effective in ordering as “nor-”.) A Aburatubolactam A = 579. Aburatubolactam B = 580. Aburatubolactam C = 581. Acantholactam = 892. Acanthomanzamine A = 893. Acanthomanzamine B = 894. Acanthomanzamine D = 895. Acanthomanzamine E = 896. Acarnidine C = 6. 2-[(2-Acetamidopropanoyl)amino]benzamide = 124. N-(1-Acetoxymethyl-2-methoxyethyl)-7-methoxy4-eicosenamide = 125. N-{1-[4-(Acetylamino)phenyl]-3-hydroxy-1(1H-indol-3-yl)propan-2-yl}-2,2dichloroacetamide = 669. 14-O-(N-Acetylglucosaminyl) teleocidin A = 1096. N-Acetyltyramine = 218. Ageladine A = 445. Agelanesin A = 335. Agelanesin B = 336. Agelanesin C = 337. Agelanesin D = 338. (–)-Agelastatin A = 446. Agelastatin C = 447. Agelastatin D = 448. Ageliferin = 449. Agelorin A = 238. Agelorin B = 239. Alteramide A = 582. Alternatamide A = 940. Alternatamide B = 941. Alternatamide C = 942. Alternatamide D = 943. Amathamide C = 540.

https://doi.org/10.1515/9783110655193-004

Amathamide H = 541. Amathaspiramide A = 542. Amathaspiramide E = 543. Ambiguine H isonitrile = 1044. Ambiguine I isonitrile = 1045. 4-(2-Aminoethyl)-2-bromophenol = 219. Aminoethylsulfonic acid = 4. o-Aminophenol = 210. 3-Amino-1-propanesulfonic acid = 3. Aminozooanemonin = 1124. Anatoxin a (S) = 1125. Ancorinoside A = 583. Ancorinoside B = 584. Ancorinoside C = 585. Ancorinoside D = 586. Andrimide = 619. Antibiotic B 5354A = 211. Antibiotic B 5354B = 216. Antibiotic B 5354C = 217. Antibiotic BE 18591 = 413. Antibiotic JBIR 03 = 1059. Antibiotic M 146791 = 629. Antibiotic NI 15501A = 124. Antibiotic NP 25302 = 626. Antibiotic PF 1126A = 177. Antibiotic PF 1126B = 178. Antibiotic ZHD-0501 = 789. Antipathine A = 778. Aplaminal = 183. Aplaminone = 220. Aplicyanin B = 55. Aplicyanin D = 56. Aplicyanin E = 57. Aplicyanin F = 58. Aplysamine 2 = 240. Aplysamine 3 = 241. Aplysamine 4 = 242.

406

Index 1 Compound Name and Synonym Index

Aplysamine 5 = 243. Aplysamine 6 = 221. Aplysamine 7 = 244. Aplysinopsin = 1008. Aplysioviolin = 521. Arborescidine D = 808. Arcyriaflavin A = 790. Arsindoline B = 724. Arundine = 761. Asperazine = 988. Aspochalasin A = 634. Aspochalasin D = 635. Aspochalasin H = 636. Aspochalasin I = 637. Aspochalasin J = 638. Aurantoside A = 587. Aurantoside B = 588. Aurantoside C = 589. Aurantoside D = 590. Aurantoside E = 591. Aurantoside F = 592. Aurantoside K = 593. 6-epi-Avrainvillamide = 1097. Axidjiferoside A = 126. Axidjiferoside B = 127. Axidjiferoside C = 128. Axinellamine A = 450. Axinellamine B = 451. Axinellamine C = 452. (Z)-Axinohydantoin = 453. B Barmumycin = 544. Bastadin 1 = 245. Bastadin 2 = 246. Bastadin 3 = 247. Bastadin 4 = 248. Bastadin 5 = 249. Bastadin 6 = 250. Bastadin 7 = 251. Bastadin 8 = 252. Bastadin 9‡ = 253. Bastadin 10 = 254. Bastadin 11 = 255. Bastadin 12 = 256. Bastadin 13 = 257. Bastadin 14 = 258. Bastadin 15 = 259. Bastadin 16 = 260.

(E,E)-Bastadin 19 = 261. Bastadin 20 = 262. Bastadin 21 = 263. Bastadin 22 = 264. Bastadin 24 = 265. Bastadin 25 = 266. Bastadin 26 = 267. Batzelladine A = 75. Batzelladine B = 76. Batzelladine D = 77. Batzelladine E = 78. Batzelladine F = 79. Batzelladine L = 80. Batzelladine M = 81. BDS 391 = 1010. Bengamide A = 184. Bengamide B = 185. Bengamide C = 186. Bengamide D = 187. Bengamide E = 188. Bengamide F = 189. Bengamide G = 190. Bengamide M = 191. Bengamide N = 192. Bengamide O = 193. Bengamide P = 194. Bengamide Q = 195. Bengamide Y = 196. Bengamide Z = 197. Biliverdin = 522. Biliverdin IXα = 522. Bisaprasin = 268. 3,3′-Bis(4,6-dibromo-2-methylsulfinyl)indole = 725. 7,7-Bis(3-indolyl)-p-cresol = 726. 2,2-Bis(3-indolyl)indoxyl = 737. 3,3′-Bis(2′-methylsulfinyl-2-methylthio4,6,4′,6′-tetrabromo)indole = 727. Bispsammaplin A = 269. Bisucaberin = 198. Bohemamine = 624. Bonellin = 523. Botryllamide D = 270. Botryllamide G = 271. Brevicompanine A = 989. Brevicompanine B = 990. Brevicompanine C = 991. Brevicompanine E = 992. Brevicompanine H = 993.

Index 1 Compound Name and Synonym Index

Brocaeloid C = 809. 2-Bromoageliferin = 454. 7-Bromo-1-(6-bromo-1H-indol-3-yl)-9Hcarbazole = 779. 7-Bromocavernicolenone = 199. Bromochelonin B = 944. Bromodeoxytopsentin = 1126. 6-BromodidemnimideA = 1014. 6-Bromo-4,5-dihydroxyindole = 670. 6-Bromo-4,7-dihydroxyindole = 671. (−)-5-Bromo-N,N-dimethyltryptophan = 945. 6-Bromo-1′-ethoxy-1′,8-dihydroaplysinopsin = 1009. 3-Bromofascaplysin = 810. 2-Bromofestuclavin = 1116. 3-Bromohomofascaplysin A = 811. 6-Bromo-1′-hydroxy-1′,8-dihydroaplysinopsin = 946. 6-Bromo-5-hydroxy-1H-indole = 672. 3-Bromo-5-hydroxy-4-methoxybenzamide = 129. 2-(3-Bromo-5-hydroxy-4-methoxyphenyl) acetamide = 130. (Z)-3-Bromohymenialdisine = 455. (E)-3-Bromohymenialdisine = 513. (+)-5-Bromohypaphorine = 947. 6-Bromoindole-3-carbaldehyde = 673. 6-Bromo-1H-indole-3-carboxylic acid methyl ester = 674. 6-Bromo-1′-methoxy-1′,8-dihydroaplysinopsin = 948. 6-Bromo-Nb-methyl-Na-prenyltryptamine = 949. 4-Bromopalauamine = 456. 6-Bromopenitrem B = 1060. Bromopsammaplin A = 272. 3-Bromo-1H-pyrrole-2,5-dione = 339. 3-Bromostyloguanidine = 457. Bromotopsentin = 777. 6-Bromotopsentin A = 1023. 21-Bromotopsentin A = 1126. (+)-7-Bromotrypargine = 59. 5-BromoVerongamine = 1127. Bunodosine 391 = 1010. C Calcareous sponge Leucetta Acetylenic Alkaloid = 1. Caprolactin A = 200.

Caprolactin B = 201. N-Carboxamido-staurosporine = 791. Carteramine A = 458. Cathestatin A = 177. Cathestatin B = 178. Cathestatin C = 7. Caulerchlorin = 728. Caulerpin = 729. Celenamide E = 179. Celeromycalin = 82. Cephalimysin A = 202. Cephalimysin C = 203. Cephalimysin D = 204. Ceratamine A = 205. Ceratinamine = 273. Ceratinine A = 321. Ceratinine B = 322. Ceratinine D = 323. Chaetoglobosin A = 639. Chelonin B = 950. Chlorizidine A = 625. Chloro-bisindole = 730. 12-Chloro-11-hydroxydibromoisophakellin = 1128. 12-Chloro-11-hydroxyldibromoisophakellin = 459. 3-Chloro-1H-indole = 675. Chlorophyllone a = 524. 5-Chlorosclerotiamide = 1098. Chloroxiamycin = 780. Chondriamide A = 731. Chondriamide B = 732. Chondriamide C = 733. Circumdatin C = 171. Circumdatin F = 172. Circumdatin G = 173. Circumdatin I = 174. Citorellamine = 734. Cladosin C = 594. Cladosin Cmajor = 595. Cladosin Cminor = 596. Cladosin F = 597. Cladosin G = 598. Clathramide A = 460. Clathramide B = 461. Clathramide C = 462. Clathramide D = 463. Clathriadic acid = 83. Clathridine A = 1129.

407

408

Index 1 Compound Name and Synonym Index

Clathridine C = 1130. Clathrodine = 464. Clionamide = 951. Complanine = 131. Conicamine = 952. Conioimide = 1086. Convalutamydine A = 676. Convolutamide A = 545. Convolutamide B = 546. Convolutamide D = 547. Convolutamide E = 548. Convolutamide F = 549. Convolutamine A = 222. Convolutamine B = 223. Convolutamine C = 224. Convolutamine D = 324. Convolutamine E = 325. Convolutamine F = 225. Convolutamine I = 8. Convolutamydine B = 677. Convolutamydine C = 678. Convolutamydine D = 679. Coproverdine = 781. Corallistin A = 525. Costaclavine = 1099. Crambescidin 800 = 84. Crambescidin 816 = 9. Crambescidin 826 = 85. Crambescidin 830 = 86. Crambescidin 844 = 87. Cyanogramide = 1100. 5-(19-Cyanononadecyl)-1H-pyrrole2-carboxaldehyde = 340. 5-(23-Cyano-16-tricosenyl)-1H-pyrrole2-carboxaldehyde = 383. Cyclizidine = 629. Cycloaplysinopsin C = 465. Cyclobastadin 1 = 248. Cyclobastadin 2 = 249. Cyclobastadin 2 = 250. Cyclobastadin 4 = 251. Cyclobispsammaplin A = 274. α-Cyclopiazonic acid = 1046. 5-epi-α-Cyclopiazonic acid. = 1057. Cycloprodigiosin hydrochloride = 526. Cylindramide = 599. Cypridina Luciferin = 60. Cytochalasin B2 = 640. Cytochalasin E = 641.

Cytochalasin K = 642. Cytochalasin Q = 643. Cytochalasin Z7 = 644. Cytochalasin Z8 = 645. Cytochalasin Z9 = 646. Cytochalasin Z11 = 647. Cytochalasin Z12 = 648. Cytochalasin Z16 = 649. Cytochalasin Z17 = 650. Cytochalasin Z18 = 651. Cytochalasin Z19 = 652. Cytoglobosin C = 653. Cytoglobosin D = 654. D Damipipecoline = 341. Damituricine = 342. 16-Debromoaplysamine 4 = 275. (Z)-Debromoaxinohydantoin = 466. 2-Debromodispacamide A = 479. (10Z)-Debromohymenialdisine = 467. Debromooxysceptrine = 468. Debromosceptrine = 469. Deepoxybohemamine = 626. Deformylflustrabromine = 953. Deformylflustrabromine B = 954. Dehydroxypaxilline = 1061. 13-N-Demethyl-methylpendolmycin = 1101. 4a-Demethylpaspaline-4a-carboxylic acid = 1062. 4a-Demethylpaspaline-3,4,4a-triol = 1063. N13-Demethylteleocidin A1 = 1038. Dendridine A = 735. Deoxaphomin C = 655. 3-Deoxo-4b-deoxypaxilline = 1064. 13-Deoxycrambescidin 816 = 84. 18-Deoxycytochalasin Q = 656. 7-Deoxycytochalasin Z7 = 657. 11-Deoxyfistularin 3 = 276. N-(6-Deoxy-β-D-gulopyranosyl)-tjipanazole D = 806. 6-Deoxymanzamine X = 897. 1-Deoxysecofascaplysin A = 812. 11-Deoxytetrodotoxin = 106. 3ʹ-Deoxytubastrine = 61. 2,6-Dibromo-4-acetamido4-hydroxycyclohexadienone = 132. Dibromoagelaspongin = 470. 2,2′-Dibromoageliferin = 471.

Index 1 Compound Name and Synonym Index

(8E)-5,6-Dibromo-2′-N-demethyl-aplysinopsin = 1011. (8Z)-5,6-Dibromo-2′-N-demethyl-aplysinopsin = 1012. 4- (2,3-Dibromo-4,5-dihydroxybenzylamino)4-oxobutanoic acid = 133. 3-(2,3-Dibromo-4,5-dihydroxybenzyl) pyrrolidine-2,5-dione = 620. 5,6-Dibromo-L-hypaphorine = 955. 3,6-Dibromo-1H-indole = 680. 3,4-Dibromomaleimide = 343. 4,5-Dibromo-N2-methoxymethyl-1H-pyrrole2-carboxamide = 134. 4,5-Dibromopalauamine = 472. Dibromophakellstatin = 473. Dibromopyrrole acid = 344. 4,5-Dibromo-1H-pyrrole-2-carboxamide = 345. 4,5-Dibromo-1H-pyrrole-2-carboxylic acid = 344. 3,4-Dibromo-1H-pyrrole-2,5-dione = 343. Dibromosceptrine = 474. 2,3-Dibromostyloguanidine = 475. 5,6-Dibromotryptamine = 956. 3,5-Dibromoverongiaquinol = 132. Dictazole A = 476. Dictyodendrin J = 414. 17,29-Didehydro-cylindramide Mg salt (2:1) = 601. Didemnidine A = 10. Didemnidine B = 11. Didemnimide A = 1013. Didemnimide B = 1014. Didemnimide C = 1015. Didemnimide D = 1016. Didemnoline A = 813. Didemnoline B = 814. Didemnoline C = 815. Didemnoline D = 816. Diguanidium salt of psammaplin A sulfate = 277. Dihomodehydrobatzelladine C = 88. Dihydrodeoxybromotopsentin = 736. 3,4-Dihydro-6-hydroxy-10,11-epoxymanzamine A = 898. 9,10-Dihydrokeramadine = 477. 3,4-Dihydrokeramamine A = 899. Dihydrolamellarin B = 405. 3,4-Dihydromanzamine A = 899. 3,4-Dihydromanzamine A N-oxide = 900.

409

3,4-Dihydromanzamine J N-oxide = 901. 4ξ,5-Dihydroodiline = 484. 2,2-Di-3-indolyl-3-indolone = 737. 4-[(Di-1H-indol-3-yl)methyl]phenol = 726. (3,5-Di-iodo-4-methoxyphenyl)ethylamine = 226. 3-(3,5-Diiodo-4-methoxyphenyl)-3ʹ-(3-iodo-4methoxyphenyl)-N,N’- (1,5-pentanediyl)bis (2-dimethylaminopropanamide) = 278. 9,10-Diisopentenylpaxilline = 1065. N,N-Dimethyl-5-bromotryptamine = 957. N,N-Dimethyl-5,6-dibromotryptamine = 958. 2-(3,3-Dimethylprop-1-ene)-costaclavine = 1102. 2-(3,3-Dimethylprop-1-ene)-epi-costaclavine = 1103. Dinorbatzelladine A = 89. Dinordehydrobatzelladine B = 90. Discodermindole = 1017. Dispacamide A = 478. Dispacamide B = 479. Dispacamide C = 480. Dispacamide D = 481. 15,34-Di-O-sulfatobastadin 7 = 279. Dixiamycin A = 782. Dixiamycin B = 783. 5-Dodecenyl-4-amino-3-hydroxybenzoate = 211. Domoic acid = 550. Dopamine = 227. Dorimidazole A = 1131. Dragmacidin D = 738. Dysidamide = 551. Dysideanin A = 1132. Dysideanin B = 817. Dysideapyrrolidone = 552. Dysidine (1977) = 553. Dysidine (2001) = 212. E Echinobetaine B = 1133. Echinosulfonic acid A = 739. Echinosulfonic acid B = 740. Echinosulfonic acid C = 741. Echinosulfonic acid C 1′′-deoxy = 742. Emerimidine A = 1087. Emerimidine B = 1088. Emindole DA = 1066. Emindole SB = 1067.

410

Index 1 Compound Name and Synonym Index

Emindole SB β-mannoside = 1068. Epolactaene = 554. Equisetin = 600. Estatin A = 12. Estatin B = 13. N-3′-Ethylaplysinopsin = 1018. 1-Ethyl-β-carboline = 818. 1-Ethyl-β-carboline-3-carboxylic acid = 819. Eudisin B = 865. Eudistalbin A = 820. Eudistomidin A = 821. Eudistomidin B = 822. Eudistomidin C = 823. Eudistomidin D = 824. Eudistomidin G = 825. Eudistomidin J = 826. Eudistomin A = 827. Eudistomin B = 828. Eudistomin C = 829. Eudistomin D = 830. Eudistomin E = 831. Eudistomin F = 832. Eudistomin G = 833. Eudistomin H = 834. Eudistomin I = 835. Eudistomin J = 836. Eudistomin K = 837. Eudistomin L = 838. Eudistomin M = 839. Eudistomin N = 840. Eudistomin O = 841. Eudistomin P = 842. Eudistomin Q = 843. Eudistomin U = 844. Eudistomin Y1 = 845. Eudistomin Y2 = 846. Eudistomin Y3 = 847. Eudistomin Y4 = 848. Eudistomin Y5 = 849. Eudistomin Y6 = 850. Eudistomin Y7 = 851. Eusynstyelamide = 14. Eusynstyelamide A = 14. Eusynstyelamide B = 15. ent-Eusynstyelamide B = 16. Eusynstyelamide C = 17. Eusynstyelamide D = 18. Eusynstyelamide E = 19. Eusynstyelamide F = 20.

F Fascaplysin = 852. Flavochristamide A = 135. Flavochristamide B = 136. Flustramine A = 982. Flustramine B = 983. Flustramine E = 984. Flustramine F = 985. Flustramine I = 986. Flustramine L = 987. N-Formyl-2- (4-hydroxyphenyl)acetamide = 137. 5-Formyl-1H-pyrrole-2-heneicosanenitrile = 376. 5-Formyl-1H-pyrrole-2-octadecanenitrile = 375. Fradcarbazole A = 792. Fradcarbazole B = 793. Fradcarbazole C = 794. Fromia monilis Alkaloid = 21. Fromiamycalin = 91. FumigaclavineB = 1104. Fumigaclavine C = 1105. Fuscusine = 62. G (±)-Gelliusine A = 959. (±)-Gelliusine B = 960. (±)-Gelliusine C = 961. (±)-Gelliusine D = 962. (±)-Gelliusine E = 963. (±)-Gelliusine F = 964. Geodin A = 601. Gesashidine A = 853. Giracodazole = 1134. Girolline = 1134. GlcNAc-TA = 1096. Gliocladine C = 994. Gonyautoxin I = 112. Gonyautoxin II = 113. Gonyautoxin III = 114. Gonyautoxin IV = 115. Gonyautoxin V = 116. Gonyautoxin VI = 117. Gonyautoxin VIII = 118. Granulatamide A = 681. Granulatamide B = 682. Grenadamide B = 138. Grenadamide C = 139. GTX1 = 112.

Index 1 Compound Name and Synonym Index

GTX2 = 113. GTX3 = 114. GTX4 = 115. Gymnastatin Q = 140. H Hainanerectamine B = 683. Hainanerectamine C = 854. Halichrome A = 743. Halocyamine A = 1019. Halocyamine B = 1020. Hapalindole A = 1047. 12-epi-Hapalindole C = 1048. 12-epi-Hapalindole E = 1049. 12-epi-Hapalindole G = 1050. 12-epi-Hapalindole H = 1051. 12-epi-Hapalindole J = 1052. 12-epi-Hapalindole Q = 1053. Hapalindole T = 1054. Hapalindolinone A = 1055. Hapalindolinone B = 1056. Harman = 855. Hemibastadin 2 = 280. (–)-Herbindole A = 684. (+)-Herbindole A = 685. (–)-Herbindole B = 686. (+)-Herbindole B = 687. (–)-Herbindole C = 688. (+)-Herbindole C = 689. Herdmanine E = 690. Herdmanine I = 691. Herdmanine J = 692. Herdmanine K = 693. Herdmanine K = 1021. Herdmanine L = 694. Hermitamide A = 228. Hermitamide B = 965. Heronamide C = 206. Heronapyrrole A = 346. Heronapyrrole B = 347. Heronapyrrole C = 348. Hexaacetylcelenamide A = 1106. Hexaacetylcelenamide B = 1107. 5-Hexadecyl-1H-pyrrole-2-carboxaldehyde = 349. 10,11,15,16,32,33-Hexahydro8-hydroxymanzamine A = 902. Hicksoane A = 695. Hicksoane B = 696.

411

Hicksoane C = 697. Homofascaplysin A = 856. Homopahutoxin = 2. Homotaurine = 3. Hordenine = 229. 3-(Hydroxyacetyl)-1H-indole = 698. 2-(4-Hydroxybenzoyl)-4(5)-(4-hydroxyphenyl)1H-imidazole = 1135. 2-Hydroxycircumdatin C = 175. 6-Hydroxycircumdatin C = 175. 6-Hydroxydiscodermindole = 1022. 3-(3-(2-Hydroxyethyl)-(1H-indol-2-yl)-3-(1H-indol3-yl)propane-1,2-diol) = 744. 3-(2-Hydroxyethyl)-6-prenylindole = 699. 2-(2-(3-Hydroxy-1-(1H-indol-3-yl)-2methoxypropyl)-1H-indol-3-yl) acetic acid = 745. 8-Hydroxymanzamine A = 903. ent-8-Hydroxymanzamine A = 904. 6-Hydroxymanzamine A = 905. 8-Hydroxymanzamine B = 906. 6-Hydroxymanzamine E = 907. 8-Hydroxymanzamine J = 904. N-[2-(4-Hydroxy-3-methoxyphenyl)ethyl]3-methyl-2-dodecenamide = 230. N-[2-(3-Hydroxy-4-methoxyphenyl)ethyl]3-methyl-2-dodecenamide = 231. N- (1ʹR-Hydroxymethyl-2-methoxyethyl)7S-methoxy-4E-eicosenamide = 141. Hydroxymoloka’iamine = 326. 2-Hydroxy-7-oxostaurosporine = 800. 3-Hydroxy-7-oxostaurosporine = 801. 2′-Hydroxypaxilline = 1069. 19-Hydroxypenitrem A = 1070. 19-Hydroxypenitrem E = 1071. (S)-p-Hydroxyphenopyrrozin = 627. N-[2-(4-Hydroxyphenyl)ethyl]-3-methyl2-dodecenamide = 232. 36R-Hydroxy-ptilomycalin A = 82. 22α-Hydroxy-shearinine A = 1081. 11-Hydroxystaurosporine = 795. 5ʹ-Hydroxystaurosporine = 796. N-Hydroxy-6-epi-stephacidin A = 1108. Hydroxytyramine = 227. 8-Hydroxy-1-vinyl-β-carboline = 857. (10Z)-Hymenialdisine = 482. Hymenidine = 483. (–)-Hymenine‡ = 484. Hyrtimomine A = 746.

412

Index 1 Compound Name and Synonym Index

Hyrtimomine D = 747. Hyrtimomine E = 748. Hyrtimomine F = 749. Hyrtimomine G = 750. Hyrtiocarboline = 858. Hyrtioerectine D = 859. Hyrtioerectine E = 860. Hyrtioerectine F = 861. Hyrtiomanzamine = 862. Hyrtioreticulin B = 863. Hyrtioreticulin E = 864. I Ianthellamide A = 327. Ianthelliformisamine A = 22. Ianthelliformisamine B = 23. Ianthelliformisamine C = 24. Iheyamine A = 752. Iheyamine B = 753. Indimicin B = 797. Indolactam V = 1039. 1H-Indole-3-carboxylic acid methyl ester = 700. 3- (3-Indolyl)acrylamide = 142. 2-(1H-Indol-3-yl)ethyl-5-hydroxypentanoate = 701. 2-(1H-Indol-3-yl)ethyl-2-hydroxypropanoate = 702. 3-Indolylglyoxylic acid = 703. 3-Indolylglyoxylic acid methyl ester = 704. 6-(1H-Indol-3-yl)-5-methyl-3,5-heptadien-2-one = 705. (1H-indol-3-yl) oxoacetamide = 966. (1H-Indol-3-yl) oxoacetic acid methyl ester = 706. (6S,7R,10E,14E)-16-(1H-Indol-3-yl)-2,6,10,14tetramethylhexadeca-2,10,14-triene-6,7diol = 1072. Iotrochamide A = 180. Iotrochamide B = 181. Ircinal A = 908. Ircinal B = 909. Ircinamine = 555. Ircinamine B = 350. Ircinol A = 910. Isobastadin 4 = 258. Isobengamide E = 207. Isobromodeoxytopsentin = 1023. Isobromotopsentin = 1024.

Isocrambescidin 800 = 92. Iso-α-cyclopiazonic acid = 1057. Isodomoic acid A = 556. Isodomoic acid B = 557. Isodomoic acid C = 558. Isodomoic acid G = 559. Isodomoic acid H = 560. Isoeudistomin U = 865. Isofistularin 3 = 281. Isonaamidine C = 1136. Isonaamidine D = 1137. Isonaamidine E = 1138. Isonotoamide B = 1109. Isopalauamine = 515. 21-Isopentenylpaxilline = 1073. 9-Isopentenylpaxilline = 1073. Isoplysin A = 1025. Isoptilocaulin = 72. Iso-trans-trikentrin B = 707. J Jamaicamide A = 561. Jamaicamide B = 562. Jamaicamide C = 563. Janthielamide A = 143. JBIR 31 = 1040. JBIR 66 = 144. JBIR 81 = 967. JBIR 82 = 968. JBIR 102 = 630. JBIR 44 = 282. K Kauluamine = 911. neo-Kauluamine = 912. Kealiinine A = 1139. Keramadine = 485. Keramamine B = 913. Keronopsin A1 = 415. Keronopsin A2 = 416. Keronopsin B1 = 417. Keronopsin B2 = 418. 11-Ketofistularin 3 = 283. Kimbeamide A = 145. Konbamidin = 969. Konbuacidin A = 486. Kororamide A = 970. Korormicin A = 146. Kottamide A = 971.

Index 1 Compound Name and Synonym Index

Kottamide B = 972. Kottamide C = 973. Kottamide D = 974. L Lamellarin A = 397. Lamellarin A1 = 398. Lamellarin A2 = 399. Lamellarin A3 = 400. Lamellarin A4 = 401. Lamellarin A5 = 402. Lamellarin A6 = 403. Lamellarin B = 404. Lamellarin C = 405. Lamellarin D = 406. Lamellarin I = 407. Lamellarin J = 408. Lamellarin K = 409. Lamellarin M = 410. Lamellarin R = 351. Lamellarin α 20-sulfate = 411. Lamellarin β = 412. (–)-(R)-Leptoclinidamine B = 975. Leptosin O = 995. Leptosin P = 996. Leucettamidine = 1140. Leucettamine A = 1141. Leucettamine B = 1142. Limazepine G = 176. Lipogrammistin A = 25. Lipopurealin A = 1143. Lipopurealin B = 1144. Lipopurealin C = 1145. Lorneamide A = 147. Lukianol A = 419. Lukianol B = 420. Lynamicin A = 754. Lynamicin B = 755. Lynamicin C = 756. Lynamicin D = 757. Lynamicin E = 758. Lyngbyatoxin A = 1041. Lyngbyatoxin B = 1042. Lyngbyatoxin C = 1043. M Maeganedin A = 914. Magnesidin = 602. Malonganenone B = 1146.

413

Malonganenone F = 1147. Malonganenone G = 1148. Malonganenone K = 148. Manadomanzamine A = 915. Manadomanzamine B = 916. Mangrovamide C = 1110. Manzamine A = 917. Manzamine A N-oxide = 918. Manzamine B = 919. Manzamine C = 866. Manzamine D = 920. Manzamine E = 921. Manzamine F = 913. ent-Manzamine F = 922. Manzamine G = 903. ent-Manzamine G = 904. Manzamine H = 923. Manzamine J = 924. Manzamine J N-oxide = 900. Manzamine L = 925. Manzamine X = 926. Manzamine Y = 905. Mariline A1 = 1089. Mariline A2 = 1090. Mariline B = 1091. Mariline C = 1092. Marinacarboline A = 867. Marinacarboline B = 868. Marinacarboline C = 869. Marinacarboline D = 870. Marineosin A = 421. Marineosin B = 422. Marinopyrrole A = 423. Marinopyrrole B = 424. (–)-Marinopyrrole C = 425. (±)-Marinopyrrole F = 426. Mauritamide A = 487. Mauritiamine = 488. MD113068-6 = 213. Meleagrin = 1026. Meleagrin B = 1027. Meleagrin D = 1028. Meleagrin E = 1029. Merobatzelladine A = 93. Merobatzelladine B = 94. Metagenediindole A = 759. Metagenetriindole A = 760. 5-Methoxy-2,6-dimethyl-2H-isoindole-4,7-dione = 1093.

414

Index 1 Compound Name and Synonym Index

5-Methoxy-1H-indole-4,7-dione = 708. 6-Methoxy-1H-indole-4,7-dione = 709. 4-Methoxy-5-[(3-methoxy-5-pyrrol-2-yl-2H-pyrrol2-ylidene)methyl]-2,2′-bipyrrole = 427. 22α-Methoxy-shearinine A = 1083. N1-Methylalternatamide B = 940. N-3′-Methylaplysinopsin = 1030. 27-O-Methylasporyzine C = 1074. 1-Methyl-9H-carbazole = 784. 1-Methyl-β-carboline = 855. Methyl 4- (2,3-dibromo-4,5dihydroxybenzylamino)-4-oxobutanoate = 149. N-Methyl-5,6-dibromotryptamine = 976. 3,3′-Methylenebisindole = 761. N14-Methyleudistomidin C = 871. N2-Methyleudistomin D = 872. N2-Methyleudistomin J = 873. 4ʹ-N-Methyl-5ʹ-hydroxystaurosporine = 798. 1-Methyl indole-3-carboxamide = 710. 5-Methyl-1H-indole-4,7-dione = 711. 3-O-Methylmassadine chloride = 489. Methylpendolmycin-14-O-α-glucoside = 1111. 5-(14-Methylpentadecyl)-1H-pyrrole2-carboxaldehyde = 352. 3-Methyl-N- (2′-phenylethyl)-butyramide = 150. 3-((6-Methylpyrazin-2-yl)methyl)-1H-indole = 712. 2-Methyl-9H-pyrido[3,4b]indole-3-carboxylic acid = 874. 5-(13-Methyltetradecyl)-1H-pyrrole2-carboxaldehyde = 353. 1-Methyl-2,3,5-tribromoindole = 713. Milnamide A = 875. Mirabilin B = 73. Moiramide B = 621. Molokaiakitamide = 328. Molokaiamine = 329. Monanchocidin = 95. Monanchocidin A = 95. Monanchocidin B = 96. Monanchocidin C = 97. Monanchocidin D = 98. Monanchocidin E = 99. Monanchomycalin C = 63. Monobromoisophakellin = 490. Monodontamide A = 26. Monodontamide B = 27.

Monodontamide C = 28. Monodontamide D = 29. Monodontamide E = 30. Motualevic acid A = 151. Motualevic acid B = 152. Motualevic acid C = 153. Motualevic acid E = 154. Motuporamine A = 31. Motuporamine B = 32. Motuporamine C = 33. Mukanadine A = 481. Mukanadine F = 491. Mycalazal 2 = 354. Mycalazal 3 = 355. Mycalazal 14 = 356. Mycalazal 15 = 357. Mycalazal 16 = 358. Mycalazal 17 = 359. Mycalazal 18 = 360. Mycalazal 19 = 361. Mycalazal 20 = 362. Mycalazol 1 = 363. Mycalazol 2 = 364. Mycalazol 3 = 365. Mycalazol 4 = 366. Mycalazol 5 = 367. Mycalazol 6 = 368. Mycalazol 7 = 369. Mycalazol 8 = 370. Mycalazol 9 = 371. Mycalazol 10 = 372. Mycalazol 11 = 373. Mycalazol 12 = 374. Mycalenitrile 1 = 375. Mycalenitrile 2 = 376. Mycalenitrile 4 = 377. Mycalenitrile 5 = 378. Mycalenitrile 6 = 379. Mycalenitrile 7 = 380. Mycalenitrile 8 = 381. Mycalenitrile 9 = 382. Mycalenitrile 10 = 383. Mycalenitrile 11 = 384. Mycalenitrile 12 = 385. Mycalenitrile 13 = 386. Mycalenitrile 14 = 387. Mycapolyol A = 564. Mycapolyol B = 565. Mycapolyol C = 566.

Index 1 Compound Name and Synonym Index

Mycapolyol D = 567. Mycapolyol E = 568. Mycapolyol F = 569. N Naamidine A = 1149. Naamidine F = 1150. Nagelamide A = 492. Nagelamide B = 493. Nagelamide C = 494. Nagelamide D = 495. Nagelamide E = 496. Nagelamide F = 497. Nagelamide G = 498. Nagelamide H = 499. Nagelamide O = 500. Nagelamide U = 64. Nagelamide W = 501. Nagelamide X = 502. Nagelamide Y = 503. Nakadomarin A = 927. Nakamuric acid = 504. Nakamuric acid methyl ester = 505. Namalide = 182. (E)-Narain = 65. (Z)-Narain = 66. Neoaplaminone = 284. Neoaplaminone sulfate = 285. Neocomplanine A = 155. Neocomplanine B = 156. Neoechinulin A = 997. Neoechinulin B = 998. Neofolitispate 1 = 100. Neofolitispate 2 = 101. Neofolitispate 3 = 102. Neosaxitoxin = 119. Nigribactin = 34. Nitropyrrolin A = 388. Nitropyrrolin B‡ = 389. Nitropyrrolin C = 390. Nitropyrrolin D = 391. Nitropyrrolin E = 392. Nitrosporeusine A = 622. Nitrosporeusine B = 623. Norbatzelladine A = 103. Norbatzelladine L = 104. Norcardioazine A = 999. Nordomoic acid = 570. 15-Norpseurotin A = 571.

11-Nortetrodotoxin = 107. 11-Nortetrodotoxin-6S-ol = 107. Nortopsentin A = 762. Nortopsentin B = 763. Nortopsentin C = 764. Nortopsentin D = 765. Notoamide A = 1112. (–)-Notoamide B = 1113. Notoamide I = 1114. O Oceanapia Bromotyrosine alkaloid = 35. 21-Odeacetylcytochalasin Q = 658. Opacaline A = 876. Opacaline B = 877. (E)-Oroidin = 506. 12,28-Oxa-8-hydroxymanzamine A = 928. 12,34-Oxa-6-hydroxymanzamine E = 929. 12,28-Oxamanzamine E = 930. Oxiamycin = 785. 3-Oximido-ethyl-6-prenylindole = 977. 7-Oxo-8,9-dihydroxy-4′-Ndemethylstaurosporine = 799. 6-Oxofascaplysin = 878. 11-Oxofistularin 3 = 283. 7-Oxo-2-hydroxystaurosporine = 800. 7-Oxo-3-hydroxystaurosporine = 801. α-Oxo-1H-indole-3-acetic acid methyl ester = 704. 2-Oxoteleocidin A1 = 1040. 7-Oxo-3,8,9-trihydroxystaurosporine = 802. Oxysceptrin = 507. Oxysceptrine = 507. P Palauamine = 508. Palau‘amine = 508. Palmyrrolinone = 393. Paspaline = 1075. Paspalitrem A = 1076. Pavettine = 879. Paxilline = 1077. Penicillazine = 168. Penicillenol A1 = 603. Penicillenol A2 = 604. Penicillenol B1 = 605. Penicillenol B2 = 606. Penipacid A = 214. Penipacid E = 215.

415

416

Index 1 Compound Name and Synonym Index

Penipaline A = 880. Penipaline B = 881. Penipaline C = 714. Penochalasin A = 659. Penochalasin B = 660. Penochalasin C = 661. Penochalasin D = 662. Penochalasin E = 663. Penochalasin F = 664. Penochalasin G = 665. Penochalasin H = 666. Pentaacetylcelenamide C = 1115. Pentabromopseudilin = 394. 5-Pentadecyl-1H-pyrrole-2-carboxaldehyde = 395. N,N′-(1,5-Pentanediyl)bis[3-(3,5-diiodo4-methoxyphenyl)-2-dimethylamino-propanamide] = 286. Phaeophytin A = 527. Phenethyl 5-oxo-L-prolinate = 208. (R)-Phenopyrrozin = 628. N- (2-Phenylethyl)-9hydroxyhexadecacarboxamide = 233. N- (2-Phenylethyl)-9-oxohexadecacarboxamide = 234. Pheophorbide a = 528. Pheophytin a = 529. Phidianidine A = 36. Phidianidine B = 37. Phomasetin = 607. Phorbatopsin A = 1151. Phorbatopsin B = 1152. Phorbatopsin C = 1153. Pibocine A = 1116. Pibocine B = 1117. Piclavine B = 631. Piclavine C = 632. Pitiamide A = 157. Plakohypaphorine B = 978. Plakohypaphorine C = 979. Plakohypaphorine D = 980. Plakoridine A = 572. Plakortamine A = 882. Plakortamine B = 883. Plakortamine C = 884. Plakortamine D = 885. Plectosphaeroic acid A = 1000. Plectosphaeroic acid B = 1001.

Plectosphaeroic acid C = 1002. PM050489 = 158. PM060184 = 159. (±)-Polyandrocarpamide D = 1031. Pre-neo-kauluamine = 931. Prodigiosin = 530. Protogonyautoxin 3 = 122. Psammaplin A = 287. Psammaplin B = 288. Psammaplin D = 289. Psammaplin E = 290. Psammaplin F = 291. Psammaplin G = 292. Psammaplin I = 293. Psammaplysene A = 294. Psammaplysene B = 295. Psammaplysene C = 296. Psammaplysene D = 297. Pseudoceramine = 273. Pseudoceramine B = 38. Pseudoceratidine = 39. Pseudoceratin A = 298. Pseudoceratin B = 299. Pseurotin A = 573. (+)-Ptilocaulin = 74. Ptilomycalin A = 105. Pulchellalactam = 574. Pulchranin A = 67. Pulchranin B = 68. Pulchranin C = 69. Purealidin A = 1154. Purealidin C = 300. Purealidin D = 1155. Purealidin E = 1156. Purealidin F = 301. Purealidin G = 235. Purealidin M = 1157. Purealidin N = 1158. Purpuramine A = 330. Purpuramine B = 331. Purpuramine C = 302. Purpuramine D = 303. Purpuramine E = 304. Purpuramine F = 305. Purpuramine G = 306. Purpuramine H = 241. Purpuramine I = 307. Purpuramine J = 308.

Index 1 Compound Name and Synonym Index

Purpurealidin B = 309. Pyraxinine = 70. Pyronaamidine 9-N-methylimine = 1159. R Racemosin A = 766. Racemosin B = 767. Racemosine A = 766. Racemosine B = 767. Rexostatine = 40. N-α-L-Rhamnopyranosyl-tjipanazole D = 807. Rhapsamine = 41. Rhopaladin B = 768. Rhopaladin C = 769. Rivularin C = 774. Rivularin D1 = 770. Rivularin D3 = 775. Roquefortine C = 1003. Roquefortine F = 1004. Roquefortine G = 1005. Roquefortine H = 1006. Roquefortine I = 1007. Rosellichalasin = 667. Rubroside A = 608. Rubroside B = 609. Rubroside C = 610. Rubroside D = 611. Rubroside E = 612. Rubroside F = 613. Rubroside G = 614. Rubroside H = 615. S Saxitoxin = 120. Scalusamide A = 575. Sceptrine = 509. (–)-Sclerotiamide = 1118. Secobatzelline A = 1119. Secobatzelline B = 1120. Secofascaplysic acid = 886. Serinolamide A = 160. Serinolamide B = 161. Sesquibastadin = 310. Shearinine A = 1078. Shearinine B = 1079. Shearinine C = 1080. 22α-Shearinine D = 1081. Shearinine E (Smetanina, 2007) = 1082.

Shearinine E (Xu, 2007) = 1083. Shearinine F (Smetanina, 2007) = 1084. Shearinine G = 1085. Shishididemniol A = 332. Shishididemniol B = 333. Sinulamide = 42. Sinulasulfone = 162. Sinulasulfoxide = 163. Slagenine A = 510. Slagenine B = 511. Slagenine C = 512. Sodium salt of psammaplin A sulfate = 311. Somocystinamide A = 164. Spiroindimicin B = 771. Spiroindimicin C = 772. Spiroindimicin D = 773. Spongiacidin A = 513. Spongiacidin B = 514. Spongiacidin C = 466. Spongiacidin D = 453. Spongotine B = 736. Stachybotrin D = 1094. Stachyflin = 1095. Stachyin B = 1058. Staurosporine = 803. Staurosporine aglycone = 804. Stellettamide B = 633. Stellettazole D = 1160. Stephacidin A = 1121. Stephacidin B = 1122. Storniamide A = 428. Storniamide B = 429. Storniamide C = 430. Storniamide D = 431. Streptocarbazole A = 805. Streptosetin A = 616. Stylissadine A = 432. Stylissadine B = 433. Styloguanidine = 515. Suberedamine A = 312. Suberedamine B = 313. 10-O-Sulfatobastadin 3 = 314. Sulfobacin A = 136. 34-Sulfobastadin 13 = 315. 1-O-Sulfohemibastadin 1 = 316. 4-O-Sulfohemibastadin 1 = 316. 1-O-Sulfohemibastadin 2 = 317. 4-O-Sulfohemibastadin 2 = 317.

417

418

Index 1 Compound Name and Synonym Index

15-O-Sulfonatobastadin 11 = 318. Surugatoxin = 1123. Sventrine = 516. Symphyocladin G = 43. Synechobactin A = 165. T Tambjamine A = 434. Tambjamine B = 435. Tambjamine C = 436. Tambjamine D = 437. Tambjamine E = 438. Tambjamine F = 439. Tambjamine G = 440. Tambjamine H = 441. Tambjamine I = 442. Tambjamine J = 443. Tambjamine K = 444. Taurine = 4. Tauroacidin A = 517. Tauroacidin B = 518. Taurodispacamide A = 519. Teleocidin A1 = 1041. Tenacibactin A = 44. Tenacibactin B = 45. Tenacibactin C = 46. Tenacibactin D = 47. Terremide A = 166. Terremide B = 167. Tetraacetylclionamide = 981. 2,2′,5,5′-Tetrabromo-3,3′-bi-1H-indole = 774. 2,3,5,6-Tetrabromo-1H-indole = 715. (+)-2,3ʹ,5,5ʹ-Tetrabromo-7ʹ-methoxy-3,4ʹ-bi-1Hindole = 775. 2,3,5,6-Tetrabromo-1-methyl-1H-indole = 716. 2,7-Tetradecadienyl-4-amino-3hydroxybenzoate = 216. (2S,3E,5Z)-3,5,13-Tetradecatrien-2-amine = 5. 7Z-Tetradecenyl-4-amino-3-hydroxybenzoate = 217. 1,2,3,4-Tetrahydro-2-N-methyl-8hydroxymanzamine A = 932. 2,3,4,5-Tetrahydro-3,5-dihydroxy-6H-1,5benzoxazocin-6-one = 209. 1,2,3,4-Tetrahydro-1,1-dimethyl-β-carboline-3βcarboxylic acid = 887. 1,2,3,4-Tetrahydro-8-hydroxymanzamine A = 933.

1β,2,3,4-Tetrahydromanzamine B = 934. Tetrodotoxin = 108. 4-epi-Tetrodotoxin = 109. 6-epi-Tetrodotoxin = 110. Tiruchanduramine = 888. Tjipanazole A1 = 806. Tjipanazole A2 = 807. Tokaradine A = 319. Tokaradine B = 320. Tokaradine C = 48. Tolyporphin A = 531. Tolyporphin B = 532. Tolyporphin C = 533. Tolyporphin D = 534. Tolyporphin E = 535. Tolyporphin F = 536. Tolyporphin G = 537. Tolyporphin H = 538. Tolyporphin I = 539. Topsentin = 776. Topsentin B2 = 777. Toxin C1 = 121. Toxin C3 = 122. Toxin C4 = 123. Toxin PX1 = 121. Trachycladindole A = 1032. Trachycladindole B = 1033. Trachycladindole C = 1034. Trachycladindole D = 1035. Trachycladindole E = 1036. Trachycladindole F = 1037. Tramiprosate = 3. 2,5,6-Tribromo-N-methylgramine = 717. 2,5,6-Tribromo-N-methylgramine N-oxide = 718. 2,3,6-Tribromo-1-methyl-1H-indole = 719. 2,3,4-Tribromo-1H-pyrrole = 396. Trichodermamide A = 168. Trichodermamide B = 169. 5,6,11-Trideoxytetrodotoxin = 111. (1′′S,3′′S)-Trikentrin A = 720. (1′′R,3′′S)-Trikentrin A = 721. cis-Trikentrin B = 722. N′,N′′,N′′-Trimethyl-N- (3-methyl-2Z, 4E-dodecadienoyl)spermidine = 49. N′,N′,N′-Trimethyl-N- (3-methyl-2,4dodecadienoyl)spermidine = 50.

Index 1 Compound Name and Synonym Index

N′,N′,N′-Trimethyl-N- (3-methyldodecanoyl) spermidine = 51. N′,N′′,N′′-Trimethyl-N- (3-methyl-2Z-dodecenoyl) spermidine = 52. N′,N′,N′-Trimethyl-N- (3-methyl-2E-dodecenoyl) spermidine = 53. N′,N′′,N′′-Trimethyl-N- (5-methyl-3tetradecenoyl)spermidine = 54. Tryptophol = 723. TTX = 108. Tubastrindole B = 520. Tubastrine = 71. Turbinamide = 170. Turbotoxin A = 236. Turbotoxin B = 237. U Ulosantoin = 1161. V Villagorgin A = 889. Villatamine A = 576. Villatamine B = 577. 1-Vinyl-β-carboline = 879.

X Xanthocillin X = 334. Xestocyclamine A = 935. Xestomanzamine A = 890. Xestomanzamine B = 891. Xiamycin = 786. Xiamycin A = 786. Xiamycin A methyl ester = 787. Xiamycin B = 788. Xylarisin = 668. Xylarisin A = 668. Y Ypaoamide = 578. Z Zamamidine A = 936. Zamamidine B = 937. Zamamidine C = 938. Zamamiphidin A = 939. Zopfiellamide A = 617. Zopfiellamide B = 618. Zorrimidazolone = 1162.

419

Index 2 Compound Molecular Formula Index The Molecular Formula Index of Volume 3 lists the molecular formulae of all 1,162 active isolated compounds from marine organisms given in the HAMNP Volume 3 in Hill convention order. Under a bold formula, all related compound names following code numbers are listed in the code number order too. C2 C2H7NO3S – Taurine, 4. C3 C3H9NO3S – Homotaurine, 3. C4 C4HBr2NO2 – 3,4-Dibromomaleimide, 343. C4H2BrNO2 – 3-Bromo-1H-pyrrole-2,5-dione, 339. C4H2Br3N – 2,3,4-Tribromo-1H-pyrrole, 396. C5 C5H3Br2NO2 – Dibromopyrrole acid, 344. C5H4Br2N2O – 4,5-Dibromo-1H-pyrrole-2-carboxamide, 345. C5H9N2O5P – Ulosantoin, 1161 C6 C6H7NO – o-Aminophenol, 210. C6H8N4 – Pyraxinine, 70. C6H11ClN4O – Girolline, 1134 C7 C7H8Br2N2O2 – 4,5-Dibromo-N2-methoxymethyl-1H-pyrrole2-carboxamide, 134. C7H11N3O2 – Aminozooanemonin, 1124 C7H17N4O4P – Anatoxin a (S), 1125

C8 C8H3Br4N – 2,3,5,6-Tetrabromo-1H-indole, 715. C8H5Br2N – 3,6-Dibromo-1H-indole, 680. C8H6BrNO – 6-Bromo-5-hydroxy-1H-indole, 672. C8H6BrNO2 – 6-Bromo-4,5-dihydroxyindole, 670. – 6-Bromo-4,7-dihydroxyindole, 671. C8H6ClN – 3-Chloro-1H-indole, 675. C8H7Br2NO3 – 2,6-Dibromo-4-acetamido-4hydroxycyclohexa-dienone, 132. C8H8BrNO3 – 3-Bromo-5-hydroxy-4-methoxybenzamide, 129. C8H8BrNO4 – 7-Bromocavernicolenone, 199. C8H10BrNO – 4- (2-Aminoethyl)-2-bromophenol, 219. C8H11NO2 – Dopamine, 227. C8H12N2O3 – Echinobetaine B, 1133 C8H14N3O2S1+ – Dysideanin A, 1132 C9 C9H5Br4N – 2,3,5,6-Tetrabromo-1-methyl-1H-indole, 716. C9H6BrNO – 6-Bromoindole-3-carbaldehyde, 673. C9H6Br3N – 1-Methyl-2,3,5-tribromoindole, 713. – 2,3,6-Tribromo-1-methyl-1H-indole, 719. C9H7Br2NO2 – Convolutamydine C, 678. C9H7NO2 – 5-Methyl-1H-indole-4,7-dione, 711.

Index 2 Compound Molecular Formula Index

C9H7NO3 – 5-Methoxy-1H-indole-4,7-dione, 708. – 6-Methoxy-1H-indole-4,7-dione, 709. C9H9NO3 – N-Formyl-2- (4-hydroxyphenyl)acetamide, 137. C9H10BrNO3 – 2-(3-Bromo-5-hydroxy-4-methoxyphenyl) acetamide, 130. C9H11I2NO – (3,5-Di-iodo-4-methoxyphenyl)ethylamine, 226. C9H11N3O2 – Tubastrine, 71. C9H12N3O1+ – 3ʹ-Deoxytubastrine, 61. C9H13NO – Pulchellalactam, 574. C10 C10H4Br5NO – Pentabromopseudilin, 394. C10H6Br2N2O2 – (1H-indol-3-yl) oxoacetamide, 966. C10H7Br2N5 – Ageladine A, 445. C10H7Br2NO2 – Convolutamydine D, 679. C10H7NO3 – 3-Indolylglyoxylic acid, 703. C10H8BrNO2 – 6-Bromo-1H-indole-3-carboxylic acid methyl ester, 674. C10H8Br2ClNO2 – Convolutamydine B, 677. C10H9ClN2O4 – Secobatzelline B, 1120 C10H9NO2 – 3-(Hydroxyacetyl)-1H-indole, 698. – 1H-Indole-3-carboxylic acid methyl ester, 700. C10H9N3O2 – Phorbatopsin A, 1151 C10H10BrN3O – Tambjamine B, 435. C10H10Br2N2 – 5,6-Dibromotryptamine, 956. C10H10ClN3O3 – Secobatzelline A, 1119 C10H10N2O – 1-Methyl indole-3-carboxamide, 710.

C10H11NO – Tryptophol, 723. C10H11NO4 – 2,3,4,5-Tetrahydro-3,5-dihydroxy-6H-1, 5-benzoxazocin-6-one, 209. – Emerimidine A, 1087 – Emerimidine B, 1088 C10H11N3O – Tambjamine A, 434. C10H11N3O2 – Phorbatopsin C, 1153 C10H11N3O3 – Phorbatopsin B, 1152 C10H12Br3NO – Convolutamine F, 225. C10H13NO2 – N-Acetyltyramine, 218. C10H15NO – Hordenine, 229. C10H15N3O7 – 11-Nortetrodotoxin, 107. C10H17N7O11S2 – Gonyautoxin VIII, 118. C10H17N7O12S2 – Toxin C3, 122. – Toxin C4, 123. C10H17N7O4 – Saxitoxin, 120. C10H17N7O7S – Gonyautoxin V, 116. C10H17N7O8S – Gonyautoxin II, 113. – Gonyautoxin III, 114. C10H17N7O9S – Gonyautoxin I, 112. – Gonyautoxin IV, 115. C10H18N7O8S – Gonyautoxin VI, 117. C10H19N7O52+ – Neosaxitoxin, 119. C11 C11H7BrN2 – Eudistomin N, 840. – Eudistomin O, 841. C11H7BrN2O – Eudistomin D, 830. – Eudistomin J 836.

421

422

Index 2 Compound Molecular Formula Index

C11H7Br2NO3 – (1H-Indol-3-yl) oxoacetic acid methyl ester, 706. C11H9BrN4O3 – (Z)-Axinohydantoin, 453. C11H9Br2N5O2 – (Z)-3-Bromohymenialdisine, 455. – Spongiacidin A, 513. C11H9Br2NO3 – Convalutamydine A, 676. C11H9Br2NO4 – 3-(2,3-Dibromo-4,5-dihydroxybenzyl) pyrrolidine-2,5-dione, 620. C11H9NO3 – 3-Indolylglyoxylic acid methyl ester, 704. C11H10BrN5O2 – (10Z)-Hymenialdisine, 482. – Spongiacidin B, 514. C11H10Br2ClN5O2 – 12-Chloro-11-hydroxyldibromoisophakellin, 459. – 12-Chloro-11-hydroxydibromoisophakellin, 1128 C11H10Br2N4 – Discodermindole, 1017. C11H10Br2N4O – 6-Hydroxydiscodermindole, 1022. C11H10Br2N4O2 – Dibromophakellstatin, 473. C11H10Br2N4O4 – Mukanadine F, 491. C11H10N2O – 3- (3-Indolyl)acrylamide, 142. C11H10N4O3 – (Z)-Debromoaxinohydantoin, 466. C11H11BrN4O3 – Agelastatin D, 448. C11H11Br2NO5 – 4-(2,3-Dibromo-4,5-dihydroxybenzylamino)-4oxobutanoic acid, 133. C11H11Br2N5O – (–)-Hymenine‡, 484. – (E)-Oroidin, 506. C11H11Br2N5O2 – Dibromoagelaspongin, 470. – Dispacamide A, 478. C11H11Br2N5O3 – Dispacamide C, 480.

C11H11NO3 – MD113068-6, 213. – 5-Methoxy-2,6-dimethyl-2H-isoindole-4,7dione, 1093 C11H11N5O2 – (10Z)-Debromohymenialdisine, 467. C11H12BrN5O – Hymenidine, 483. – Monobromoisophakellin, 490. C11H12BrN5O2 – Dispacamide B, 479. C11H12BrN5O3 – Dispacamide D, 481. C11H12Br2N2 – N-Methyl-5,6-dibromotryptamine, 976. C11H13BrN2O4 – Damipipecoline, 341. C11H13BrN4O4 – Slagenine A, 510. C11H13NO3 – Mariline C, 1092 C11H13N3O – Dorimidazole A, 1131 C11H13N3O4 – Zorrimidazolone, 1162 C11H13N5O – Clathrodine, 464. C11H16Br2N2O – Molokaiamine, 329. C11H16Br2N2O2 – Hydroxymoloka’iamine, 326. C11H17N3O51+ – 5,6,11-Trideoxytetrodotoxin, 111. C11H17N3O6S – (E)-Narain, 65. – (Z)-Narain, 66. C11H17N3O7 – 11-Deoxytetrodotoxin, 106. C11H17N3O8 – Tetrodotoxin, 108. – 4-epi-Tetrodotoxin, 109. – 6-epi-Tetrodotoxin, 110. C11H17N7O11S2 – Toxin C1, 121. C12 C12H9BrN2O – Eudistomidin D 824.

Index 2 Compound Molecular Formula Index

C12H10BrN2O1+ – N2-Methyleudistomin D, 872. – N2-Methyleudistomin J, 873. C12H10N2 – Harman, 855. C12H10N2O3 – Penipacid E, 215. C12H11NO2 – Hainanerectamine B, 683. C12H11N3O3 – (±)-Polyandrocarpamide D, 1031. – Leucettamine B, 1142 C12H12BrN3O3S – Psammaplin B, 288. C12H13BrN4O3 – (–)-Agelastatin A, 446. C12H13BrN4O4 – Agelastatin C, 447. C12H13Br2NO5 – Methyl 4-(2,3-dibromo-4,5-dihydroxybenzylamino)-4-oxobutanoate, 149. C12H13Br2N5O – Sventrine, 516. C12H13Br3N2 – 2,5,6-Tribromo-N-methylgramine, 717. C12H13Br3N2O – 2,5,6-Tribromo-N-methylgramine N-oxide, 718. C12H14BrN3O – Tambjamine G, 440. C12H14BrN5O – Keramadine, 485. C12H14Br2N2 – N,N-Dimethyl-5,6-dibromotryptamine, 958. C12H15BrN2 – N,N-Dimethyl-5-bromotryptamine, 957. C12H15BrN2O4 – Damituricine, 342. C12H15BrN2O5S – Psammaplin I, 293. C12H15BrN4O3 – Clathramide C, 462. – Clathramide D, 463. C12H15BrN4O4 – Slagenine B, 511. – Slagenine C, 512. C12H15NO4 – Palmyrrolinone, 393. C12H15N3O – Tambjamine E, 438.

423

C12H15N3O3 – 2-[ (2-Acetamidopropanoyl)amino]benzamide, 124. C12H16BrN5O – 9,10-Dihydrokeramadine, 477. C12H16Br2N8O2+ – Nagelamide W, 501. C12H16Br3NO2 – Convolutamine C, 224. C12H18Br2N2O2 – Ceratinine A, 321. C12H25N3O – Pulchranin C, 69. C13 C13H9BrN2 – Plakortamine B, 883. C13H10Br2N4O – (8E)-5,6-Dibromo-2′-N-demethyl-aplysinopsin, 1011. – (8Z)-5,6-Dibromo-2′-N-demethyl-aplysinopsin, 1012. C13H10N2 – Pavettine, 879. C13H10N2O – 8-Hydroxy-1-vinyl-β-carboline, 857. C13H10N2O2 – 2-Methyl-9H-pyrido[3,4b]indole-3-carboxylic acid, 874. C13H11N – 1-Methyl-9H-carbazole, 784. C13H12N2 – 1-Ethyl-β-carboline, 818. C13H13BrN4O2 – Trachycladindole A, 1032. C13H13BrN4O3 – Trachycladindole C, 1034. C13H13NO2 – (R)-Phenopyrrozin, 628. C13H13NO3 – (S)-p-Hydroxyphenopyrrozin, 627. C13H14Br2N4O – Aplicyanin E, 57. C13H14N2O3 – Hyrtioreticulin E, 864. C13H14N2O4 – Konbamidin, 969. C13H15BrN2O2 – (−)-5-Bromo-N,N-dimethyltryptophan, 945.

424

Index 2 Compound Molecular Formula Index

C13H15Br2N3O2 – Ceratinamine, 273. C13H15NO3 – Phenethyl 5-oxo-L-prolinate, 208. – 2-(1H-Indol-3-yl)ethyl-2-hydroxypropanoate, 702. C13H16BrN3O – Tambjamine H, 441. C13H16Br2N2O2 – Ceratinine B, 322. C13H16Br2N6O4S – Taurodispacamide A, 519. C13H16Br2N6O5S – Tauroacidin A, 517. C13H16Br3NO2 – Convolutamine D, 324. C13H17BrN4O3 – Clathramide A, 460. – Clathramide B, 461. C13H17BrN6O5S – Tauroacidin B, 518. C13H17Br2N3O3 – Molokaiakitamide, 328. C13H17N21+ – Conicamine, 952. C13H18Br2N2O6S – Ianthellamide A, 327. C13H18Br2N6O5S – Nagelamide U, 64. C13H18Br3NO2 – Convolutamine A, 222. C13H18N2O3 – Penipacid A, 214. – Cladosin C, 594. – Cladosin Cmajor, 595. – Cladosin Cminor, 596. C13H19Br2NO2 – Convolutamine B, 223. C13H19NO – 3-Methyl-N- (2‘-phenylethyl)-butyramide, 150. C13H20N2O4 – Cladosin F, 597. C13H20N4O2 – Fuscusine, 62. C13H27N3O – Pulchranin B, 68.

C14 C14H12N2O2 – 1-Ethyl-β-carboline-3-carboxylic acid, 819. C14H13NO5S – Nitrosporeusine A, 622. – Nitrosporeusine B, 623. C14H13N3 – 3-((6-Methylpyrazin-2-yl)methyl)-1H-indole, 712. C14H14N4O – Aplysinopsin, 1008. – Isoplysin A, 1025. C14H15BrN4O – Aplicyanin B, 55. C14H15BrN4O2 – 6-Bromo-1′-hydroxy-1′,8-dihydroaplysinopsin, 946. – Trachycladindole B, 1033. C14H15BrN4O3 – Trachycladindole D, 1035. – Trachycladindole E, 1036. C14H15BrN4O4 – Trachycladindole F, 1037. C14H15NO2 – Penipaline C, 714. C14H16BrN3O2S – Eudistomin C, 829. – Eudistomin E, 831. C14H16BrN3OS – Eudistomin K, 837. – Eudistomin L, 838. C14H16Br2N2O2 – 5,6-Dibromo-L-hypaphorine, 955. C14H16I2N2O2 – Plakohypaphorine B, 978. – Plakohypaphorine C, 979. – Plakohypaphorine D, 980. C14H16N2O2 – 1,2,3,4-Tetrahydro-1,1-dimethyl-β-carboline -3β-carboxylic acid, 887. C14H16N3O1+ – Dysideanin B, 817. C14H17BrN2O2 – (+)-5-Bromohypaphorine, 947. C14H17Br2N3O4 – Ceratinine D, 323.

Index 2 Compound Molecular Formula Index

C14H18BrN3O – Tambjamine D, 437. – Tambjamine I, 442. C14H18N2O3 – Bohemamine, 624. C14H19NO6 – Nordomoic acid, 570. C14H19N3O – Tambjamine C, 436. C14H20N2O2 – Deepoxybohemamine, 626. C14H21Br3N2O – Convolutamine I, 8. C14H22Br2N2O – Purealidin G, 235. – Purealidin F, 301. C14H22Br2O2 – Motualevic acid E, 154. C14H22N2O4 – Cladosin G, 598. C14H25N – (2S,3E,5Z)-3,5,13-Tetradecatrien-2-amine, 5. C14H26N2O5 – Tenacibactin B, 45. C14H29N3O – Pulchranin A, 67. C14H31N2O2 – Neocomplanine B, 156. C15 C15H9BrN4O2 – Didemnimide B, 1014. C15H10BrN3O – Eudistomin A, 827. C15H10Br6N2O5 – Symphyocladin G, 43. C15H10N4O2 – Didemnimide A, 1013. C15H11NO6 – Coproverdine, 781. C15H11N3O – Eudistomin M, 839. C15H12BrN3 – Eudistomin G, 833. – Eudistomin H, 834. C15H12BrN3O – Eudistomidin A, 821. C15H12N3O – Eudistomin P, 842.

425

C15H13N3 – Eudistomin I, 835. C15H13N3O – Eudistomin Q, 843. C15H14BrN3O – Plakortamine D, 885. C15H15NO4 – Conioimide, 1086 C15H15N5O3 – Clathridine C, 1130 C15H16BrN3 – Plakortamine A, 882. C15H16BrN3O2S – Eudistomidin J, 826. C15H16BrN3OS – Eudistomidin C, 823. C15H16Br2N4O2 – Aplicyanin F, 58. C15H16Br2N4O4 – Purealidin N, 1158 C15H16N2O3Br2 – Amathaspiramide E, 543. C15H16N4O – N-3′-Methylaplysinopsin, 1030. C15H17BrN4O2 – Aplicyanin D, 56. – 6-Bromo-1′-methoxy-1′,8-dihydroaplysinopsin, 948. C15H17BrN4O3 – 5-BromoVerongamine, 1127 C15H17Br2N5O4 – Purealidin M, 1157 C15H18BrN3O6S2 – Psammaplin F, 291. C15H18N2O – 3-Oximido-ethyl-6-prenylindole, 977. C15H19BrN4O5S2 – Psammaplin E, 290. C15H19N – (–)-Herbindole A, 684. – (+)-Herbindole A, 685. – (1′′S,3′′S)-Trikentrin A, 720. – (1′′R,3′′S)-Trikentrin A, 721. C15H19NO – 3-(2-Hydroxyethyl)-6-prenylindole, 699. C15H19NO3 – 2-(1H-Indol-3-yl)ethyl-5-hydroxypentanoate 701.

426

Index 2 Compound Molecular Formula Index

C15H19NO4 – Barmumycin, 544. C15H20BrN3O – Tambjamine J, 443. C15H20BrN3O5S2 – Psammaplin D, 289. C15H20BrN5 – (+)-7-Bromotrypargine, 59. C15H20BrN5O5S2 – Psammaplin G, 292. C15H20Br3NO3 – Convolutamine E, 325. C15H20N4O4 – Herdmanine I, 691. C15H21Cl6NO3 – Dysidamide, 551. C15H21NO6 – Domoic acid, 550. – Isodomoic acid A, 556. – Isodomoic acid B, 557. – Isodomoic acid C, 558. – Isodomoic acid G, 559. – Isodomoic acid H, 560. C15H21N3O – Tambjamine K, 444. C15H21N3O3 – Herdmanine J, 692. C15H22Br2N6O5S – Mauritamide A, 487. C15H23N3 – Mirabilin B, 73. C15H25N3 – Isoptilocaulin, 72. – (+)-Ptilocaulin, 74. C15H27N5O5 – Rexostatine, 40. C15H28N2O2 – Caprolactin A, 200. – Caprolactin B, 201. C15H28N2O5 – Tenacibactin A, 44. C16 C16H8Br4N2 – 2,2′,5,5′-Tetrabromo-3,3′-bi-1H-indole, 774. C16H10N4O4 – Hyrtiocarboline, 858. C16H11BrN4O2 – Didemnimide D, 1016.

C16H12N2O3 – 2-(4-Hydroxybenzoyl)-4(5)-(4-hydroxyphenyl)1H-imidazole, 1135 C16H12N4O – Xestomanzamine A, 890. C16H12N4O2 – Didemnimide C, 1015. C16H13BrN4OS – Didemnoline C, 815. C16H13BrN4S – Didemnoline A, 813. C16H13N3O2 – Antipathine A, 778. C16H14N4O – Xestomanzamine B, 891. C16H14N4O5 – Herdmanine K, 693. – Herdmanine K, 1021. C16H14N4OS – Didemnoline D, 816. C16H14N4S – Didemnoline B, 814. C16H15BrN4O3 – Bunodosine 391, 1010. C16H15NO5 – Herdmanine L, 694. C16H15N5O4 – Clathridine A, 1129 C16H16N2O3 – Limazepine G, 176. C16H16N4 – Villagorgin A, 889. C16H16N4O3 – Hainanerectamine C, 854. – Hyrtioreticulin B, 863. C16H16N6O – Tiruchanduramine, 888. C16H17NO – 6-(1H-Indol-3-yl)-5-methyl-3,5-heptadien2-one, 705. C16H18BrN3 – Eudistalbin A, 820. C16H18BrN3OS – N14-Methyleudistomidin C, 871. C16H18BrN3O4S – Eudistomin F, 832. C16H18N4O – N-3′-Ethylaplysinopsin, 1018.

Index 2 Compound Molecular Formula Index

C16H19BrN2 – Pibocine A, 1116 C16H19BrN2O – Arborescidine D, 808. C16H19BrN4O2 – 6-Bromo-1′-ethoxy-1′,8-dihydroaplysinopsin, 1009. C16H19N3O5 – Aplaminal, 183. C16H19N5O5 – (–)-(R)-Leptoclinidamine B, 975. C16H20BrN52+ – Opacaline A, 876. C16H20BrN5O2+ – Opacaline B, 877. C16H20Br2N2O3 – Amathaspiramide A, 542. C16H20Br3N2O21+ – Amathamide C, 540. – Amathamide H, 541. C16H20N2 – Costaclavine, 1099 C16H20N2O – FumigaclavineB, 1104 C16H21BrN2 – 6-Bromo-Nb-methyl-Na-prenyltryptamine, 949. – Deformylflustrabromine, 953. – Deformylflustrabromine B, 954. – Flustramine E, 984. C16H21BrN2O – Flustramine I, 986. C16H21N – (–)-Herbindole B, 686. – (+)-Herbindole B, 687. C16H22Cl3NO4 – Dysidine (1977), 553. C16H25Br2NO3 – Motualevic acid A, 151. C16H25NO3 – Penicillenol B1, 605. – Penicillenol B2, 606. C16H26Br2NO3 – Motualevic acid B, 152. C16H26Br2N2O2 – Motualevic acid C, 153. C16H27NO3 – Scalusamide A, 575.

C16H27NO4 – Penicillenol A1, 603. – Penicillenol A2, 604. C16H35N2O2 – Neocomplanine A, 155. C17 C17H10Br4N2O – (+)-2,3ʹ,5,5ʹ-Tetrabromo-7ʹ-methoxy-3, 4ʹ-bi- 1H-indole, 775. C17H10N2O C17H10O5S C17H11Br3N2O – Rivularin D1, 770. C17H13N3O2 – Circumdatin F, 172. C17H13N3O3 – Circumdatin C, 171. – Circumdatin G, 173. C17H13N3O4 – Circumdatin I, 174. C17H14N2 – 3,3′-Methylenebisindole, 761. C17H15Br3N2O4 – Hemibastadin 2, 280. C17H15Br3N2O7S – 1-O-Sulfohemibastadin 2, 317. C17H15N3O4 – 2-Hydroxycircumdatin C, 175. C17H16BrN3O2 – Eudistomin B, 828. C17H16Br2N2O7S – 1-O-Sulfohemibastadin 1, 316. C17H16Br2N4O2 – Ceratamine A, 205. C17H20Br2ClN9O2 – 4,5-Dibromopalauamine, 472. – 2,3-Dibromostyloguanidine, 475. C17H20N2O2 – Penipaline A, 880. C17H21BrClN9O2 – 4-Bromopalauamine, 456. – 3-Bromostyloguanidine, 457. C17H21BrN2O – Pibocine B, 1117 C17H21Br4N5O2 – Pseudoceratidine, 39.

427

428

Index 2 Compound Molecular Formula Index

C17H21N – Iso-trans-trikentrin B, 707. – cis-Trikentrin B 722. C17H22BrN7O – Phidianidine A, 36. C17H22Br2N6O3 – Purealidin A, 1154 C17H22Br3N3O – Alternatamide B, 941. C17H22ClN9O2 – Palauamine, 508. – Styloguanidine, 515. C17H22Cl6N2O4 – Dysideapyrrolidone, 552. C17H22N2O – Brocaeloid C, 809. C17H23Br2N3O – Alternatamide C, 942. – Alternatamide D, 943. C17H23Cl2NO – Kimbeamide A, 145. C17H23NO2 – Lorneamide A, 147. C17H23N3O2 – Indolactam V, 1039. C17H23N3O5 – Cathestatin A, 177. C17H23N3O6 – Cathestatin B, 178. C17H23N7O – Phidianidine B, 37. C17H25BrN4O22+ – Didemnidine B, 11. C17H25Br2N3O2 – Ianthelliformisamine B, 23. – Tokaradine C, 48. C17H25NO3 – Cyclizidine, 629. C17H26Br2N6O3 – Oceanapia Bromotyrosine alkaloid, 35. C17H26N4O22+ – Didemnidine A, 10. C17H28I2N2O – Turbotoxin B, 237. C17H30I2N2O2+ – Turbotoxin A, 236. C17H30N2O6 – Bengamide E, 188. – Isobengamide E, 207.

C17H30N2O7 – Bengamide Y, 196. C18 C18H9Br3N2O2 – Eudistomin Y6, 850. – Eudistomin Y7, 851. C18H10BrN2O1+ – 3-Bromofascaplysin, 810. C18H10Br2N2O2 – Eudistomin Y4, 848. – Eudistomin Y5, 849. C18H10Cl4N2O3 – Chlorizidine A, 625. C18H10N2O3 – 6-Oxofascaplysin, 878. C18H11BrN2O2 – Eudistomin Y2, 846. – Eudistomin Y3, 847. C18H11N2O1+ – Fascaplysin, 852. C18H12Br4N2O2S2 – 3,3′-Bis(4,6-dibromo-2-methylsulfinyl)indole, 725. C18H12Br4N2OS2 – 3,3′-Bis(2′-methylsulfinyl-2-methylthio-4, 6,4′,6′-tetrabromo)indole, 727. C18H12N2O2 – Xanthocillin X, 334. – Eudistomin Y1, 845. C18H12N2O4 – Secofascaplysic acid, 886. C18H15Br2NO3 – Keronopsin B2, 418. C18H15Br2NO4 – Botryllamide G, 271. C18H15Br2NO6S – Keronopsin A2, 416. C18H16BrNO3 – Keronopsin B1, 417. C18H16BrNO6S – Keronopsin A1, 415. C18H16Br4N2O4 – JBIR 44, 282. C18H16N2O – Halichrome A, 743. – Metagenediindole A, 759. C18H17N4O2S1+ – Hyrtiomanzamine, 862.

Index 2 Compound Molecular Formula Index

C18H19N3O – Tambjamine F, 439. C18H19N4OS – Gesashidine A, 853. C18H21Br3N3O1+ – Kororamide A, 970. C18H22Br2IN3O2 – Agelanesin D, 338. C18H22Br3N3O2 – Agelanesin C, 337. C18H23BrIN3O2 – Agelanesin B, 336. C18H23BrN2O – Flustramine F, 985. C18H23Br2N3O2 – Agelanesin A, 335. C18H23N – (–)-Herbindole C, 688. – (+)-Herbindole C, 689. C18H24Br3N3O – Alternatamide A, 940. C18H25N3O6 – Cathestatin C, 7. C18H25N5O5 – Estatin A, 12. C18H25N5O6 – Estatin B, 13. C18H28ClNO – Janthielamide A, 143. C18H28N3O21+ – Clathriadic acid, 83. C18H29N – Villatamine A, 576. – Piclavine C, 632. C18H31N – Piclavine B, 631. C18H32N2O6 – Bengamide F, 189. C18H32N2O7 – Bengamide Z, 197. C18H32N4O6 – Bisucaberin, 198. C18H33N – Villatamine B, 577. C18H35N2O21+ – Complanine, 131. C18H39N3 – Motuporamine A, 31.

C19 C19H11N3O2 – Hyrtimomine A, 746. C19H12Br2N4 – Nortopsentin A, 762. C19H13BrN4 – Nortopsentin B, 763. – Nortopsentin C, 764. C19H13N3 – Eudistomin U, 844. C19H13N3O – Iheyamine A, 752. C19H14Br2N2O5S – Echinosulfonic acid C 1‘‘-deoxy, 742. C19H14Br2N2O6S – Echinosulfonic acid C, 741. C19H15N2O21+ – 1-Deoxysecofascaplysin A, 812. C19H15N3 – Isoeudistomin U, 865. C19H18BrN3O4 – Clionamide, 951. C19H18BrNO4 – Botryllamide D, 270. C19H18N4O2 – 4-Methoxy-5-[(3-methoxy-5-pyrrol-2-yl2H-pyrrol-2-ylidene)methyl]-2,2′bipyrrole, 427. C19H19NO5 – Iotrochamide A, 180. C19H19N3O2 – Neoechinulin B, 998. C19H20Br2N2O2 – Bromochelonin B, 944. C19H20Br2N4O2 – Kottamide D, 974. C19H21BrN2O2 – Chelonin B, 950. C19H21N3O2 – Neoechinulin A, 997. C19H24N2O2 – Penipaline B, 881. C19H25ClN2O3 – Nitropyrrolin C, 390. C19H25NO5 – Streptosetin A, 616. C19H28N2O3 – Nitropyrrolin B‡, 389. – Nitropyrrolin D, 391.

429

430

Index 2 Compound Molecular Formula Index

C19H29NO3 – 5-Dodecenyl-4-amino-3-hydroxybenzoate, 211. C19H30N2O4 – Nitropyrrolin A, 388. C19H30N2O6 – Heronapyrrole C, 348. C19H31ClN2O5 – Nitropyrrolin E, 392. C19H31ClO7 – Calcareous sponge Leucetta Acetylenic Alkaloid, 1. C19H32N2O4 – JBIR 66, 144. C19H32N2O6 – Heronapyrrole B, 347. C19H33NO – Mycalazal 14, 356. C19H33NO2S – Ircinamine, 555. C19H36N31+ – Merobatzelladine B, 94. C19H41N3 – Motuporamine B, 32. C20 C20H11Cl4N3 – Lynamicin C, 756. C20H11N3O2 – Arcyriaflavin A, 790. C20H12Br2N2 – 7-Bromo-1-(6-bromo-1H-indol-3-yl)-9Hcarbazole, 779. C20H13BrN4O – Isobromodeoxytopsentin, 1023. – Bromodeoxytopsentin, 1126 C20H13BrN4O2 – Topsentin B2, 777. – Isobromotopsentin, 1024. C20H13N3O – Staurosporine aglycone, 804. C20H13N3O4 – Hyrtioerectine D, 859. C20H13N3O5 – Hyrtimomine F, 749. C20H14BrN2O31+ – 3-Bromohomofascaplysin A, 811. C20H14N2O4 – Racemosine A, 766.

C20H14N4O2 – Hyrtinadine A, 751. – Topsentin, 776. C20H14N4O3 – Hyrtioerectine F, 861. C20H15BrN4O – Dihydrodeoxybromotopsentin, 736. C20H16Br2N2O6S – Echinosulfonic acid B, 740. C20H16N2O6 – Hyrtimomine G, 750. C20H19ClN2O8 – Trichodermamide B, 169. C20H19N3O3 – Kealiinine A, 1139 C20H19N3O4 – Leucettamine A, 1141 C20H20Br2N4 – (±)-Gelliusine F, 964. C20H20Br2N4O2 – Dendridine A, 735. C20H20N2O3 – α-Cyclopiazonic acid, 1046 – Iso-α-cyclopiazonic acid, 1057 C20H20N2O9 – Trichodermamide A, 168. C20H21BrN4O – (±)-Gelliusine D, 962. – (±)-Gelliusine E, 963. C20H21Br2N7O4 – Nakamuric acid, 504. C20H22Br3N3O4 – Purpuramine F, 305. C20H23Br2N3O3 – Purpuramine D, 303. – Purpuramine A, 330. C20H23N3O – Cycloprodigiosin hydrochloride, 526. C20H24BrN3O3 – Purpuramine B, 331. C20H25N3O – Prodigiosin, 530. C20H29Br2N6O31+ – Purealidin E, 1156 C20H32Br2N4O2 – Ianthelliformisamine A, 22. C20H34N2O6 – Heronapyrrole A, 346.

Index 2 Compound Molecular Formula Index

C20H35NO – 5-(13-Methyltetradecyl)-1H-pyrrole-2-carboxaldehyde, 353. – 5-Pentadecyl-1H-pyrrole-2-carboxaldehyde, 395. C20H41N3 – Motuporamine C, 33. C21 C21H13BrN4O2 – Rhopaladin C, 769. C21H14N4O3 – Rhopaladin B, 768. C21H15N3O4 – Terremide B, 167. – Hyrtioerectine E, 860. C21H17N2O21+ – Homofascaplysin A, 856. C21H17N3O – Chondriamide A, 731. – Chondriamide C, 733. C21H17N3O2 – Chondriamide B, 732. C21H17N3O5 – Terremide A, 166. C21H18Br2N2O6S – Echinosulfonic acid A, 739. C21H19BrN2O4 – Iotrochamide B, 181. C21H19N5O4 – Isonaamidine D, 1137 C21H21ClN2O – Hapalindolinone A, 1055 C21H21Cl2N3O3 – N-{1-[4-(Acetylamino)phenyl]-3-hydroxy-1-(1Hindol-3-yl)propan-2-yl}-2,2-dichloroacetamide, 669. C21H22N2O – Hapalindolinone B, 1056 C21H22N2O3 – 3-(3-(2-Hydroxyethyl)-(1H-indol-2-yl)-3-(1Hindol-3-yl)propane-1,2-diol), 744. C21H23Br2N7O4 – Nakamuric acid methyl ester, 505. C21H23Br3N2O3 – Aplysamine 6, 221. C21H23Br4N3O4 – Aplysamine 4, 242.

431

C21H23ClN2 – Hapalindole A, 1047 – 12-epi-Hapalindole E, 1049 – 12-epi-Hapalindole G, 1050 C21H23ClN2OS – Hapalindole T, 1054 C21H23NO8 – 15-Norpseurotin A, 571. C21H24BrN3 – Eudistomidin B, 822. – Eudistomidin G, 825. C21H24Br2N4O2 – Kottamide A, 971. C21H24Br3N3O4 – Aplysamine 3, 241. – 16-Debromoaplysamine 4, 275. – Purpuramine G, 306. C21H24N2 – 12-epi-Hapalindole C, 1048 – 12-epi-Hapalindole H, 1051 – 12-epi-Hapalindole J, 1052 – 12-epi-Hapalindole Q, 1053 C21H25BrN4O2 – Kottamide B, 972. – Kottamide C, 973. C21H25Br2N3O3 – Purpuramine E, 304. C21H27NO6 – Epolactaene, 554. C21H27N3O2 – Brevicompanine C, 991. C21H28N2 – 2-(3,3-Dimethylprop-1-ene)-costaclavine, 1102 – 2-(3,3-Dimethylprop-1-ene)-epi-costaclavine, 1103 C21H29BrN2 – Flustramine A, 982. – Flustramine B, 983. C21H29BrN2O – Flustramine L, 987. C21H31NO3 – 2,7-Tetradecadienyl-4-amino-3hydroxybenzoate, 216. C21H33NO2 – N-[2-(4-Hydroxyphenyl)ethyl]-3-methyl2-dodecenamide, 232. C21H33NO3 – 7Z-Tetradecenyl-4-amino-3-hydroxybenzoate, 217.

432

Index 2 Compound Molecular Formula Index

C21H34N2O – Mycalenitrile 13, 386. C21H35Cl2NO2 – Grenadamide C, 139. C21H35NO – Mycalazal 16, 358. – Mycalazal 17, 359. C21H35NO2 – Malonganenone K, 148. C21H36ClNO2 – Grenadamide B, 138. C21H37NO – 5-Hexadecyl-1H-pyrrole-2-carboxaldehyde, 349. – 5-(14-Methylpentadecyl)-1H-pyrrole-2carboxaldehyde, 352. C22 C22H11BrCl4N2O4 – Marinopyrrole B, 424. C22H11Cl3N2O4 – (±)-Marinopyrrole F, 426. C22H11Cl5N2O4 – (–)-Marinopyrrole C, 425. C22H12Cl4N2O4 – Marinopyrrole A, 423. C22H14Cl3N3O2 – Lynamicin B, 755. C22H14N2O2 – Racemosine B, 767. C22H15ClN2O2 – Caulerchlorin, 728. – Chloro-bisindole, 730. C22H15Cl2N3O2 – Lynamicin A, 754. – Spiroindimicin C, 772. C22H16N4O3 – Gliocladine C, 994. C22H19N3O2 – Marinacarboline C, 869. C22H19N3O3 – Marinacarboline B, 868. C22H20Br4N10O2 – Nagelamide C, 494. C22H20Br4N10O3 – Mauritiamine, 488. C22H21Br4ClN10O3 – Carteramine A, 458.

C22H21NO7 – Cephalimysin C, 203. – Cephalimysin D, 204. C22H22Br3ClN10O3 – Konbuacidin A, 486. C22H22Br4N10O2 – 2,2‘-Dibromoageliferin, 471. – Dibromosceptrine, 474. – Nagelamide A, 492. – Nagelamide G, 498. C22H22Br4N10O3 – Nagelamide B, 493. C22H22N2O2 – Arsindoline B, 724. C22H22N2O4 – 2-(2-(3-Hydroxy-1-(1H-indol-3-yl)-2methoxypropyl)-1H-indol-3-yl) acetic acid, 745. C22H23Br2N4O9S31– Sodium salt of psammaplin A sulfate, 311. C22H23Br3N4O6S2 – Bromopsammaplin A, 272. C22H23Br3N10O2 – 2-Bromoageliferin, 454. – Nagelamide F, 497. C22H23Br4ClN10O4 – Axinellamine A, 450. – Axinellamine B, 451. C22H23N5O2 – Roquefortine C, 1003. C22H24BrN10O2 – Debromosceptrine, 469. C22H24Br2N4O6S2 – Psammaplin A, 287. C22H24Br2N4S – Citorellamine, 734. C22H24Br2N10O2 – Ageliferin, 449. – Nagelamide E, 496. – Sceptrine, 509. C22H24Br2N10O3 – Oxysceptrine, 507. C22H24Br3ClN10O4 – Nagelamide O, 500. C22H24Br3N3O4 – Purpurealidin B, 309. C22H24Br4N10O2 – Nagelamide D, 495.

Index 2 Compound Molecular Formula Index

C22H25BrN10O3 – Debromooxysceptrine, 468. C22H25Br2N6O31+ – Purealidin D, 1155 C22H25NO6 – Cephalimysin A, 202. C22H25NO8 – Pseurotin A, 573. C22H26Br3N3O4 – Purpuramine I, 307. C22H27N7O – Cypridina Luciferin, 60. C22H28BrN5O6 – Herdmanine E, 690. C22H29N3O2 – Brevicompanine A, 989. – Brevicompanine B, 990. C22H31NO4 – Equisetin, 600. C22H31N3O2 – 13-N-Demethyl-methylpendolmycin, 1101 C22H33ClO4 – JBIR 102, 630. C22H33NO – Mycalazal 19, 361. C22H33NO4 – Mariline B, 1091 C22H33NO5 – Xylarisin, 668. C22H35NO – Mycalazal 18, 360. C22H35NO3 – N-[2-(4-Hydroxy-3-methoxyphenyl)ethyl]-3methyl-2-dodecenamide, 230. – N-[2-(3-Hydroxy-4-methoxyphenyl)ethyl]-3methyl-2-dodecenamide, 231. C22H35N3O – Antibiotic BE 18591, 413. C22H36ClNO2 – Pitiamide A, 157. C22H37NO – Mycalazal 15, 357. C22H37N4O1+ – Stellettazole D, 1160 C22H43NO3 – Serinolamide B, 161.

C23 C23H13N5O4 – Naamidine A, 1149 C23H17Br2N7O – Nortopsentin D, 765. C23H17Cl2N3O2 – Spiroindimicin B, 771. C23H18N2O – 7,7-Bis(3-indolyl)-p-cresol, 726. C23H21N3O3 – Marinacarboline A, 867. C23H23N3O3 – Isonaamidine C, 1136 C23H23N5O4 – Meleagrin, 1026. C23H24ClNO3 – Chloroxiamycin, 780. C23H25Br4ClN10O4 – Axinellamine C, 452. C23H25NO3 – Xiamycin, 786. C23H25NO4 – Oxiamycin, 785. – Xiamycin B, 788. C23H25N5O3 – Roquefortine F, 1004. – Roquefortine I, 1007. C23H28Br3N3O4 – Aplysamine 2, 240. C23H28Br3N3O5 – Aplysamine 7, 244. – Purpuramine J, 308. C23H28Br4N4O4 – Purealidin C, 300. C23H29I2NO2 – Hicksoane C, 697. C23H29N3 – Manzamine C, 866. C23H30Br3N3O3 – Suberedamine A, 312. C23H30INO2 – Hicksoane A, 695. – Hicksoane B, 696. C23H30N2O2 – Fumigaclavine C, 1105 C23H31NO4 – Stachyflin, 1095

433

434

Index 2 Compound Molecular Formula Index

C23H33NO3S – Dysidine (2001), 212. C23H34N2O – Granulatamide A, 681. C23H37NO2 – Hermitamide A, 228. C23H38N2O – Mycalenitrile 1, 375. C23H41NO2 – Mycalazol 7, 369. C23H42N31+ – Merobatzelladine A, 93. C23H42N4O8 – Tenacibactin C, 46. C23H45NO3 – Serinolamide A, 160. C23H45N3O – N′,N′′,N′′-Trimethyl-N-(3-methyl-2Z,4Edodecadienoyl)spermidine, 49. – N′,N′,N′-Trimethyl-N-(3-methyl-2,4dodecadienoyl)spermidine, 50. C23H47NO2S – Sinulasulfoxide, 163. C23H47NO3S – Sinulasulfone, 162. C23H47N3O – N′,N′′,N′′-Trimethyl-N-(3-methyl-2Zdodecenoyl)spermidine, 52. – N′,N′,N′-Trimethyl-N-(3-methyl-2E-dodecenoyl) spermidine, 53. C23H49N3O – N′,N′,N′-Trimethyl-N-(3-methyldodecanoyl) spermidine, 51. C23H49N3O3 – Fromia monilis Alkaloid, 21. C24 C24H17Cl2N3O4 – Lynamicin D, 757. C24H17N3O – 2,2-Di-3-indolyl-3-indolone, 737. C24H18ClN3O4 – Lynamicin E, 758. C24H18N2O4 – Caulerpin, 729. C24H19NO5 – Lamellarin R, 351. C24H20Cl2N2O4 – Tjipanazole A1, 806.

– Tjipanazole A2, 807. C24H20N4O2 – Marinacarboline D, 870. C24H21Cl2N3 – Indimicin B, 797. C24H21N3O4 – Cyanogramide, 1100 C24H25Br4N11O5S – Nagelamide H, 499. C24H25N5O5 – Isonaamidine E, 1138 C24H27NO3 – Xiamycin A methyl ester, 787. C24H28Br4N11O5S1+ – Nagelamide Y, 503. C24H28Br4N11O6S1+ – Nagelamide X, 502. C24H31NO4 – Aspochalasin A, 634. C24H31N3O3 – Brevicompanine H, 993. C24H32Br3N3O3 – Suberedamine B, 313. C24H34N2O – Granulatamide B, 682. C24H34N4O3 – JBIR 81, 967. C24H35Br2NO4 – Convolutamide A, 545. C24H35Cl2NO5 – Gymnastatin Q, 140. C24H35NO4 – Aspochalasin D, 635. – Aspochalasin J, 638. C24H35NO5 – Aspochalasin H, 636. – Aspochalasin I, 637. C24H37NO – Mycalazal 20, 362. C24H39NO2 – N- (2-Phenylethyl)-9oxohexadecacarboxamide, 234. C24H40N2O – Mycalenitrile 14, 387. C24H41NO2 – N- (2-Phenylethyl)-9hydroxyhexadecacarboxamide, 233. – Mycalazol 4, 366.

Index 2 Compound Molecular Formula Index

C24H41N2O1+ – Stellettamide B, 633. C24H43NO2 – Mycalazol 11, 373. C24H48NO41+ – Homopahutoxin, 2. C25 C25H16INO5 – Lukianol B, 420. C25H17NO5 – Lukianol A, 419. C25H17NO8 – Lamellarin A4, 401. C25H19Cl2N3O4 – Spiroindimicin D, 773. C25H21BrN7O21+ – Dragmacidin D, 738. C25H23N3O3 – Iheyamine B, 753. C25H24N6O5 – Leucettamidine, 1140 C25H25N5O7 – Naamidine F, 1150 C25H26BrN5O13 – Surugatoxin, 1123 C25H26Br2N3O31+ – Purpuramine C, 302. C25H27Br4ClN8O52+ – 3-O-Methylmassadine chloride, 489. C25H30N4O5 – Monodontamide A, 26. C25H31N3O5 – Moiramide B, 621. C25H32N2 – Ambiguine H isonitrile, 1044. C25H32N4O6 – Monodontamide C, 28. C25H33NO5 – Cytochalasin Z11, 647. C25H33N3O3 – Brevicompanine E, 992. C25H35NO4 – Phomasetin, 607. C25H35NO5 – Cytochalasin Z12, 648. C25H35NO6 – Zopfiellamide A, 617.

435

C25H35N3O2 – Marineosin A, 421. – Marineosin B, 422. C25H38N2O – Mycalenitrile 6, 379. C25H38N2O2 – Hermitamide B, 965. C25H39NO5 – Korormicin A, 146. C25H40N2O – Mycalenitrile 8, 381. C25H42N2O – 5-(19-Cyanononadecyl)-1H-pyrrole-2carboxaldehyde, 340. – Mycalenitrile 7, 380. C25H46N6O2 – Batzelladine D, 77. C25H49NO4 – N-(1ʹR-Hydroxymethyl-2-methoxyethyl)-7Smethoxy-4E-eicosenamide, 141. C25H51N3O – N’,N’’,N’’-Trimethyl-N-(5-methyl-3tetradecenoyl)spermidine, 54. C26 C26H17NO8 – Lamellarin A5, 402. C26H19N3O – Metagenetriindole A, 760. C26H19NO8 – Lamellarin β, 412. C26H24BrN8O21+ – Dictazole A, 476. C26H24N4O5 – Tolyporphin G, 537. – Tolyporphin H, 538. C26H27N3O4 – Notoamide I, 1114 C26H28ClN3O5 – 5-Chlorosclerotiamide, 1098 C26H29N3O3 – Stephacidin A, 1121 C26H29N3O4 – 6-epi-Avrainvillamide, 1097 – N-Hydroxy-6-epi-stephacidin A, 1108 – Isonotoamide B, 1109 – (–)-Notoamide B, 1113 C26H29N3O5 – Notoamide A, 1112

436

Index 2 Compound Molecular Formula Index

– (–)-Sclerotiamide, 1118 C26H30N2O2 – Ambiguine I isonitrile, 1045. C26H30N6O5 – Pyronaamidine 9-N-methylimine, 1159 C26H31N5O4 – Monodontamide E, 30. C26H32N4O7 – Monodontamide B, 27. C26H33Br4N3O3 – Psammaplysene B, 295. C26H35NO5 – Stachybotrin D, 1094 C26H36N2O – Nakadomarin A, 927. C26H36N2O5 – Ypaoamide, 578. C26H37Br2NO4 – Convolutamide B, 546. C26H37NO6 – Zopfiellamide B, 618. C26H37N3O2 – N13-Demethylteleocidin A1, 1038. C26H38N2O2 – Ircinal A, 908. C26H40BrNO3 – Aplaminone, 220. C26H40BrNO4 – Neoaplaminone, 284. C26H40BrNO7S – Neoaplaminone sulfate, 285. C26H40N2O – Xestocyclamine A, 935. C26H40N2O2 – Ircinal B, 909. – Ircinol A, 910. C26H41NO – Mycalazal 3, 355. C26H41NO2 – Mycalazol 2, 364. C26H43NO2 – Mycalazol 6, 368. C26H44N2O – Mycalenitrile 2, 376. C26H45NO2 – Mycalazol 10, 372. C26H48N4O9 – Synechobactin A, 165.

C26H49NOS – Ircinamine B, 350. C26H49N5O2 – Acarnidine C, 6. C27 C27H21NO8 – Lamellarin A1, 398. C27H22N4O6 – 7-Oxo-8,9-dihydroxy-4′-Ndemethylstaurosporine, 799. C27H23Br2N5 – Plakortamine C, 884. C27H26BrN3O8 – Tetraacetylclionamide, 981. C27H28BrN7O5 – Halocyamine A, 1019. C27H31N5O5 – Monodontamide D, 29. C27H33NO3 – Dehydroxypaxilline, 1061 C27H33NO4 – Paxilline, 1077 C27H33NO5 – 4a-Demethylpaspaline-3,4,4a-triol, 1063 – 2′-Hydroxypaxilline, 1069 C27H33N3O3 – Mangrovamide C, 1110 C27H33N3O5 – Andrimide, 619. C27H34N2O5 – Cylindramide, 599. C27H35Br4N3O3 – Psammaplysene A, 294. C27H35NO2 – 3-Deoxo-4b-deoxypaxilline, 1064 C27H36BrClN2O4 – Jamaicamide A, 561. C27H37ClN2O4 – Jamaicamide B, 562. C27H39ClN2O4 – Jamaicamide C, 563. C27H39N3O2 – Lyngbyatoxin A, 1041. C27H39N3O3 – JBIR 31, 1040. – Lyngbyatoxin B, 1042. – Lyngbyatoxin C, 1043.

Index 2 Compound Molecular Formula Index

C27H41N21+ – Zamamiphidin A, 939. C27H42N4O3 – Malonganenone B, 1146 – Malonganenone F, 1147 – Malonganenone G, 1148 C27H44N2O – Mycalenitrile 9, 382. – Mycalenitrile 11, 384. C27H46N6O2 – Batzelladine E, 78. C27H51NO5 – N-(1-Acetoxymethyl-2-methoxyethyl)-7methoxy-4-eicosenamide, 125. C28 C28H21NO8 – Lamellarin D, 406. C28H22N4O4 – Antibiotic ZHD-0501, 789. C28H22N5O3S1+ – Hyrtimomine D, 747. C28H23NO8 – Lamellarin A6, 403. C28H23NO9 – Lamellarin A2, 399. C28H23N3O5 – Streptocarbazole A, 805. C28H24N4O5 – 7-Oxo-2-hydroxystaurosporine, 800. – 7-Oxo-3-hydroxystaurosporine, 801. C28H24N4O7 – 7-Oxo-3,8,9-trihydroxystaurosporine, 802. C28H25BrN4O7 – Celenamide E, 179. C28H26N4O3 – Staurosporine, 803. C28H26N4O4 – 11-Hydroxystaurosporine, 795. – 5ʹ-Hydroxystaurosporine, 796. C28H26N4O6 – Tolyporphin I, 539. C28H28N8O2 – Tubastrindole B, 520. C28H28N8O3 – Cycloaplysinopsin C, 465. C28H31Br4N4O41+ – Tokaradine A, 319. – Tokaradine B, 320.

437

C28H33NO5 – Cytochalasin Z16, 649. – Cytochalasin Z17, 650. – Rosellichalasin, 667. C28H33NO7 – Cytochalasin E, 641. – Cytochalasin K, 642. C28H33N5O3 – Roquefortine H, 1006. C28H35NO4 – 7-Deoxycytochalasin Z7, 657. C28H35NO5 – Cytochalasin Z7, 644. – Cytochalasin Z8, 645. – Cytochalasin Z9, 646. – 21-Odeacetylcytochalasin Q, 658. C28H37Br4N3O3 – Psammaplysene D, 297. C28H37NO – Antibiotic JBIR 03, 1059 C28H37NO4 – 4a-Demethylpaspaline-4a-carboxylic acid, 1062 C28H38Br3N3O3 – Psammaplysene C, 296. C28H39NO – Emindole DA, 1066 – Emindole SB, 1067 C28H39NO2 – Paspaline, 1075 C28H41Br2NO4 – Convolutamide D, 547. C28H41NO2 – (6S,7R,10E,14E)-16-(1H-Indol-3-yl)-2,6,10,14tetramethylhexadeca-2,10,14-triene-6, 7-diol, 1072 C28H43Br2NO4 – Convolutamide E, 548. C28H43NO2 – Mycalazol 3, 365. C28H45NO2 – Mycalazol 8, 370. C28H46N2O – Mycalenitrile 12, 385. C28H47NO2 – Mycalazol 12, 374. C28H48N2O12 – Bengamide C, 186.

438

Index 2 Compound Molecular Formula Index

C28H54N6O8 – Tenacibactin D, 47. C29 C29H22N5O5S1+ – Hyrtimomine E, 748. C29H23NO9 – Lamellarin M, 410. C29H23NO11S – Lamellarin α 20-sulfate, 411. C29H25NO8 – Lamellarin A3, 400. – Lamellarin J, 408. C29H25NO9 – Lamellarin K, 409. C29H25N5O3 – Fradcarbazole C, 794. C29H26Br6N4O11 – Agelorin A, 238. – Agelorin B, 239. C29H27N5O3S – Fradcarbazole B, 793. C29H27N5O4 – N-Carboxamido-staurosporine, 791. C29H28N4O4 – 4ʹ-N-Methyl-5ʹ-hydroxystaurosporine, 798. C29H30N4O3 – Norcardioazine A, 999. C29H32BrN7O6 – Halocyamine B, 1020. C29H35N5O4 – Roquefortine G, 1005. C29H37NO3 – Deoxaphomin C, 655. C29H37NO5 – Cytochalasin B2, 640. C29H37NO8 – Cytochalasin Z19, 652. C29H38N2O6 – Alteramide A, 582. C29H39NO3 – Heronamide C, 206. C29H40I4N4O4 – N,N’-(1,5-Pentanediyl)bis[3-(3,5-diiodo-4methoxyphenyl)-2-dimethylamino-propanamide], 286. C29H41I3N4O4 – 3-(3,5-Diiodo-4-methoxyphenyl)-3ʹ-(3-iodo -4-methoxyphenyl)-N,N’-(1,5-pentanediyl)

bis(2-dimethylaminopropanamide), 278. C29H41NO2 – 27-O-Methylasporyzine C, 1074 C29H42N4O3 – JBIR 82, 968. C29H43N3O7 – Methylpendolmycin-14-O-α-glucoside, 1111 C29H46N2O – Mycalenitrile 4, 377. – Mycalenitrile 5, 378. C29H48N2O – Mycalenitrile 10, 383. C29H50N2O2 – Bengamide D, 187. C29H51N6O21+ – Dihomodehydrobatzelladine C, 88. C30 C30H25NO9 – Lamellarin B, 404. C30H27NO9 – Lamellarin C, 405. C30H27NO10 – Lamellarin A, 397. C30H30Br2N6O – (±)-Gelliusine A, 959. – (±)-Gelliusine B, 960. – (±)-Gelliusine C, 961. C30H32N4O9 – Nigribactin, 34. C30H36Br2N6O4 – Eusynstyelamide D, 18. C30H37NO5 – 18-Deoxycytochalasin Q, 656. C30H37NO6 – Cytochalasin Q, 643. C30H38Br2N8O4 – Eusynstyelamide E, 19. – Eusynstyelamide F, 20. C30H38Br4N4O4 – Ianthelliformisamine C, 24. C30H40N2O5 – Aburatubolactam A, 579. – Aburatubolactam C, 581. C30H40N2O6 – Aburatubolactam B, 580. C30H43NO2 – Mycalazol 1, 363.

Index 2 Compound Molecular Formula Index

C30H45Br2NO4 – Convolutamide F, 549. C30H45NO – Mycalazal 2, 354. C30H45NO2 – Mycalazol 5, 367. C30H47NO2 – Mycalazol 9, 371. C30H54N2O8 – Bengamide G, 190. C31 C31H28Br6N4O11 – 11-Ketofistularin 3, 283. C31H29NO9 – Lamellarin I, 407. C31H30Br6N4O10 – 11-Deoxyfistularin 3, 276. C31H30Br6N4O11 – Isofistularin 3, 281. C31H34N4O4 – Bonellin, 523. C31H35Cl3N2O9 – Rubroside H, 615. C31H41N5O6 – Namalide, 182. C31H43NO9 – Cytochalasin Z18, 651. C31H44ClN3O7 – PM050489, 158. C31H45N3O7 – PM060184, 159. C31H46N4O4 – Milnamide A, 875. C31H48Br2N6O4 – Lipopurealin A, 1143 C31H56N2O7 – Bengamide P, 194. C31H56N2O8 – Bengamide A, 184. – Bengamide N, 192. C32 C32H34N4O4 – Corallistin A, 525. C32H34N4O7 – Tolyporphin F, 536.

439

C32H35N3O3 – Penochalasin A, 659. – Penochalasin B, 660. – Penochalasin C, 661. C32H36N2O5 – Chaetoglobosin A, 639. C32H37N3O3 – Penochalasin D, 662. C32H37N5O5 – Meleagrin D, 1028. C32H38N2O4 – Cytoglobosin D, 654. – Penochalasin G, 665. C32H38N2O5 – Cytoglobosin C, 653. – Penochalasin E, 663. – Penochalasin F, 664. – Penochalasin H, 666. C32H39NO4 – Paspalitrem A, 1076 C32H39N5O6 – Meleagrin E, 1029. C32H40Br2N10O4 – Eusynstyelamide A, 14. – Eusynstyelamide B, 15. – ent-Eusynstyelamide B, 16. – Eusynstyelamide C, 17. C32H41NO4 – 21-Isopentenylpaxilline, 1073 C32H44MgN2O8 – Magnesidin, 602. C32H48Br2N8O10S4 – Diguanidium salt of psammaplin A sulfate, 277. C32H50Br2N6O4 – Lipopurealin B, 1144 C32H58N2O7 – Bengamide Q, 195. C32H58N2O8 – Bengamide B, 185. – Bengamide O, 193. C32H65NO12S – Turbinamide, 170. C33 C33H32N4O3 – Chlorophyllone a, 524.

440

Index 2 Compound Molecular Formula Index

C33H34N4O6 – Biliverdin, 522. C33H36N6O7S2 – Leptosin O, 995. – Leptosin P, 996. C33H38Cl2N2O9 – Rubroside G, 614. C33H43ClN2O15 – Aurantoside K, 593. C33H43NO5 – Mariline A1, 108. – Mariline A2, 109. C33H48Br4N6O5 – Pseudoceramine B, 38. C33H52Br2N6O4 – Lipopurealin C, 1145 C33H60N2O8 – Bengamide M, 191. C34 C34H24Br6N4O8 – Bastadin 22, 264. C34H24N2O8 – Dictyodendrin J, 414. C34H25Br5N4O8 – Bastadin 4, 248. – Bastadin 14, 258. C34H26Br4N4O11S – 15-O-Sulfonatobastadin 11, 318. C34H26Br4N4O12S – Bastadin 25, 266. C34H26Br4N4O14S2 – 15,34-Di-O-sulfatobastadin 7, 279. C34H26Br4N4O8 – Bastadin 7, 251. – Bastadin 11, 255. C34H26Br6N4O8 – Bastadin 6, 250. C34H26Br6N4O9 – Bastadin 24, 265. C34H27Br5N4O8 – Bastadin 5, 249. – Bastadin 15, 259. – Bastadin 16, 260. – (E,E)-Bastadin 19, 261. C34H27Br5N4O9 – Bastadin 8, 252.

– Bastadin 12, 256. C34H28Br4N4O11S – 34-Sulfobastadin 13, 315. C34H28Br4N4O13S – Bastadin 26, 267. C34H28Br4N4O8 – Bastadin 9‡, 253. – Bastadin 13, 257. – Bastadin 20, 262. C34H28Br4N4O9 – Bastadin 10, 254. C34H29Br3N4O8 – Bastadin 21, 263. C34H29Br5N4O8 – Bastadin 2, 246. C34H30Br4N4O11S – 10-O-Sulfatobastadin 3, 314. C34H30Br4N4O8 – Bastadin 1, 245. – Bastadin 3, 247. C34H36N4O8 – Tolyporphin E, 535. C34H40N4O6 – Aplysioviolin, 521. C34H47N3O3 – Acanthomanzamine A, 893. – Acanthomanzamine B, 894. C34H60N4O2 – Rhapsamine, 41. C34H66N4O2+ – Sinulamide, 42. C34H67NO6S – Flavochristamide A, 135. C34H69NO6S – Flavochristamide B, 136. C35 C35H36Br4N6O14 – Pseudoceratin A, 298. – Pseudoceratin B, 299. C35H36N4O5 – Pheophorbide a, 528. C35H44Cl2N2O15 – Aurantoside B, 588. C35H51NO5 – Emindole SB β-mannoside, 1068

Index 2 Compound Molecular Formula Index

C35H52N4O7 – 14-O-(N-Acetylglucosaminyl) teleocidin A, 1096 C35H57NO5 – Plakoridine A, 572. C35H58N6O2 – Batzelladine M, 81. C35H66N4O3 – Lipogrammistin A, 25. C36 C36H42N4O2 – 12,28-Oxamanzamine E, 930. C36H42N4O3 – 12,34-Oxa-6-hydroxymanzamine E, 929. C36H42N4O4 – Acantholactam, 892. C36H42N4O8 – Tolyporphin D, 534. C36H44N4O – Manzamine A, 917. C36H44N4O2 – 6-Deoxymanzamine X, 897. – 8-Hydroxymanzamine A, 903. – ent-8-Hydroxymanzamine A, 904. – Manzamine A N-oxide, 918. – Manzamine E, 921. C36H44N4O3 – 6-Hydroxymanzamine E, 907. – Keramamine B, 913. – ent-Manzamine F, 922. – Manzamine X, 926. C36H45N4O31+ – Pre-neo-kauluamine, 931. C36H46Cl2N2O15 – Aurantoside A, 587. C36H46N4O – 3,4-Dihydromanzamine A, 899. – Manzamine B, 919. – Manzamine J, 924. C36H46N4O2 – 3,4-Dihydro-6-hydroxy-10,11epoxymanzamine A, 898. – 3,4-Dihydromanzamine A N-oxide, 900. – 8-Hydroxymanzamine B, 906. C36H48N4O – Manzamine D, 920.

C36H48N4O2 – 3,4-Dihydromanzamine J N-oxide, 901. – 1,2,3,4-Tetrahydro-8-hydroxymanzamine A, 933. C36H50N4O – Manzamine H, 923. – Manzamine L, 925. – 1β,2,3,4-Tetrahydromanzamine B, 934. C36H50N4O2 – 10,11,15,16,32,33-Hexahydro-8hydroxymanzamine A, 902. C36H52Br3N3O5 – Aplysamine 5, 243. C37 C37H26N6O10S3 – Plectosphaeroic acid C, 1002. C37H43NO6 – Shearinine G, 1085 C37H44BrNO5 – 6-Bromopenitrem B, 1060 C37H44ClNO7 – 19-Hydroxypenitrem A, 1070 C37H44N4O2 – 12,28-Oxa-8-hydroxymanzamine A, 928. C37H45NO5 – Shearinine A, 1078 C37H45NO6 – 22α-Shearinine D, 1081 – Shearinine E (Smetanina, 2007), 1082 – Shearinine F (Smetanina, 2007), 1084 C37H45NO7 – 19-Hydroxypenitrem E, 1071 C37H46Cl2N2O15 – Aurantoside C, 589. – Aurantoside D, 590. C37H46N4O – Acanthomanzamine D, 895. C37H47NO5 – Shearinine B, 1079 C37H47NO7 – Shearinine C, 1080 C37H47N4O2 – 6-Hydroxymanzamine A, 905. C37H49NO3 – 9,10-Diisopentenylpaxilline, 1065

441

442

Index 2 Compound Molecular Formula Index

C37H50N4O2 – 1,2,3,4-Tetrahydro-2-N-methyl-8hydroxymanzamine A, 932. C37H52N4O2 – Maeganedin A, 914. C37H64N6O2 – Batzelladine F, 79. C38 C38H44N4O9 – Tolyporphin B, 532. – Tolyporphin C, 533. C38H47NO6 – Shearinine E (Xu, 2007), 1083 C38H48Cl2N2O15 – Aurantoside E, 591. C38H48N4O – Acanthomanzamine E, 896. C38H62N9O41+ – Dinordehydrobatzelladine B, 90. C38H63N3O6 – Neofolitispate 3, 102. C38H66N6O2 – Norbatzelladine L, 104. C39 C39H32N6O3S – Fradcarbazole A, 792. C39H32N6O9S2 – Plectosphaeroic acid B, 1001. C39H32N6O10S2 – Plectosphaeroic acid A, 1000. C39H54N4O2 – Manadomanzamine A, 915. – Manadomanzamine B, 916. C39H65N3O6 – Neofolitispate 2, 101. C39H68N6O2 – Batzelladine L, 80. C40 C40H36N6O4 – Asperazine, 988. C40H46N4O10 – Tolyporphin A, 531. C40H50Cl2N2O15 – Aurantoside F, 592. C40H67N3O6 – Neofolitispate 1, 100.

C40H67N9O4 – Batzelladine B, 76. C40H69N9O4 – Dinorbatzelladine A, 89. C41 C41H30N2O10S C41H39N2O9S C41H49N7O6S C41H50ClN9O13 C41H51Cl3N2O16 – Rubroside E, 612. C41H67NO17 – Ancorinoside D, 586. C41H69NO17 – Ancorinoside A, 583. – Ancorinoside B, 584. C41H71N9O4 – Norbatzelladine A, 103. C42 C42H35N3O11 – Storniamide A, 428. C42H35N3O12 – Storniamide B, 429. – Storniamide C, 430. C42H35N3O13 – Storniamide D, 431. C42H53Cl3N2O16 – Rubroside F, 613. C42H54Cl2N2O16 – Rubroside A, 608. – Rubroside C, 610. C42H70N4O4S2 – Somocystinamide A, 164. C42H71NO17 – Ancorinoside C, 585. C42H73N9O4 – Batzelladine A, 75. C43 C43H53N5O6 – Meleagrin B, 1027. C43H54Cl2N2O16 – Rubroside B, 609. C44 C44H44Br4N8O12S4 – Cyclobispsammaplin A, 274.

Index 2 Compound Molecular Formula Index

C44H46BrN5O12 – Pentaacetylcelenamide C, 1115 C44H46Br4N8O12S4 – Bisaprasin, 268. – Bispsammaplin A, 269. C44H46Br8N20O9 – Stylissadine A, 432. – Stylissadine B, 433. C44H56Cl2N2O16 – Rubroside D, 611. C45 C45H46BrN5O14 – Hexaacetylcelenamide B, 1107 C45H74N2O13 – Mycapolyol F, 569. C45H78N6O5 – Fromiamycalin, 91. C45H78N6O8 – Monanchocidin B, 96. – Monanchocidin D, 98. C45H80N6O5 – Ptilomycalin A, 105. C45H80N6O6 – Celeromycalin, 82. – Crambescidin 800, 84. – Isocrambescidin 800, 92. C45H80N6O7 – Crambescidin 816, 9. C45H81N3O11 – Shishididemniol A, 332. C45H82ClN3O11 – Shishididemniol B, 333. C46 C46H48BrN5O14 – Hexaacetylcelenamide A, 1106 C46H48N2O6 – Dixiamycin A, 782. – Dixiamycin B, 783. C46H61NO8 – Stachyin B, 1058 C46H80N6O8 – Monanchocidin C, 97. – Monanchocidin E, 99. C46H82N6O7 – Crambescidin 830, 86.

C47 C47H78N2O14 – Mycapolyol E, 568. C47H82N6O6 – Crambescidin 826, 85. C47H82N6O8 – Monanchocidin, 95. C47H84N6O7 – Crambescidin 844, 87. C47H85N6O51+ – Monanchomycalin C, 63. C48 C48H93NO5 – Axidjiferoside B, 127. C49H58N6O – Zamamidine C, 938. C49H60N6O – Zamamidine A, 936. – Zamamidine B, 937. C49H82N2O15 – Mycapolyol D, 567. C49H95NO5 – Axidjiferoside A, 126. C50 C50H97NO5 – Axidjiferoside C, 128. C51 C51H44Br6N6O12 – Sesquibastadin, 310. C51H86N2O16 – Mycapolyol C, 566. C52 C52H54N6O8 – Stephacidin B, 1122 C53 C53H90N2O17 – Mycapolyol B, 565. C54 C54H64MgN4O10 – Geodin A, 601.

443

444

Index 2 Compound Molecular Formula Index

C55 C55H74N4O5 – Phaeophytin A, 527. – Pheophytin a, 529. C55H94N2O18 – Mycapolyol A, 564.

C72 C72H88N8O6 – neo-Kauluamine, 912. C72H94N8O3 – Kauluamine, 911.

Index 3 Compound Organism Source Index This index lists in alphabetical order all 608 marine organism in Latin names in HAMNP Volume 3, following a code sequence of related active compounds. When one hopes to know the English type name of any marine organism, please see an entry of a related compound in the code sequence. For example, if one hopes to know the English common type name of “Haliclona sp.”, from entry 866 of this index, one will know that the Haliclona sp. is a sponge. A Acanthella aurantiaca 467, 482, 506. Acanthella carteri 345, 506. Acanthostrongylophora aff. ingens 917. Acanthostrongylophora ingens 892, 893, 894, 895, 896, 917, 919, 931. Acanthostrongylophora sp. 903, 904, 906, 907, 913, 915, 916, 919, 921, 928, 929, 930. Acanthus ilicifolius 649, 650, 651, 652, 667. Acarnus erithacus 6. Acrostichum aureum 1097, 1108. Actinoalloteichus cyanogriseus WH1-2216-6 1100. Actinomadura sp. 007 789. Actinomadura sp. BCC 24717 710, 819. Adocia sp. 210. Aegiceras corniculatum 603, 604, 605, 606, 1076, 1081, 1083, 1085, 1087, 1088. Aeromonas sp. CB101 724. Agelas cf nemoechinata 507. Agelas cf. mauritiana 449, 454, 471. Agelas clathrodes 344, 460, 461, 464, 468, 474, 478, 479, 480, 481, 483, 506, 506, 507, 509. Agelas conifera 344, 449, 454, 468, 469, 471, 474, 478, 479, 480, 481, 506, 507, 509. Agelas dendromorpha 446. Agelas dispar 462, 463, 478, 479, 480, 481, 485, 506, 509, 1124. Agelas flabelliformis 344. Agelas linnaei 335, 336, 337, 338. Agelas longissima 478, 479, 480, 481, 506, 506, 509. Agelas mauritiana 345, 468, 487, 488, 506, 507. Agelas nakamurai 445, 449, 469, 481, 504, 505, 509, 509, 510, 511, 512. Agelas novaecaledoniae 449, 509. Agelas oroides 238, 239, 344, 345, 506, 519. Agelas sceptrum 506, 509.

Agelas schmidtii 509. Agelas sp. 64, 470, 485, 487, 490, 491, 500, 501, 502, 503. Agelas sp. SS-1003 449, 454, 471, 477, 488, 492, 493, 494, 495, 496, 497, 498, 499, 506, 517, 519. Agelas sventres 516. Agelas wiedenmayeri 506. Alexandrium tamarense 112, 113, 114, 115, 116, 118, 119, 121. Alexandrium tarnavense 108. Alsidium corallinum 550. Alteromonas haloplanktis 198. Alteromonas rubra 526. Alteromonas sp. 582. Amathia alternate 940, 941, 942, 943. Amathia convoluta 222, 223, 224, 225, 324, 325, 545, 546, 547, 548, 549, 676, 677, 678, 679. Amathia tortuosa 8, 970. Amathia wilsoni 540, 540, 541, 542, 543. Amphimedon sp. 898, 899, 901, 905, 908, 910, 914, 917, 920, 923, 925, 927, 934, 938, 939. Amphimedon sp. SS-975 936, 937. Anabaena flos-aquae NRC525.17 1125. Ancorina sp. 59, 583. Annella sp. 668. Antipathes dichotoma 778. Aphanizomenon flos-aquae 119. Aplidium conicum 952. Aplidium cyaneum 55, 56, 57, 58. Aplidium orthium 71. Aplidium sp. 278, 286. Aplysia dactylomela 521, 713. Aplysia kurodai 183, 220, 284, 285, 994. Aplysia limacina 521. Aplysia parvula 521. Aplysina archeri 283. Aplysina cavernicola 276.

446

Index 3 Compound Organism Source Index

Aplysina cavernicola [Syn. Verongia cavernicola] 199. Aplysina fistularis 132, 276. Aplysina insularis 276. Aplysina sp. 240, 1025. Aplysinella rhax 268, 287, 293. Aplysinella sp. 329. Aplysinopsis reticulata 1030. Arenochalina mirabilis 73. Arothron nigropunctatus 106, 107, 109, 110. Aspergillus effuses H1-1 998. Aspergillus elegans 635, 636, 637, 638. Aspergillus flavipes 649, 650, 651, 652, 667. Aspergillus flavus C-F-3 1046, 1057. Aspergillus fumigatus 202, 203, 204, 218, 573, 1099, 1102, 1103. Aspergillus janus IBT 22274 990. Aspergillus nidulans EN-330 1070, 1071. Aspergillus niger 988. Aspergillus ochraceus 173, 175. Aspergillus ochraceus WC76466 1121, 1122. Aspergillus oryzae 1059, 1067. Aspergillus sclerotiorum NRRL 5167 1118. Aspergillus sp. 967, 968, 1112, 1113. Aspergillus sp. MF 297-2 1114. Aspergillus sydowi PFW1-13 571, 573, 1104, 1105. Aspergillus taichungensis 1097, 1108. Aspergillus terreus PT06-2 166, 167. Aspergillus versicolor ZBY-3 208. Aspergillus westerdijkiae 1098. Aspergillus westerdijkiae DFFSCS013 1098, 1118. Aspergillus westerdijkiae SCSIO 05233 172, 173. Astroides calycularis 1008. Astrosclera willeyana 454, 471. Atapozoa sp. 434, 438, 439. Atapozoa spp. 436. Atergatis floridus 108. Auletta cf. constricta 875. Avicennia marina 809. Axinella brevistyla 339, 343, 459, 1128, 1134. Axinella carteri 455, 466, 467, 482. Axinella damicornis 341, 342, 506. Axinella sp. 344, 433, 450, 450, 451, 451, 452, 452, 467, 483, 489, 509, 517, 519, 684, 685, 686, 687, 688, 689.

Axinella verrucosa 458, 467, 481, 482, 506. Axinyssa djiferi 126, 127, 128. B Babylonia japonica 108, 1123. Batzella sp. 9, 73, 75, 76, 77, 78, 84, 105, 1119, 1120. Beneckea gazogenes 526. Bonellia viridis 523. Botrylloides tyreum 271. Botryllus leachi 1135. Botryllus schlosseri 270. Botryllus sp. 270. Bruguiera gymnorrhiza 786, 787. Bugula dentata 427, 440, 441, 442, 443, 444. Bugula longissima 434. Bugula neritina 427. Bunodosoma cangicum 1010. C Callyspongia cf. flammea 1089, 1090, 1091, 1092. Caloglossa leprieurii 729. Calyx nicaeensis 4. Catenicella cribraria 857. Caulerpa cuppresoides 729. Caulerpa okamurai 4. Caulerpa racemosa 4, 728, 729, 730, 766, 767. Caulerpa scalpelliformis 729. Caulerpa serrulata 729. Caulerpa sertularioides 729. Caulerpa taxifolia 729. Celerina heffernani 21, 82, 84, 91, 105. Chaetomium globosum QEN-14 653, 654. Chaetomium sp. 639. Chelonaplysilla sp. 944, 950. Chlorodesmis comosa 4. Chondria armata 550, 556, 557, 558, 559, 560, 570. Chondria atropurpurea 142, 733. Chondria sp. 731, 732. Chromobacterium sp. 394. Chromocleista sp. R721 627, 628. Cladophora densa 3. Cladosporium sphaerospermum 2005-01-E3 594, 595, 596, 597, 598. Clathria calla 83, 104.

Index 3 Compound Organism Source Index

Clathrina clathrus 1129. Clathrina coriacea 796, 798. Clavelina lepadiformis 576, 577. Clavelina picta 631, 632. Cliona celata 951, 981, 1106, 1107, 1115. Cliona chilensis 179. Cliona sp. 428, 429, 430, 431. Cnemidocarpa bicornuta 219. Codium adherens 4. Codium fragile 4. Coniothyrium cereale 1086. Corallistes sp. 525. Corollospora pulchella 574. Costaticella hastata 818, 855, 879. Crambe crambe 9, 84, 86, 87, 92. Crassostrea sp. 524. Cribricellina cribraria 818, 855, 857, 879. Cribrochalina sp. 932. Cristaria plicata 135, 136. Cymbastela cantharella 70, 482. Cymbastela cantharella [Syn. Pseudaxinyssa cantharella] 1134. Cymbastela sp. 446, 447, 448. Cynops ensicauda 106, 108, 109, 110. Cypridina hilgendorfii 60. Cystodytes solitus 799, 802. D Dactylia sp. 350. Dendrilla cactos 264, 351. Dendrilla sp. 944. Dendrodoa grossularia 71. Desmapsamma anchorata 340, 352, 353. Dichotomomyces cejpii 1068, 1074. Dichotomomyces cejpii var. cejpii NBRC 103559 1059. Dictyodendrilla sp. 735. Didemnum conchyliatum 1013, 1014, 1015, 1016. Didemnum sp. 10, 11, 226, 398, 399, 400, 401, 402, 403, 407, 408, 409, 410, 412, 810, 811, 813, 814, 815, 816, 852, 856. Diploprion bifasciatum 25. Discodermia polydiscus 1017, 1022. Distaplia regina 680. Dragmacidon sp. 765. Druinella sp. 240, 307, 308. Drupella fragum 670, 671, 672, 708, 709, 711.

447

Dysidea herbacea 552, 553. Dysidea sp. 212, 817, 1132. E Echinodictyum sp. 739, 740, 741, 1133. Emericella desertorum 1066. Emericella nidulans var. acristata 1066. Emericella sp. 1087, 1088. Emericella striata 1066. Enterobacter sp. 619. Enteromorpha intestinalis 659, 662, 663, 664, 665, 666. Enteromorpha linza 4. Enteromorpha sp. 1086. Enteromorpha tubulosa 1046, 1057. Escherichia coli 669, 759, 760. Eudistoma album 820. Eudistoma fragum 957. Eudistoma gilboverde 829, 830, 831, 836, 837, 838, 871, 872, 873. Eudistoma glaucus 821, 822, 822, 823, 824, 825, 826. Eudistoma olivaceum 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843. Eudistoma sp. 790, 795, 804, 845, 846, 847, 848, 849, 850, 851, 1116, 1117. Eudistoma toealensis 803, 803. Eudistoma vannamei 800, 801, 803. Eunicella granulata 681, 682. Eupenicillium shearii 1078, 1079, 1080. Euplexaura nuttingi 1146, 1147, 1148. Euplexaura robusta 148, 1146, 1147, 1148. Eurotium rubrum 998. Eurythoe complanata 131, 155, 156. Eusynstyela latericius 14, 15, 15, 17, 17. Eusynstyela misakiensis 14. Exophiala sp. 174. Exophiala sp. MFC353-1 171, 173. F Fascaplysinopsis reticulata 810, 856. Fascaplysinopsis sp. 852. Fischerella sp. 1044, 1045, 1055, 1056. Fischerella sp. ATCC43239 1052. Flavobacterium sp. 135, 136. Flavobacterium sp. NR2993 136.

448

Index 3 Compound Organism Source Index

Flustra foliacea 949, 953, 954, 982, 983, 984, 985, 986, 987. Fromia monilis 21, 82, 84, 91. Fugu poecilonotus 111. Fugu spp. 106, 109, 110. Fusarium heterosporum 600. G Gellius sp. 959, 960. Geodia gigas 4. Geodia sp. 601. Gliocladium roseum OUPS-N132 994. Glossobalanus sp. 680. Gonyaulax catenella 120. Gonyaulax spp. 112, 113, 114, 115, 116, 118. Gonyaulax tamarensis 119. Grateloupia livida 3. Gymnascella dankaliensis 140. H Hahella chejuensis 530. Halichondria cylindrata 599. Halichondria japonica 140. Halichondria okadai 582, 701, 702, 743. Halichondria panicea 171, 173, 174. Halichondria sp. 762, 763, 764. Haliclona sp. 866, 905, 908, 910, 917, 920, 1040. Halimeda sp. 146. Halobacillus salinus 150. Halocynthia roretzi 1019, 1020. Halorosellinia oceanica BCC5149 643. Hapalosiphon fontinalis 1047. Hapalosiphon fontinalis ATCC39964 1054. Hapalosiphon laingii 1048, 1049, 1050, 1051, 1053, 1055. Hapalosiphon welwitschii 1048, 1049. Heliopora coerulea 522. Hemimycale sp. 105. Herdmania momus 690, 691, 692, 693, 694, 975, 1021. Hermidium alipes (preferred genus name Mirabilis) 227. Hexadella sp. 777. Homaxinella sp. 134. Homophymia conferta 589. Hormoscilla spp. 393. Hyatella sp. 619, 726. Hymeniacidon aldis 467, 482.

Hymeniacidon sp. 453, 466, 483, 484, 486, 506, 509, 513, 514, 517, 518, 518. Hymeniacidon spp. 467. Hyrtios cf. erecta 852, 856. Hyrtios erecta 862, 1011, 1012. Hyrtios erectus 683, 854. Hyrtios proteus 988. Hyrtios reticulatus 858, 863, 864. Hyrtios sp. 746, 747, 748, 749, 750, 859, 860, 861, 878, 886, 955, 956, 958, 976. I Ianthella basta 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 260, 261, 262, 279, 280, 310, 314, 316, 317. Ianthella cf. reticulata 261. Ianthella flabelliformis 266, 267, 318. Ianthella quadrangulata 248, 249, 250, 251, 256, 257, 263, 265, 327. Ianthella sp. 259, 315, 414. Iotrochota sp. 180, 181. Ircinia sp. 555, 908, 909, 910, 917, 920, 923, 924, 969. Ishige okamurae 137. J Jaspis carteri 184, 190. Jaspis cf. coriacea 184, 185, 188, 189, 190, 191, 193, 194, 195, 196, 197. Jaspis duoaster 1160. Jaspis sp. 65, 66, 184, 185, 197, 268, 269, 272, 274, 277, 287, 288, 289, 290, 293, 311. K Kandelia candel 788. L Lamellaria sp. 397, 404, 405, 406, 408, 410, 411. Lamellodysidea herbacea 551. Laminaria japonica 528, 529. Laurencia brongniartii 713, 715, 716, 719, 725, 727. Laurencia majuscula 729. Laurencia sp. 713. Laxosuberites sp. 349, 395. Leptoclinides dubius 975.

Index 3 Compound Organism Source Index

Leptogorgia gilchristi 1146. Leptosphaeria sp. OUPS-N80 995, 996. Leucetta cf. chagosensis 1137, 1159. Leucetta chagosensis 1138, 1139, 1149. Leucetta leptorhaphis 41. Leucetta microraphis 1140, 1141, 1142. Leucetta sp. 1, 1130, 1136, 1150. Lignopsis spongiosum 874. Lissoclinum fragile 844, 865. Lithoplocamia lithistoides 158, 159. Luffariella geometrica 723. Lyngbya majuscula 138, 139, 157, 160, 164, 164, 228, 561, 562, 563, 578, 965, 1041, 1042, 1043. Lyngbya sp. 161. M Macrocallista nimbosa 4. Marinactinospora thermotolerans SCSIO 00652 867, 868, 869, 870, 1101, 1111. Marinospora sp. NPS12745 754, 755, 756, 757, 758. Melophlus sp. 587, 587, 593. Microascus longirostris 12, 13, 40. Microascus longirostris SF-73 7, 177, 178. Microcoleus sp. 157. Micromonospora sp. L-31-CLCO-02 796, 798. Monanchora arbuscula 79, 88, 89, 90, 103. Monanchora pulchra 63, 67, 67, 68, 69, 95, 96, 97, 98, 99. Monanchora sp. 85, 93, 94. Monanchora unguifera 73, 80, 81. Monodonta labio 26, 27, 28, 29, 30. Monostroma fuscum 227. Moorea producens 145. Mugil cephalus 202, 203, 204. Muricea austera 232. Musa sapientum 227. Mycale cecilia 340, 355, 376. Mycale izuensis 564, 565, 566, 567, 568, 569. Mycale micracanthoxea 354, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374. Mycale microsigmatosa 340, 352, 353. Mycale sp. 349, 356, 357, 358, 359, 360, 361, 362, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 395.

449

Mytilus californianus 120. Mytilus edulis 4, 550, 1112, 1113, 1114. N Nembrotha crista 434, 438, 439. Nembrotha kubaryana 427, 434, 438, 439. Neofolitispa dianchora 100, 101, 102. Neopilema nomurai 640, 655. Nitzschia navis-varingica 556, 557, 558. Nitzschia pungens f. multiseries 550. Nocardiopsis sp. CMB-M0232 999. Notodoris citrina 1131, 1149. Notodoris gardineri 1129, 1131, 1136. O Occurs in animals, esp. in brain nervous system 227. Occurs in blue-green pigment of bile, eggshells and dog placenta, primary product derived from haem in vivo 522. Occurs in diatoms 550. Occurs in higher plants, such as broom Cytisus scoparius, banana 227. Occurs in marine animals eg. Metridium senile 227. Occurs in marine organisms 112, 113, 114, 115, 116, 120. Occurs in plankton blooms 524. Occurs in plants 229, 527. Oceanapia sp. 35. Octopus maculosus 109. Orina sp. 959, 960, 961, 962, 963, 964. Oscillatoria cf. 393. Oscillatoria sp. 160. Ostracion cubicus 737. Ostracion immaculatus 2. P Pachastrissa sp. 184, 185, 188. Pachypellina sp. 903. Paecilomyces variotii EN-291 1109. Patinopecten yessoensis 524. Pellina sp. 917. Penaeus orientalis 176. Penares sollasi 583, 584, 585, 586. Penares sp. 779. Penicillium brevicompactum 989, 990, 991. Penicillium brocae MA-192 809.

450

Index 3 Compound Organism Source Index

Penicillium camemberti OUCMDZ-1492 1061, 1062, 1063, 1064, 1065, 1067, 1069, 1072, 1073, 1075, 1077. Penicillium chrysogenum 1026. Penicillium citrinum N055 575. Penicillium commune isolate GS20 1060. Penicillium commune SD-118 334, 1026. Penicillium griseofulvum 997, 998. Penicillium janthinellum 1078, 1081, 1082, 1084. Penicillium paneum SD-44 213, 214, 215, 714, 880, 881, 887. Penicillium sp. 659, 662, 663, 664, 665, 666, 992, 993, 1003, 1110. Penicillium sp. 386 168. Penicillium sp. BM1689-P 554. Penicillium sp. F23-2 1004, 1005, 1006, 1007, 1026, 1027, 1028, 1029. Penicillium sp. GQ-7 603, 604, 605, 606. Penicillium sp. HKI0459 1076, 1078, 1081, 1083, 1085. Penicillium sp. N115501 124. Penicillium sp. OUPS-79 660, 661. Perknaster fuscus antarcticus 62. Petrosia contignata 932, 933. Petrosia sp. 913, 917. Phakellia flabellata 467. Phakellia fusca 345, 453. Phakellia mauritiana 473. Phidiana militaris 36, 37. Phoma sp. 607, 640, 655. Phorbas topsenti 1151, 1152, 1153. Phyllophora nervosa 229. Pichia membranifaciens USF-HO-25 701, 702. Plakortis nigra 882, 883, 884, 885. Plakortis simplex 978, 979, 980. Plakortis sp. 572. Plectosphaerella cucumerina 1000, 1001, 1002. Poecillastra sp. 268, 269, 274, 277, 287, 288, 289, 290, 293, 311. Poecillastra wondoensis 272. Polyandrocarpa sp. 1031. Polyandrocarpa zorritensis 703, 704, 1162. Polycitorella mariae 734. Polycitorella sp. 752, 753. Polyfibrospongia echina 957. Polyfibrospongia maynardii 956, 976.

Polyphysia crassa 396. Porites cylindrica 157. Prianos sp. 911. Prostheceraeus villatus 576, 576, 577, 577. Prosuberites laughlini 483, 490. Protogonyaulax catenella 122, 123. Protogonyaulax sp. 117, 119. Protogonyaulax spp. 112, 113, 114, 115, 116, 118. Protogonyaulax tamarensis 120. Psammaplysilla purea 235, 300, 301, 1143, 1144, 1145, 1154, 1155, 1156, 1157, 1158. Psammaplysilla purpurea 240, 241, 242, 243, 250, 258, 260, 275, 282, 302, 303, 304, 305, 306, 307, 307, 309, 330, 331. Psammaplysilla sp. 294, 329. Psammoclemma sp. 295, 296, 297, 740, 742. Pseudaxinella sp. 467. Pseudaxinyssa cantharella 506, 1134. Pseudaxinyssa cantharella [Syn. Cymbastela cantharella] 1134. Pseudoalteromonas sp. F-420 146. Pseudoceratina arabica 321, 322, 323, 326, 328, 329. Pseudoceratina crassa 39. Pseudoceratina purpurea 39, 48, 240, 268, 273, 287, 288, 289, 290, 291, 292, 293, 298, 299, 319, 320, 329, 345. Pseudoceratina sp. 38, 205, 221, 1127. Pseudoceratina verrucosa 244, 1154. Pseudoceros sp. 803. Pseudodistoma arborescens 808. Pseudodistoma novaezelandiae 5. Pseudodistoma opacum 876, 877. Pseudokeronopsis riccii 415, 416, 417, 418. Pseudomonas bromoutilis 394. Pseudomonas fluorescens 619, 621. Pseudosuberites hyalinus 673. Ptilocaulis aff. spiculifer 72, 74. Ptilocaulis spiculifer 105. Ptychodera flava 680. Ptychodera flava laysanica 675. Pycnoclavella kottae 971, 972, 973, 974. Pyrodinium sp. 119. R red algae 3. Reniera sp. 1093.

Index 3 Compound Organism Source Index

Rhaphisia lacazei 736. Rhizophora apiculata 1061, 1062, 1063, 1064, 1065, 1067, 1069, 1072, 1073, 1075, 1077. Rhodomela confervoides 129, 130, 133, 149, 620. Rhopalaea sp. 768, 769. Rhopaloeides odorabile 673, 706, 966. Riftia pachyptila 4. Ritterella sigillinoides 829, 837, 841. Rivularia firma 770, 774, 775. Roboastra tigris 434, 435, 436, 437. Rubrobacter radiotolerans 744, 745. Ruditapes philippinarum 524. Ruegeria sp. SANK 71896 211, 216, 217. S Saccharopolyspora sp. 144, 629, 630. Saccoglossus kowalevskii 396. Sarcophyton sp. 635, 636, 637, 638. Sargassum fulvellum 527. Sargassum kjellmanianum 175. Sargassum sp. 967, 968. Sargassum tortile 995, 996. Saxidomus giganteus 119, 120. Schizothrix sp. 164. Serinicoccus profundi sp. nov. 712. Sessibugula sp. 437. Sessibugula spp. 436. Sessibugula translucens 434, 435. Sidnyum turbinatum 170. Siliquariaspongia japonica 590, 591, 592, 608, 609, 610, 611, 612, 613, 614, 615. Siliquariaspongia mirabilis 182. Siliquariaspongia sp. 151, 152, 153, 154. Sinularia brongersmai 51, 53. Sinularia flexibilis 230, 231, 232. Sinularia sp. 42, 49, 50, 51, 52, 53, 54, 162, 163. Sinularia sp. (most likely Sinularia compacya) 50, 51, 52, 53, 54. Smenospongia aurea 957, 958, 1018. Smenospongia cerebriformis 476, 520. Smenospongia echina 958. Smenospongia sp. 674, 852, 945, 946, 947, 948, 1009. Sphoeroides phyreu 108. Sphoeroides rubripes 108. Sphoeroides vermicularis 108.

451

Spicaria elegans 634, 635, 641, 642, 644, 645, 646, 647, 648, 657. Spongosorites genitrix 1023, 1126. Spongosorites ruetzleri 762, 763, 764. Spongosorites sp. 61, 700, 704, 706, 736, 738, 776, 777, 966, 1024. Stachybotrys chartarum 1094. Stachybotrys sp. MF347 1058. Stachybotrys sp. RF-7260 1095. Stachylidium sp. 1089, 1090, 1091, 1092. Stelleta splendens 184. Stelletta sp. 184, 189, 192, 196, 633. Streptomyces fradiae 007M135 792, 793, 794. Streptomyces nitrosporeus 622, 623. Streptomyces seoulensis 176. Streptomyces sp. 579, 580, 581, 616, 625, 786, 805. Streptomyces sp. BA18591 413. Streptomyces sp. BL-49-58-005 699, 977. Streptomyces sp. BOSC-022A 544. Streptomyces sp. CMB-M0406 206. Streptomyces sp. CMB-M0423 346, 347, 348. Streptomyces sp. CNQ-418 423, 424, 425, 426. Streptomyces sp. CNQ-583 624, 626. Streptomyces sp. CNQ-617 421, 422. Streptomyces sp. GT2002/1503 786, 787. Streptomyces sp. HKI0595 788. Streptomyces sp. MM216-87F4 1096. Streptomyces sp. NBRC 105896 1038, 1039, 1040, 1041. Streptomyces sp. QD518 791. Streptomyces sp. SCSIO 02999 780, 782, 783, 785. Streptomyces sp. SCSIO 03032 771, 772, 773, 797. Stylissa caribica 432, 433, 458. Stylissa carteri 458, 513. Stylissa flabellata 432, 433, 472. Stylissa flabelliformis 467. Stylissa massa 466, 482. Stylotella agminata 508. Stylotella aurantium 453, 456, 457, 466, 467, 472, 475, 482, 508, 515. Suberea ianthelliformis 22, 23, 24. Suberea sp. 241, 307, 312, 313. Subergorgia hicksoni 695, 696, 697. Symphyocladia latiuscula 43. Symploca sp. 143, 145.

452

Index 3 Compound Organism Source Index

Synechococcus sp. PCC 7002 165. Synoicum macroglossum 888.

Turbo marmorata 236, 237. Turbo stenogyrus 4.

T Tambja abdere 434, 435, 436, 437. Tambja ceutae 444. Tambja eliora 434, 435, 436, 437. Taricha torosa 108. Tedania ignis 698, 705, 784. Tegella cf. spitzbergensis 16, 18, 19, 20. Telesto riisei 233, 234. Tenacibaculum sp. A4K-17 44, 45, 46, 47. Terrestrial fungi Aspergillus flavipes and Aspergillus microcysticus 635. Terrestrial fungi Drechslera nodulosum and Acremonium lolii 723. Terrestrial fungi Penicillium spp. 1003. Terrestrial fungi Penicillium spp. and Aspergillus spp. 1046. Terrestrial fungus Aspergillus clavatus 641. Terrestrial fungus Aspergillus flavipes 637, 638. Terrestrial fungus Aspergillus fumigatus 573. Terrestrial fungus Aspergillus ochraceus 171. Terrestrial fungus Aspergillus sp. AJ117509 636. Terrestrial fungus Eupenicillium shearii NRRL3324 1073. Terrestrial fungus Rosellinia necatrix 641. Terrestrial plants 4. Theonella sp. 588. Thorecta sp. 1008. Thorectandra sp. 674, 812, 945, 946, 947, 948, 1009. Thorectidae sp. SS-1035 853. Thorectopsamma xana 268, 287. Tolypothrix nodosa 532, 533, 534, 535, 536, 537, 538, 539. Tolypothrix nodosa UH strain HT-58-2 531. Tolypothrix tjipanasensis 806, 807. Topsentia genitrix 776, 777. Topsentia sp. 736. Trachycladus laevispirulifer 1032, 1033, 1034, 1035, 1036, 1037. Trichoderma virens 169. Trikentrion flabelliforme 707, 720, 721, 722. Tubastraea aurea 71. Tubastraea sp. 465, 520.

U Ulosa ruetzleri 1161. Ulva pertusa 653, 654. Unidentified ascidian 144, 419, 420, 544, 621, 781. Unidentified ascidian (family Didemnidae) 332, 333. Unidentified bryozoan 434. Unidentified cyanobacterium 125, 141. Unidentified fish 575. Unidentified fungus dz17 1067. Unidentified green alga 1066. Unidentified mangrove 126, 127, 128, 629, 630, 805, 998, 1067. Unidentified marine bacterium 200, 201. Unidentified marine fungus 137. Unidentified marine-derived actinomycete 147. Unidentified marine-derived actinomycete CNQ-509 388, 389, 390, 391, 392. Unidentified marine-derived actinomycete N96C-47 803. Unidentified marine-derived bacterium 209. Unidentified marine-derived purpre bacterium 210. Unidentified mollusk 579. Unidentified red alga 1070, 1071. Unidentified scyphomedusa (giant jellyfish) 640. Unidentified sponge 7, 12, 13, 40, 177, 178, 467. Unidentified sponge (family Jaspidae) 186, 187, 207. Unidentified sponge (family Petrosiidae) 903, 913. Unidentified sponge (order Haplosclerida, family Petrosiidae) 897, 902, 904, 912, 917, 921, 922, 924. V Verongia aerophoba 281. Verongia cauliformis 132. Verongia cavernicola [Syn. Aplysina cavernicola] 199. Verongia fistularis 132. Verongia spengelii 1008.

Index 3 Compound Organism Source Index

Verongula gigantea 958, 1127. Vibrio nigripulchritudo 34. Vibrio parahaemolyticus 737. Vibrio parahaemolyticus Bio249 761. Vibrio salmonicida 198. Vibrio sp. 119, 726. Vibrio sp. M22-1 619. Vibrio zagogenes ATCC29988 602. Villogorgia rubra 889. W Westiella intricata 1048, 1049.

453

X Xestospongia ashmorica 897, 900, 918. Xestospongia exigua 31, 32, 33. Xestospongia sp. 449, 890, 891, 913, 917, 921, 926, 935. Xestospongia testudinaria 1094. Xylaria sp. 656, 658. Xylaria sp. PSU-F100 668. Z Zoobotryon verticillatum 717, 718. Zopfiella latipes CBS 611.97 617, 618. Zyzza massalis 1031.

Index 4 Compound Sampling Geographic Locality Index In this index, all geographic locations in HAMNP Volume 3 have been devided as 17 large areas: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

CHINA JAPAN RUSSIA KOREA WATERS R. O. KOREA ASIA AUSTRALIA OCEANIA EUROPE AFRICA USA NORTH AMERICA CARIBBEAN SEA SOUTH AMERICA PACIFIC OCEAN ATLANTIC OCEAN ANTARCTIC/ARCTIC

For all 186 compound sampling geographic locations, each of them has put into one large area, and then within the area, all related geographic places are listed in alphabetical order with the detail information in the texts of the “Encyclopedia of Active Marine Natural Products Volume 3” and a number code sequence of the related compounds follows the detail information immediately. There are 810 related compounds with geographic information in EAMNP Volume 3. 1 CHINA China, China waters 175, 218, 571, 573, 603, 604, 605, 606, 634, 642, 644, 647, 648, 649, 650, 651, 657, 728, 1076, 1081, 1083, 1104. China, Dalian, Liaoning 129, 130, 133, 149, 620. China, Fujian 998. China, Haikou, Hainan 1087, 1088. China, Hainan 36, 37, 683, 805, 854. China, Jiaozhou Bay, Shandong 792, 793, 794. China, Lingshui, Hainan 817, 1132. China, Putian, Pinghai 1046, 1057. China, Qingdao coast, Shandong 653, 654. China, Qingdao, Shandong 43, 176. China, South China Sea 870. China, Weizhou coral reef, Guangxi 635, 636, 637, 638.

China, Weizhou I., Guangxi 148, 1146, 1147, 1148. China, Wenchang, Hainan 1061, 1062, 1063, 1064, 1065, 1067, 1069, 1072, 1073, 1075, 1077. China, Xiamen Sea 724. China, Xisha Is., South China Sea 1094. China, Zhanjiang coastline 730. South China Sea, South China Sea 168, 656, 658, 778, 779, 780, 782, 783, 785, 786, 867, 868, 869, 1098, 1098, 1110. Taiwan, Taiwan waters 725, 727. 2 JAPAN Japan, Amami-Oshima 93, 94. Japan, Cape Sada, Ehime prefecture 1160. Japan, Japan waters 25, 26, 27, 28, 29, 30, 42, 65, 66, 108, 111, 124, 134, 236, 237,

Index 4 Compound Sampling Geographic Locality Index

241, 273, 302, 303, 304, 305, 306, 307, 330, 331, 339, 343, 459, 559, 560, 583, 590, 591, 592, 599, 670, 671, 672, 701, 702, 708, 709, 711, 890, 891, 914, 926, 934. Japan, Katsuura Bay 203, 204. Japan, off Osaka 140. Japan, off Ukejima I., near Amami Oshima I. 584, 585, 586. Japan, sea bottom of Uchiura Bay 554. Japan, Southern Japan 48, 319, 320. Japan, Suruga 1123. Japan, Tateyama City, Chiba 144, 1040. Okinawa, Ie I. 510, 511, 512, 825, 826. Okinawa, Iriomote I. 136. Okinawa, Ishigaki I. 629, 630, 967, 968. Okinawa, Kerama I. 64, 501, 502, 503, 746, 747, 748, 899, 905. Okinawa, Kinwan Bay 242, 282. Okinawa, Kume I. 1. Okinawa, off Seragaki 449, 454, 471, 477, 488, 492, 493, 494, 495, 496, 497, 498, 499, 506, 517, 519. Okinawa, Okinawa 235, 241, 301, 307, 312, 313, 453, 466, 467, 481, 482, 485, 486, 491, 500, 513, 517, 518, 572, 749, 750, 752, 753, 768, 769, 821, 822, 823, 824, 853, 898, 908, 909, 910, 917, 917, 920, 923, 924, 925, 927, 969, 1011, 1012, 1025, 1143, 1144, 1145, 1155, 1156, 1157, 1158. Okinawa, Seragaki 901, 936, 937, 938. Okinawa, Zamami 939. 3 RUSSIA Kuril Is., Kuril Is. 63, 67, 68, 69. Russia Russia 1081, 1082, 1084. Russia Urup I. 67. Sea of Okhotsk, Russia near Urup I., Southern Okhotsk Sea 95, 96, 97, 98, 99. 4 KOREA WATERS Korea waters 137, 171, 173, 174, 633, 845, 846, 847, 848, 849, 850, 851, 1023, 1126. 5 R. O. KOREA Jeju I. Jeju I. 691, 692, 693, 694, 975, 1021. Jeju I. off coast of Jeju I. 706, 966. Southern coast Southern coast of R.O.Korea 640, 655.

455

6 ASIA Bay of Bengal 771, 772, 773. India waters 888, 1121, 1122. India Mandapam, Tamil Nadu 275, 307, 309. Indian Ocean Andaman Is. 100, 101, 102. Indonesia 466, 892, 903, 906, 907, 911, 913, 915, 916, 917, 919, 921, 929, 930, 931. Indonesia Ambon 310, 449, 469, 504, 505, 509. Indonesia Java 455. Indonesia Lembeh Strait, North Sulawesi 975. Indonesia N. Sulawesi 863, 864. Indonesia North Sulawesi 162, 163. Indonesia Sulawesi 903, 913. Indonisia 903. Indonisia Sulawesi 260. Indo-Pacific Sea Indo-Pacific 765, 897, 902, 904, 912, 917, 921, 922, 924. Indo-Pacific Sea Indo-Pacific Sea 1131. Israel 1044, 1045. Malaysia N. Borneo I., Sabah 713. Philippines 589, 897, 900, 918. Philippines Siquijor I. 270. Red Sea 105, 467, 482, 551, 859, 860, 861, 862, 1149. Sea of Japan Northern Sea of Japan 1116, 1117. Thailand 643. Thailand Similan Is., Phangnga 668. Yemen Hanish I., Yemen 465. 7 AUSTRALIA Australia 22, 23, 24, 61, 184, 185, 197, 278, 286, 344, 407, 450, 451, 452, 684, 685, 686, 687, 688, 689, 857, 878, 886. Australia Bass Strait, Tasmania (State) 8, 414. Australia Great Australian Bight 433, 450, 451, 452, 467, 483, 489, 517, 519, 739, 740, 741. Australia Hook Reef Lagoon, Queensland 244. Australia Jamieson Reef, Bonaparte Archipelago 184, 189, 192, 196. Australia New South Wales 259, 351. Australia northern New South Wales 970. Australia Northern Rottnest Shelf, Western Australia 398, 399, 400, 401, 402, 403. Australia South Molle I., Brisbane 999. Australia Wasp I., New South Wales 398, 399, 400, 401, 402, 403. Great Barrier Reef, Australia Erskine I. 38.

456

Index 4 Compound Sampling Geographic Locality Index

Great Barrier Reef, 14, 15, 17, 238, 239, 270, 315, 467, 1129, 1130, 1150. Northwestern Australia King George River, Northwestern Australia 125, 141. Queensland 327. Queensland Coral Sea 446, 525. Queensland Curacao I. 180, 181. Queensland Heron I. 206, 346, 347, 348. Queensland Townsville 553. Southern Australia 601, 1024. Southern Australia beach of Southern Australia 147. Tasmania 440, 441, 442, 443. Tasmania Point Peur, Tasman Penninsula 540, 541. Tasmania Waterfall Bay 59. Western Australia 446, 447. Yap Sea, Australia Yap Sea 457, 515. 8 OCEANIA Federated States of Micronesia Chuuk Atoll 233, 234. Federated States of Micronesia Nama I., Chuuk Lagoon 182. Federated States of Micronesia Pohnpei I. 258, 795. Federated States of Micronesia Yap 639. Fiji 184, 184, 185, 188, 189, 190, 191, 193, 194, 195, 196, 197, 207, 240, 307, 308, 487, 1129. Fiji Cicia, Lau group of Fiji 587, 593. Fiji Korolevu 467. Fiji Motualevu Reef 151, 152, 153, 154. Fiji near Kia I. 955. Fiji Pratt Reef 811, 856. Nauru Nauru, Oceania 50, 51, 52, 53, 54. New Zealand 7, 177, 178, 219, 542, 543, 550, 781, 818, 829, 837, 841, 855, 857, 879, 971, 972, 973, 974. New Zealand Auckland 876, 877. New Zealand Tiwai Pt., Southland 10, 11. Palau, Oceania 146, 456, 467, 467, 552, 680, 829, 830, 831, 836, 837, 838, 872, 882, 883, 884, 885, 1140, 1141. Palau, Oceania near Koror 397, 404, 405, 406. Palau, Oceania Peleliu I. 574. Palau, Oceania Western Caroline I. 508.

Papua New Guinea 31, 32, 33, 143, 160, 228, 875, 932, 932, 933, 965, 1050, 1051, 1053. Papua New Guinea Bismarck Sea 858. Papua New Guinea Kime Bay, New Britain I. 145. Papua New Guinea Milne Bay 261. Papua New Guinea New Ireland 160. Papua New Guinea off Papua New Guinea coast 935. Vanuatu 212. 9 EUROPE Baltic Sea, Germany Fehmarn I., Germany 1086. Europe 550. France Marseille 1151, 1152, 1153. Guadeloupe I. (Fr.) 83, 104. Mediterranean Sea 92, 170, 199, 276, 341, 342, 1066. Mediterranean Sea Bay of Taranto 703, 704, 1162. North Sea 761, 982, 983. North Sea Danish 984. North Sea, Germany Steingrund, North Sea coast 949, 953. Norway waters off Bergen 576, 577. Portugal Azores, Atlantic Ocean 444. Scotland Scottish Coast 544. Spain 354, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 1135. Spain Canary Is. 796, 798. 10 AFRICA Egypt Hurghada 321, 322, 323, 326, 328, 329. Madagascar 158, 159. Mozambique near Ponto Malongane 1146. Senegal Djifer 126, 127, 128. Seychelles Seychelles 473. Tanzania Pemba I. 1146, 1147, 1148. West Africa 790, 804. 11 USA Alaska, USA 120. California, USA 108. California, USA La Jolla 423, 424, 425, 426. California, USA San Clemente 625.

Index 4 Compound Sampling Geographic Locality Index

California, USA Uni. of California, Santa Cruz 674, 945, 946, 947, 948, 1009. Florida, USA 222, 223, 224, 225, 324, 325, 545, 546, 547, 548, 549, 988. Florida, USA Gulf of Mexico coast of Florida 676, 677, 678, 679. Grenada, USA True Bay 138, 139. Guam, USA 157, 161, 226, 316, 317, 578. Hawaii, USA 243, 1041. North Carolina, USA 940, 941, 942, 943. Puerto Rico Aguadilla 483, 490. San Francisco, USA San Francisco Bay 616. Sea of Cortez 435. 12 NORTH AMERICA Canada British Columbia 1000, 1001, 1002. Canada Minas Basin, Bay of Fundy 985, 986, 987. Canada Minas Basin, Nova Scotia 982, 983. Gulf of Mexico 627. Panama 476. Panama Coiba National Park 160. 13 CARIBBEAN SEA Bahamas Caribbean Sea 78, 516, 1013, 1014, 1015, 1016, 1124, 1127. Bahamas north point of Acklins I. 1022. Bahamas off Chub Cay, Barry Is. 1017. Caribbean Sea 75, 76, 77, 79, 105, 340, 352, 353, 460, 462, 463, 478, 478, 478, 478, 479, 479, 479, 479, 480, 480, 480, 480, 481, 481, 481, 481, 485, 506, 506, 506, 506, 776, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 865, 956, 978, 979, 980, 1119, 1120.

457

Curacao I., Caribbean Sea 143, 1127. Grand Bahama I. off Grand Bahama I., Caribbean 1022. Jamaica 1018. Martinique I. (Fr.), Caribbean Sea 88, 89, 90, 103. 14 SOUTH AMERICA Argentina 731, 732. Argentina Patagonia 179. Argentina Punta Verda, near San Antonio Oeste, Rio negro 428, 429, 430, 431. Brazil west coast of Ceara state 800, 801, 803. Venezuela 276, 340, 352, 353. 15 PACIFIC OCEAN Central Pacific Ocean Palmyra Atoll 419, 420. Mariana Is., Pacific Ocean Rota, Northern Mariana Is. 813, 814, 815, 816, 1159. New Caledoinia (Fr.) 21, 70, 82, 84, 91, 105, 190, 820, 889, 957, 959, 960, 961, 962, 963, 964. Pacific Ocean along Pacific coast of North and Central America 550. Palmyra Atoll North beach 393. 16 ATLANTIC OCEAN Atlantic Ocean South Georgia I. 874. Bermuda 1161. North Atlantic Ocean Bear I. 16, 18, 19, 20. 17 ANTARCTIC/ARCTIC Antarctic 41, 62, 434. Antarctica 55, 56, 57, 58. Arctic Ocean, Arctic Chukchi Sea 622, 623.

Index 5 Compound Pharmacological Activity Index In this index, a set of very formatted pharmacological activity codes have been used, specially for all types of cancer cells, please see “List of Cancer Cells Codes”. A special note is that the word “Cytotoxic” means in vitro anticancer activities, while the word " Antineoplastic" means in vivo anticancer activities. A A lead as an oncological therapeutic 466. A new lead for development of inhibitor of influenza viruses 998. A new lead to inflammation therapy 1141. A promising drug for cancer treatment 159. ABCG2 inhibitor 271. Acaricide 1041. AChE inhibitor 744, 745, 1110. Activater of ATPase, rabbit heart muscle actomyosin 822. Active in p56lck-CD4 dissociation assay 79. Actomyosin ATPase activator 449, 454, 471, 507. Acts as photosensitizer 531. Acute toxicity 508. Adenylate cyclase inhibitor 1055, 1056. Adjunct in treatment of hypercholesterolaemia 4. Adrenergic 227. Adrenergic antagonist 506, 509. Affinity for 5-HT2A and 5-HT2C receptors 1018. Affinity for neuronal nicotinic acetylcholine receptors, radioligand binding assay 949. Affinity to nACh receptors, high and subtype selective 953, 954. Agonist of CB1 cannabinoid receptor, selective 160. AIDS opportunistic infectious pathogens 80, 81. Algicide 673, 1047. Alkaline phosphatase inhibitor 394. Aminopeptidases inhibitor 394. Amnesic shellfish poison 550. AMPA-binding assay, quisqualate site of glutamate receptor 959. Analgesic, could be used in the medical field as an Analgesic to treat some cancer pains 108. Analgetic 669.

Analgetic effects mediated via serotonin receptors 1010. Ancorinosides are 10 times less potent than FN-439 for MT1-MMP inhibitor activity 584, 585, 586. Antagonist of epidermal growth factor receptor 1149. Antagonist of RyR1-FKBP12 Ca2+ channel, ryanodine binding, opposite effect of Bastadin 5 316, 317. Antagonist of veratridine-induced Sodium infiux, murine cerebrocortical neurons 143. Antagonistic, cannabinoid receptor CB2 1092, 1091. Antagonistic, histamine receptor H2, dopamine receptor DAT and adrenergic receptor 1090. Anthelminthic 184, 185, 188, 194, 195, 556, 557, 1131. Anthelminthic, in vitro 189. Anthelminthic, in vivo 189. Anthelmintic 142, 186, 187, 197, 207, 731, 733. Anti-AD, clinical trial, July 2007 Bellus Health Inc 3. Anti-AD, inhibits amyloid A fibril formation and deposition, using in treatment of Alzheimer’s disease and cerebral amyloid Angiopathy 3. Anti-AD, preclinical trial, Russo, 2016 1142. Antiallergic 775. Anti-Alzheimer’s agents 414. Antiangiogenic 250. Antiangiogenic, matrixmetalloproteinase inhibitor 445. Antibacterial 199, 238, 239, 280, 396, 468, 488, 489, 507, 673, 680, 715, 716, 719, 737, 739, 740, 741, 809, 817, 900, 918, 944, 950, 1020, 1031, 1047, 1054, 1132. Antibacterial inactive, Bacillus cereus 1019.

Index 5 Compound Pharmacological Activity Index

Antibacterial inactive, Bacillus megaterium 1019. Antibacterial inactive, Bacillus subtilis 428, 429, 430, 431, 477, 1019. Antibacterial inactive, Bacillus subtilis SCSIO BS01 780, 785, 786. Antibacterial inactive, Bacillus thuringiensis SCSIO BT01 780, 785, 786. Antibacterial inactive, Enterobacter aerogenes 166. Antibacterial inactive, Escherichia coli 72, 74, 275, 307, 477, 818, 829, 831, 835, 842, 843, 855, 857, 859, 860, 861, 879. Antibacterial inactive, Escherichia coli ATCC 25922 780, 785, 786. Antibacterial inactive, Helicobacter pylori associated with pepticular and gastric cancer 450, 452. Antibacterial inactive, Micrococcus luteus 428, 429, 430, 431, 477, 575. Antibacterial inactive, MREC 619. Antibacterial inactive, MRSA 152, 153, 154, 390, 391, 392. Antibacterial inactive, Proteus vulgaris 464. Antibacterial inactive, Pseudomonas aeruginosa 166, 167, 818, 855, 857, 879. Antibacterial inactive, Salmonella typhi 275. Antibacterial inactive, Shigella flexneri 309, 464. Antibacterial inactive, Staphylococcus aureus 72, 74, 153, 154, 167, 275, 307, 428, 429, 430, 431, 464. Antibacterial inactive, Staphylococcus aureus ATCC 29213 780, 785, 786. Antibacterial inactive, Staphylococcus epidermidis 335, 336, 337, 338. Antibacterial inactive, Streptococcus faecalis 72, 74. Antibacterial inactive, Streptococcus pneumoniae 72. Antibacterial inactive, Vibrio cholera 275, 307. Antibacterial, Acinetobacter calcoaceticus 617. Antibacterial, Agrobacterium tumfaims 844, 865. Antibacterial, Arthrobacter citreus 617. Antibacterial, Bacillus brevis 617. Antibacterial, Bacillus cereus 213PCl 509.

459

Antibacterial, Bacillus licheniformis 617. Antibacterial, Bacillus megaterium 856, 1019. Antibacterial, Bacillus subtilis 147, 300, 449, 454, 471, 492, 493, 494, 495, 496, 497, 498, 499, 500, 502, 503, 506, 571, 573, 617, 708, 709, 711, 735, 738, 818, 829, 829, 830, 831, 835, 837, 838, 840, 841, 842, 843, 845, 846, 847, 848, 849, 850, 851, 855, 857, 879, 914, 925, 940, 941, 942, 1019, 1045, 1058, 1124. Antibacterial, Bacillus subtilis 168 449, 469, 504, 505, 509. Antibacterial, Bacillus subtilis 6633ATCC 509. Antibacterial, Bacillus subtilis ATCC 6051 506, 489, 433, 451, 483, 519, 517. Antibacterial, Bacillus subtilis ATCC 6633 433, 451, 483, 485, 489, 506, 517, 519. Antibacterial, Bacillus subtilis SCSIO BS01 782, 783. Antibacterial, Bacillus thuringiensis SCSIO BT01 782, 783. Antibacterial, Corynebacterium glutamicum 18, 19, 20, 15. Antibacterial, Corynebacterium insidiosum 617. Antibacterial, Corynebacterium xerosis 769, 914. Antibacterial, Cryptococcus neoformans 747, 748. Antibacterial, Edwardsiella tarda 1070. Antibacterial, Enterobacter aerogenes 167. Antibacterial, Enterococcus faecelis 940, 941, 942. Antibacterial, Enterococcus faecium 940, 941, 942, 1044. Antibacterial, Escherichia coli 15, 18, 19, 20, 309, 334, 334, 449, 454, 471, 492, 493, 494, 495, 496, 497, 498, 499, 502, 503, 506, 509, 571, 573, 708, 709, 711, 738, 829, 830, 837, 838, 840, 841, 852, 856, 1070. Antibacterial, Escherichia coli and Staphylococcus aureus 953. Antibacterial, Escherichia coli ATCC 11775 506, 489, 433, 483, 519, 986, 987, 517. Antibacterial, Escherichia coli ATCC 25922 449, 509, 782, 783, 874. Antibacterial, Escherichia coli ESS K-12 1045. Antibacterial, Escherichia coli HB101 449, 509.

460

Index 5 Compound Pharmacological Activity Index

Antibacterial, Escherichia coli permeability mutant 619, 621. Antibacterial, fish in aquaculture, against diseases caused by gram-negative bacteria 146. Antibacterial, fish pathogen Vibrio anguillarum 332, 333. Antibacterial, gram-positive and -negative bacteria 506, 917. Antibacterial, gram-positive bacteria 179, 245, 246, 247, 248, 346, 347, 348, 394, 427, 723, 828, 1093, 1124. Antibacterial, gram-positive bacteria, particularly the spore bearers 602. Antibacterial, gram-positive bacterium Bacillus subtilis 542, 543. Antibacterial, gram-positive bacterium Corynebacterium xerosis 927. Antibacterial, in vitro not in vivo, gram-positive and gram-negative bacteria 956. Antibacterial, in vitro not in vivo, gram-positive and -negative bacteria 976. Antibacterial, marine bacterium Pseudomonas spp. 1093. Antibacterial, Micrococcus luteus 312, 313, 449, 454, 471, 492, 493, 494, 495, 496, 497, 498, 499, 500, 502, 503, 506, 617, 735, 853. Antibacterial, Micrococcus luteus ATCC 49732 986, 987. Antibacterial, Micrococcus lysoleikticus 571, 573. Antibacterial, MREC 621. Antibacterial, MRSA 15, 18, 19, 20, 80, 81, 151, 151, 388, 389, 423, 424, 425, 426, 619, 619, 621, 621, 668, 754, 754, 755, 755, 756, 756, 757, 757, 758, 788, 1058, 1059. Antibacterial, Mycobacterium phlei 617. Antibacterial, Mycobacterium sp. 925. Antibacterial, Pseudomonas aeruginosa 15, 18, 19, 20, 509, 859, 860, 861. Antibacterial, Pseudomonas aeruginosa ATCC 10145 489, 506, 433, 483, 517, 519. Antibacterial, Pseudomonas aeruginosa, selective 22, 23, 24. Antibacterial, quorum sensing, MMOA: inhibits homoserine lactone receptor binding 150.

Antibacterial, Salmonella typhi 1943OATCC 509. Antibacterial, Sarcina lutea 300, 769, 914, 925. Antibacterial, Staphylococcus albus 1045. Antibacterial, Staphylococcus aureus 15, 16, 18, 19, 20, 80, 81, 151, 151, 152, 166, 241, 242, 300, 302, 303, 304, 305, 306, 307, 307, 309, 330, 331, 334, 334, 500, 502, 503, 668, 708, 709, 711, 747, 748, 852, 859, 860, 861, 925, 939, 1026, 1044, 1070, 1124. Antibacterial, Staphylococcus aureus 6538ATCC 509. Antibacterial, Staphylococcus aureus ATCC 25923 433, 449, 483, 489, 506, 509, 517, 519, 712. Antibacterial, Staphylococcus aureus ATCC 29213 782, 783. Antibacterial, Staphylococcus aureus ATCC 9144 433, 483, 489, 506, 517, 519. Antibacterial, Staphylococcus aureus ATCC6538 485. Antibacterial, Staphylococcus aureus oxacillin resistant 619, 621. Antibacterial, Staphylococcus aureus oxacillin, gentamicin and ciprofloxacin resistant 619, 621. Antibacterial, Staphylococcus epidermidis 674, 940, 941, 942, 945, 946, 947, 948, 1009, 1058. Antibacterial, Staphylococcus epidermis 845, 846, 847, 848, 849, 850, 851. Antibacterial, Staphylococcus Haemolyticus 940, 941, 942. Antibacterial, Staphylococcus sp. 713. Antibacterial, Streptococcus faecalis 509. Antibacterial, Streptococcus pneumoniae 74. Antibacterial, Streptococcus pyogenes 72, 74, 940, 941, 942. Antibacterial, Streptomyces sp. 617. Antibacterial, Streptomyces viridochromogenes 791. Antibacterial, Vibrio anguillarum 1070. Antibacterial, Vibrio cholera 309. Antibacterial, VREF 619, 621, 754, 755, 756, 757, 758, 788. Antibiotic 132, 351, 634, 642, 943, 1008. Antibiotic, Penicillium notatum 508.

Index 5 Compound Pharmacological Activity Index

Anticancer-Cell-Effect 228, 965. Antifeedant 344, 396, 438, 439, 552, 1118. Antifeedant, broad actions 578. Antifeedant, deterrent for ascidians 345. Antifeedant, fish 684, 686, 688, 1014, 1015, 1016. Antifeedant, predator deterrent 1013, 1014. Antifeedant, reef fish Thalassoma bifasciatum 516. Antifoulant 172, 449, 474, 475, 488, 506, 507, 673, 695, 696, 697. Antifoulant, barnacle Balanus amphitrite 39. Antifoulant, barnacle Balanus amphitrite cypris larvae 273. Antifoulant, bryozoan Bugula neritina larval settlement 1098. Antifoulant, inhibits moulting of cyprid larvae of barnacles 457, 515. Antifoulant, larval settlement of barnacle Balanus amphitrite 635, 636, 637, 638. Antifungal 43, 226, 287, 508, 633, 639, 730, 803, 806, 807, 915, 916, 1024, 1031, 1059, 1142. Antifungal inactive, Alternaria brassicae 334. Antifungal inactive, Aspergillus fumigatus 587, 588, 590, 591. Antifungal inactive, Aspergillus niger 491, 1137. Antifungal inactive, Candida albicans 166, 167, 421, 422, 587, 588, 627, 710. Antifungal inactive, Cladzspwum resina 818, 855. Antifungal inactive, Cryptococcus neoformans 575, 1019. Antifungal inactive, Penicillium atrovenetum 829, 831, 834, 842. Antifungal inactive, Saccharomyces cerevisiae 829, 829, 831. Antifungal, ARCA 593. Antifungal, Aspergillus niger 460, 461, 462, 463, 502, 503, 593. Antifungal, Aspergillus oryzae 732. Antifungal, Botrytis cinerea 984. Antifungal, Candida albicans 16, 19, 64, 105, 298, 299, 300, 501, 502, 503, 590, 591, 593, 723, 747, 748, 762, 763, 764, 852, 859, 860, 861. Antifungal, Candida albicans 738.

461

Antifungal, Candida albicans ATCC 90028 433, 483, 506, 519. Antifungal, Candida albirnns 818, 855, 857, 879. Antifungal, Candida utilis ATCC 9950 986, 987, 985. Antifungal, Cladosporium sphaerospermum 218. Antifungal, Cladzspwum resina 857, 879. Antifungal, Cryptococcus neoformans 593, 502, 503, 735, 300, 73. Antifungal, Cryptococcus neoformans 738. Antifungal, Cryptococcus neoformans 32609 728. Antifungal, erg6 mutant of Saccharomyces cerevisiae 339, 343, 459. Antifungal, microzyme 852. Antifungal, mutant Saccharomyces cerevisiae 298, 299. Antifungal, Nematospora coryli 617, 618. Antifungal, Paecilomyces variotii 300. Antifungal, Penicillium atrovenetum 829, 830, 837, 838, 840, 841. Antifungal, Penicillium sp. 593. Antifungal, Rhizoctonia solani 984. Antifungal, Rhizopus sporangia 593. Antifungal, Saccharomyces cerevisiae 617, 618, 830, 834, 837, 838, 840, 841, 842, 1128. Antifungal, Saccharomyces cerevisiae ATCC 9763 986, 987. Antifungal, Sordaria sp. 593. Antifungal, Trichophyton mentagrophytes 502, 503, 542, 543, 732, 747, 748, 818, 855, 857, 879, 927. Antifungal, wide spectrum 593. Antifungal, yeast 828, 1020. Antihistamine 509. Antihistaminic 978, 979, 980. Antihistaminic, gpg ileum 506, 519. Antihistaminic, gpg ileum, remarkable, spesific reversible non-compapetitive effect 478, 479. Antihistaminic, gpg ileum, reversible noncompapetitive effect 480, 481. Anti-HIV 125, 141, 600, 607. Anti-HIV, inhibition of fusion between the viral envelope and the endosome 1095. Anti-HIV-1 915, 916. Anti-HIV-1, cells CEM 4 infacted by HIV-1 21, 82, 84, 91, 105.

462

Index 5 Compound Pharmacological Activity Index

Anti-HIV-1, inhibits replication of HIV-1 by targeting reverse transcriptase and blocks non-nucleoside reverse transcriptase inhibitor-resistant strains 1094. Antihyperplastic 803. Antihypertensive 483. Antihypotensive 227. Antihypotensive, in large doses 229. Anti-inflammatory 230, 231, 232, 248, 252, 253, 254, 255, 280, 467, 482, 580, 581, 770, 774, 775. Anti-inflammatory, modulation of LPS-activated brain microglia, MMOA: - TXB2 inhibition 902, 904, 917. Anti-inflammatory, neutrophil chemotaxis inhibitor 458. Anti-inflammatory, using activated hmn peripheral blood neutrophils 974. Antiinsectan activity 1078. Anti-invasive 1060. Anti-invasive activity highly metastatic MDAMB-231 321, 322, 323, 326, 328, 329. Antileishmanial 340. Antileishmanial inactive, Leishmania major 1089. Antileishmanial, Leishmania donovani 73, 917, 876, 877, 897, 921, 903, 10, 11. Antimalarial 915, 916. Antimalarial, in vivo 922. Antimalarial, in vivo, strong 904. Antimalarial, Plasmodium berghei in vivo, potent and no apparent toxicity 903, 912. Antimalarial, Plasmodium berghei in vivo, no apparent toxicity 913. Antimalarial, Plasmodium falciparum 643. Antimalarial, Plasmodium falciparum K1 876, 877. Antimalarial, Plasmodium falciparum K1, MMOA: - FabI inhibition 506. Anti-metabolic 974. Antimicroalgal, Chlorella sorokiniana 791. Antimicroalgal, Chlorella vulgaris 791. Antimicroalgal, Scenedesmus subspicatus 791. Antimicrobial 6, 39, 61, 124, 184, 185, 210, 268, 287, 289, 434, 435, 436, 437, 631, 632, 707, 720, 721, 722, 726, 746, 749, 750, 754, 951, 957, 958, 981, 1106, 1107, 1115, 1116, 1117, 1129.

Antimicrobial, broad spectrum 755, 756, 757, 758. Antimicrobial, in vivo 49. Antimicrobial, potent 734. Antimigratory activity, wound healing assay, highly metastatic MDA-MB-231 321, 322, 323, 326, 328, 329. Antimitotic 205. Antimitotic, HeLa, mitotic ratio of cell culture was determined using a specific microplate immunoassay ELISA 55, 56, 57, 58. Antimitotic, modified cell-based immunoassay, using specific mitotic marker MPM-2 158, 159. Antimuscarinic 483, 506, 509. Antimycotic 1047, 1054. Antineoplastic 736, 777. Antineoplastic, in vivo 413, 446, 1008, 1024, 1134. Antineoplastic, in vivo, leukemia 1041. Antineoplastic, in vivo, phase I clinical trials in 2011 159. Antioxidant 524, 1151, 1152, 1153. Antioxidant, ABTS∙+ radical cation scavenger 129, 130, 133, 149, 620. Antioxidant, DPPH radical scavenger 129, 130, 133, 137, 149, 175, 620, 701, 702, 859, 860, 861. Antioxidant, free radical scavenger, to protect N18-RE-105 cells against L-glutamate toxicity 967, 968. Antioxidant, high activity 997. Antioxidant, oxygen radical absorbance 955, 958. Antioxidant, POV Peroxide value method 670, 671, 672. Antioxidant, radical scavenger 628. Antioxydant, hmn neutrophils 579, 580, 581. Antiparasitic 184, 185, 803, 1131. Antiparkinsonian 227. Antiplasmodial, chloroquine-susceptible Plasmodium falciparum NF54 852. Antiplasmodial, CRPF 126, 127, 128, 540, 541, 970. Antiplasmodial, CRPF FcB1 465. Antiplasmodial, CSPF 540, 541, 970. Antiplasmodial, CSPF F32 465.

Index 5 Compound Pharmacological Activity Index

Antiplasmodial, CSPF NF54 856. Antiplasmodial, Dd2 Multi-drug-resistant line 867, 868, 869, 870, 1101, 1111. Antiplasmodial, life stage-specific activity Plasmodium falciparum strain W2-Mef, All live parasites 811, 856. Antiplasmodial, life stage-specific activity, Plasmodium falciparum strain W2-Mef 852. Antiplasmodial, liver stage of Plasmodium berghei 1089, 1090, 1091. Antiplasmodial, Plasmodium falciparum 93, 94, 901, 917, 936, 938. Antiplasmodial, Plasmodium falciparum 3D7 59. Antiplasmodial, Plasmodium falciparum 3D7 Drug-sensitive line 867, 868, 869, 870, 1101, 1111. Antiplasmodial, Plasmodium falciparum D6 905. Antiplasmodial, Plasmodium falciparum Dd2 59. Antiplasmodial, Plasmodium falciparum FcB1 75, 80, 83, 88, 89, 90, 103, 104, 105. Antiplasmodial, Plasmodium falciparum K1 10, 11, 616, 852, 856. Antiplasmodial, Plasmodium falciparum W2 905. Antiproliferation 173. Antiproliferative 190, 196, 197. Antiproliferative MDA-MB-435 189, 185. Antiproliferative, MDA-MB-435 188, 194, 191, 193, 184. Antiserotonergic, prophage induction 509. Antiserotonin 961, 962, 963, 964. Antitoxoplasma, Toxoplasma gondii 904. Antitoxoplasma, Toxoplasma gondii, without host cell toxicity 917, 922. Antitrypanosomal, Trypanosoma brucei brucei 8, 93, 94, 901, 936, 938, 1089. Antitrypanosomal, Trypanosoma brucei rhodesiense 10, 11, 876, 877. Antitrypanosomal, Trypanosoma brucei selective 180, 181. Antitrypanosomal, Trypanosoma brucei subsp. rhodesiense 852. Antitrypanosomal, Trypanosoma cruzi 10, 11, 876, 877. Antituberculosis 490.

463

Antituberculosis, Mycobacterium tuberculosis 616, 903, 906, 907, 915, 916, 917, 919, 929, 930. Antituberculosis, Mycobacterium tuberculosis H37Rv 483, 866, 897, 899, 904, 905, 913, 920, 921, 922, 933, 934. Antiviral 6, 71, 86, 105, 468, 507, 736, 777, 832, 839, 971, 1024. Antiviral inactive, HSV-2 200, 201. Antiviral, anti-HIV, selective, agent by blocking R5-tropic viruses, without having effects on X4-tropic HIV-1 infection 786. Antiviral, HN/1222H3N2 998. Antiviral, HSV-1 827, 828, 829, 830, 831, 833, 834, 835, 836, 837, 838, 842, 843. Antiviral, HSV-1 complete inhibition with diffuse cytotoxicity 87. Antiviral, HSV-1 corona virus A-59 776. Antiviral, HSV-1 Vesicular stomatitis virus 776. Antiviral, HSV-1, complete inhibition with diffuse cytotoxicity 9, 84. Antiviral, HSV-2 731, 903. Antiviral, IFV H1N1 1087, 1088. Antiviral, induces early antigen of Epstein-Barr virus 1039. Antiviral, influenza A H1N1 594, 595, 596, 1061, 1062, 1063, 1064, 1065, 1067, 1069, 1072, 1073, 1075, 1077. Antiviral, influenza A/WSN/33 virus 998. Antiviral, inhibits growth of feline leukaemia virus 283. Antiviral, inhibits H1N1 virus in infected MDCK cells 622, 623. Antiviral, inhibits hepatitis B virus 100, 101, 102. Antiviral, inhibits replication of feline leukaemia virus 738. Antiviral, LN/1109 H1N1 998. Antiviral, virus Polio sp. 543. Antiviral/cytotoxic, BSC 857, 879. Antiviral/cytotoxic, HSV-1 virus grown on BSC 857, 879. Antiviral/cytotoxic, PV-1 grown on BSC 857, 879. Apomorphine antagonist 573. Apoptosis inducer 579, 581. Apoptosis-inducing activity 96, 97, 98, 99, 95.

464

Index 5 Compound Pharmacological Activity Index

Arrested cell cycle G2/M phase 810. Aspartic protease BACE1 inhibitor, inhibited BACE1-mediated cleavage of amyloid precursor protein 476. ATP binding, in GSK-3β kinase inhibitor, specific non-competitive 917. ATP citrate lyase inhibitor 315. ATPase stimulant used as biochemical tool in study of muscular contraction 839. B Bastadin 5 stimulates release of Ca2+ from SR by binding to RyR1-FKBP12 Ca2+ channel 249. Bengamides activity may be due to inhibition of a novel target 184. Bioluminescent substance 60. Biosynthetic intermed. of teleocidins 1039. C Ca2+ antagonist 9, 84. Ca2+ channel agonist, sarcoplasmic reticulum 262, 279, 314. Ca2+-channel agonist, sarcoplasmic reticulum SR 249. Calcium channel modulator 261. Calmodulin antagonist 821, 823, 889. Cannabinoid receptor CB2 antagonist 1068. Cannabinomimetics, decreasing forskolininduced cAMP accumulation 161. Carboxypeptidase A inhibitor 182. Cardiotonic 227. Cardiotoxic 230, 231, 232. Causal agent of paralytic shellfish poisoning, extremely toxic among most toxic substances known 120. causal agent of shellfish poisoning 117. Causes dermatitis 1041. CD45 phosphatase inhibitor 574. CD45 plays central signaling roles by dephosphorylating Src-kinases and therefore represents an attractive drug target 574. CDK4 inhibitor 486. CDK4 inhibitor, selective 852. Cell cycle inhibitor 15. Cell cycle progression inhibitor 803. Cell division inhibitor, fertilised sea urchin eggs 405, 406.

Cell division Inhibitor, fertilized urchin eggs 717. Cell growth inhibitor 9, 140. Cell-adhesion inhibitor 624, 626. Cell-adhesion inhibitor, EL-4, inhibiting ‘blebbing” in K562 bleb assay 804. Cellular differentiation inducer, HL60 677, 678. Central neurotransmitter and precursor of noradrenaline 227. c-erbB-2 Kinase inhibitor 768. CGRP-binding assay 959. Chemical defence substance 415, 416, 417, 418. Chemokine receptor CXCR4 ligand 36. Chitin synthase inhibitor 573. Chitinase inhibitor 457, 475, 515. Cholesteryl ester synthesis inhibitor 641. Cleaves both single- and double-standed RNA 633. CNS depressant 775. CNS stimulant 698. COMPARE analyses were negative 184. Could reverse multidrug resistance of K562/ A02, MCF7/Adr and KB/VCR cells 1100. CSF inducer 1039. Cyclin dependent kinase 4 inhibitor 927. Cyclin dependent Kinases CDK inhibitor, CDK1/ cyclin B, good selectivity 482. Cyclin dependent Kinases CDK inhibitor, CDK2/ cyclin A, good selectivity 482. Cyclin dependent Kinases CDK inhibitor, CDK2/ cyclin E, good selectivity 482. Cyclin dependent Kinases CDK inhibitor, CDK5/ p25, good selectivity 482. Cyclin dependent Kinases CDK inhibitor, creatine kinase 1 CK1, good selectivity 482. Cyclin dependent Kinases CDK inhibitor, glycogen synthase kinase 3 GSK-3, good selectivity 482. Cysteine proteases inhibitor, Cathepsin B 177, 178. Cysteine proteases inhibitor, Cathepsin L 177, 178. Cysteine proteases inhibitor, Papain 177, 178. Cysteine proteases inhibitor, papain, Cathepsin B and Cathepsin L 7. Cytolytic, fertilized sea urchin eggs 25.

Index 5 Compound Pharmacological Activity Index

Cytolytic, rbt erythrocytes 25. Cytotoxic 5, 50, 82, 86, 91, 168, 226, 278, 280, 285, 286, 412, 420, 434, 435, 436, 437, 447, 456, 576, 579, 580, 581, 597, 598, 599, 684, 685, 686, 687, 688, 689, 734, 742, 765, 796, 798, 812, 852, 866, 890, 913, 915, 916, 971, 994, 1024, 1134. Cytotoxic inactive, A549 83, 860, 861, 1005, 1006, 1007, 1028, 1029, 1057. Cytotoxic inactive, ACC-MESO-1 1040. Cytotoxic inactive, Bel7402 759, 760, 1005, 1057. Cytotoxic inactive, C6 703, 704, 1162. Cytotoxic inactive, CaCo-2 36, 37, 427. Cytotoxic inactive, CHO-K1 189, 196. Cytotoxic inactive, CNE2 759, 760. Cytotoxic inactive, DU145 334. Cytotoxic inactive, H460 334, 473. Cytotoxic inactive, H9c2 427, 703, 704, 1162. Cytotoxic inactive, HCT15 196, 197, 277, 288. Cytotoxic inactive, HCT116 390, 392, 422. Cytotoxic inactive, HeLa 148, 276, 334, 427, 703, 704, 779, 896, 1026, 1040, 1112, 1113, 1146, 1147, 1148, 1160, 1162. Cytotoxic inactive, Hep2 276. Cytotoxic inactive, HepG2 334. Cytotoxic inactive, HL60 173, 1004, 1005, 1006, 1007, 1028, 1029, 1057. Cytotoxic inactive, HT1080 759, 760. Cytotoxic inactive, HT29 83, 196, 373, 374, 861. Cytotoxic inactive, K562 148, 208, 1098, 1146, 1147, 1148. Cytotoxic inactive, KB 225, 313, 924, 925, 936, 937, 1157. Cytotoxic inactive, KM20L2 473. Cytotoxic inactive, L1210 510, 735, 1112, 1113, 1157. Cytotoxic inactive, LoVo 276. Cytotoxic inactive, MALME-3 196, 197. Cytotoxic inactive, MCF7 196, 276, 334, 656, 658. Cytotoxic inactive, MDA-MB-231 334, 860, 861. Cytotoxic inactive, MDR cell line MCF7/Adr 1100. Cytotoxic inactive, MEL28 373.

465

Cytotoxic inactive, Molt4 1005, 1057. Cytotoxic inactive, mouse peritoneal macrophages 856. Cytotoxic inactive, NCI-H460 656, 658, 1026, 1109. Cytotoxic inactive, NSCLC HOP-92 196, 197. Cytotoxic inactive, OVCAR-3 873. Cytotoxic inactive, P388 134, 219, 243, 577, 587, 588, 642, 644, 645, 646, 818, 855, 903, 974, 1160. Cytotoxic inactive, PS 713. Cytotoxic inactive, RD 276. Cytotoxic inactive, SF268 196, 656, 658. Cytotoxic inactive, SNB75 196, 197. Cytotoxic inactive, SW480 464. Cytotoxic inactive, SW1990 334. Cytotoxic inactive, WHCO5 1146. Cytotoxic inactive, WHCO6 1146. Cytotoxic inactive, X-17 276. Cytotoxic, 36 different hmn cell lines 256. Cytotoxic, 3T3-L1 36, 37, 427, 444. Cytotoxic, 786-0 184, 185, 194. Cytotoxic, A2058 18, 19, 20. Cytotoxic, A2780 240, 307, 308, 1121, 1122. Cytotoxic, A2780/DDP 1121, 1122. Cytotoxic, A2780/Tax 1121, 1122. Cytotoxic, A375 218. Cytotoxic, A498 473. Cytotoxic, A549 55, 56, 57, 58, 88, 89, 90, 103, 104, 158, 159, 164, 184, 185, 194, 241, 242, 243, 268, 269, 272, 274, 277, 287, 288, 289, 290, 293, 311, 354, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 508, 577, 641, 642, 644, 645, 646, 647, 648, 649, 650, 652, 653, 654, 657, 667, 681, 682, 714, 724, 738, 752, 753, 776, 781, 789, 792, 793, 794, 799, 802, 804, 805, 859, 875, 880, 881, 887, 1004, 1017, 1026, 1027, 1032, 1033, 1034, 1035, 1036, 1037, 1046, 1097, 1108, 1119, 1120, 1135, 1159. Cytotoxic, anti-oesophageal cancers 1146. Cytotoxic, antiproliferative selectively 858. Cytotoxic, B16 743, 771, 772, 773. Cytotoxic, B16-F-10 875. Cytotoxic, BC-1 643. Cytotoxic, Bel7402 789, 792, 793, 794, 1004, 1027, 1046.

466

Index 5 Compound Pharmacological Activity Index

Cytotoxic, biological activity of extract of Psammoclemma sp. is due to Cytotoxic, psammaplysenes C and D and not P2X7specific activity. 296, 297. Cytotoxic, BSC-1 542, 543. Cytotoxic, BSY1 140. Cytotoxic, BXPC3 184, 917, 997. Cytotoxic, C6 36, 37, 427, 444. Cytotoxic, CaCo-2 444. Cytotoxic, CCRF-CEM 184, 185, 194, 771, 772, 773. Cytotoxic, CEM 164. Cytotoxic, CHO-K1 184, 192. Cytotoxic, CNXF-SF268, selective 265. Cytotoxic, Colon205 184, 185, 194, 871, 872, 873. Cytotoxic, cortical neurons, almost complete cell death 9. Cytotoxic, differentiation of HL60 676, 679. Cytotoxic, DLD-1 810. Cytotoxic, DU145 184, 681, 682, 781, 917, 997, 1026. Cytotoxic, EAC 1116, 1117. Cytotoxic, EMT-6 531. Cytotoxic, excellent leukemia selective 988. Cytotoxic, five tumour cells 1089. Cytotoxic, H460 184, 189, 192, 196, 561, 562, 563, 771, 772, 773. Cytotoxic, H9c2 36, 37, 444. Cytotoxic, HCT8 776, 800, 801, 803. Cytotoxic, HCT15 184, 185, 194, 268, 269, 272, 274, 287, 289, 290, 293, 311. Cytotoxic, HCT116 169, 184, 185, 194, 196, 196, 197, 270, 388, 389, 391, 421, 423, 424, 425, 426, 714, 880, 881, 882, 883, 884, 885, 887, 982, 1121, 1122. Cytotoxic, HCT116/mdr+ 1121, 1122. Cytotoxic, HCT116/topo 1121, 1122. Cytotoxic, HEK-293 8. Cytotoxic, HeLa 36, 37, 75, 80, 95, 103, 105, 213, 242, 282, 444, 564, 565, 566, 567, 568, 569, 681, 682, 805, 805, 810, 893, 894, 895, 917, 969, 1114. Cytotoxic, HeLa-APL 681, 682. Cytotoxic, HeLa-S3 183, 220, 284. Cytotoxic, HepG2 771, 772, 773, 778, 1026, 1136, 1138. Cytotoxic, HEY 577.

Cytotoxic, HL60 95, 96, 97, 98, 99, 202, 203, 204, 603, 604, 605, 606, 634, 677, 678, 779, 789, 792, 793, 794, 805, 810, 1026, 1027, 1046, 1097, 1108. Cytotoxic, HL60, mixture of 7-Oxo-2/3hydroxystaurosporine 800, 801, 803. Cytotoxic, HM02 1136, 1138. Cytotoxic, HMEC1 681, 682, 977. Cytotoxic, hmn carcinoma cell line, P-gp-overexpression variant doxorubicin 398, 399, 400, 401, 402, 403. Cytotoxic, hmn colon carcinoma 912. Cytotoxic, hmn lung carcinoma 912. Cytotoxic, hmn lymphoblastoid namalva cell lines 144. Cytotoxic, hmn melanoma cell lines 472. Cytotoxic, hmn solid carcinoma cell lines 31, 32, 33. Cytotoxic, hmn tumour cell lines 51, 52, 53. Cytotoxic, HOP-92 184, 185, 194. Cytotoxic, HT29 55, 56, 57, 58, 88, 89, 90, 103, 104, 158, 159, 184, 189, 192, 241, 242, 243, 354, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 681, 682, 725, 727, 752, 753, 781, 799, 802, 859, 860, 875, 1017, 1032, 1033, 1034, 1035, 1036, 1037, 1135, 1159. Cytotoxic, Huh7 1136, 1138. Cytotoxic, IGROV 681, 682. Cytotoxic, IGROV-ET 681, 682. Cytotoxic, JB6 CI41 95. Cytotoxic, JurKat 164. Cytotoxic, JurKat, mixture of 7-Oxo-2/3hydroxystaurosporine 800, 801, 803. Cytotoxic, K562 173, 218, 218, 240, 307, 308, 681, 682, 699, 792, 793, 794, 977, 1023, 1098, 1100, 1126, 1147, 1148. Cytotoxic, K562, mixture of 7-Oxo-2/3hydroxystaurosporine 800, 801. Cytotoxic, KB 41, 200, 201, 222, 223, 224, 241, 242, 243, 281, 300, 312, 324, 325, 419, 446, 545, 546, 547, 548, 549, 582, 643, 731, 746, 795, 808, 813, 814, 815, 816, 820, 826, 891, 898, 899, 901, 905, 908, 909, 910, 917, 923, 926, 938, 1100, 1158. Cytotoxic, KB/VJ-300 vincristine-resistant 225. Cytotoxic, KM20L2 184, 917, 997. Cytotoxic, KYSE70 1146.

Index 5 Compound Pharmacological Activity Index

Cytotoxic, KYSE180 1146. Cytotoxic, KYSE520 1146. Cytotoxic, L1210 9, 42, 72, 74, 84, 87, 222, 223, 224, 300, 312, 313, 324, 325, 339, 343, 459, 511, 512, 545, 546, 547, 548, 549, 572, 582, 746, 822, 822, 823, 824, 825, 826, 852, 898, 899, 901, 905, 908, 909, 910, 914, 923, 924, 925, 927, 938, 1128, 1154, 1158. Cytotoxic, L5178 897, 900, 918. Cytotoxic, L5178Y 335, 336, 337, 338, 455, 822, 823, 824. Cytotoxic, L-6 10, 11, 852, 856, 876, 877. Cytotoxic, LNCaP 681, 682, 878, 886, 977, 1121, 1122. Cytotoxic, LoVo 200, 201, 577, 681, 682, 731, 795, 977. Cytotoxic, LoVo-DOX 681, 682, 977. Cytotoxic, LOX 196, 196, 197, 871, 872, 873. Cytotoxic, LOX-IMVI 184, 185, 194. Cytotoxic, LX-1 1121, 1122. Cytotoxic, LXFA-629L, selective 265. Cytotoxic, M21 164. Cytotoxic, MALME-3M 184, 185, 194. Cytotoxic, MAXF-401NL, selective 265. Cytotoxic, MCF7 184, 189, 192, 577, 797, 917, 1100, 1121, 1122, 1159. Cytotoxic, MCF7 and MDA-MB-231 1060. Cytotoxic, MCF12 1146. Cytotoxic, MDA-MB-231 15, 55, 56, 57, 58, 63, 83, 88, 89, 103, 104, 158, 159, 799, 802, 810, 859, 1026, 1032, 1033, 1034, 1035, 1036, 1037. Cytotoxic, MDA-MB-435, mixture of 7-Oxo-2/3hydroxystaurosporine 800, 801, 803. Cytotoxic, MDR cell line K562/A02 1100. Cytotoxic, MDR cell line KB/VCR 1100. Cytotoxic, MEL28 354, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 374, 781, 1135. Cytotoxic, MEXF-276L, selective 265. Cytotoxic, MKN7 140. Cytotoxic, Molt4 164, 871, 872, 873, 1004, 1027, 1046. Cytotoxic, Molt4, mixture of 7-Oxo-2/3hydroxystaurosporine 800, 801, 803. Cytotoxic, MPM ACC-MESO-1 629, 630. Cytotoxic, murine lymphocytes 508. Cytotoxic, NBT-T2 1. Cytotoxic, NCI-H460 184, 917, 997.

467

Cytotoxic, NCI-H522 184, 185, 194. Cytotoxic, neuro-2a 164, 228, 561, 562, 563, 965. Cytotoxic, NFF 878, 886. Cytotoxic, NSCLC A549 196, 196, 197. Cytotoxic, OVCAR-3 184, 184, 185, 194, 196, 196, 197, 473, 871, 872, 997. Cytotoxic, OVCAR-8 184, 185, 194. Cytotoxic, P388 42, 51, 53, 54, 105, 140, 184, 202, 203, 204, 222, 223, 224, 233, 234, 241, 242, 252, 253, 273, 324, 325, 350, 354, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 467, 482, 508, 545, 546, 547, 548, 549, 582, 584, 590, 591, 592, 608, 609, 610, 611, 641, 659, 660, 661, 662, 663, 664, 665, 666, 725, 727, 738, 752, 753, 762, 763, 764, 776, 781, 789, 804, 805, 826, 875, 879, 898, 901, 904, 917, 917, 932, 936, 937, 938, 971, 995, 996, 997, 1017, 1022, 1099, 1102, 1103, 1105, 1119, 1120, 248, 857. Cytotoxic, P388, marked biological activity is still expected based on reactivity of the thioester moiety 555. Cytotoxic, P388, mixture with Kottamide B 973. Cytotoxic, P388, mixture with Kottamide C 972. Cytotoxic, PANC1 681, 682, 977. Cytotoxic, panel of 10 hmn tumour cell lines, 5 active, 5 inactive 197. Cytotoxic, panel of 12 tumour cell lines 544. Cytotoxic, panel of 14 different tumour cell lines 699. Cytotoxic, panel of 14 different tumour cell lines, GI50 values within micromolar range 977. Cytotoxic, panel of 19 tumour cell lines 1090. Cytotoxic, panel of 36 different hmn cell lines, five cell lines with selective activities 265. Cytotoxic, panel of 36 different hmn cell lines, mean IC50 = 0.7 μg/mL 250. Cytotoxic, panel of 36 different hmn cell lines, mean IC50 = 1.8 μg/mL 265. Cytotoxic, panel of 36 different hmn cell lines, mean IC50 = 2.2 μg/mL 249. Cytotoxic, panel of 36 different hmn cell lines, mean IC50 = 2.4 μg/mL 257. Cytotoxic, panel of 36 different hmn cell lines, mean IC50 = 2.9 μg/mL 248.

468

Index 5 Compound Pharmacological Activity Index

Cytotoxic, panel of 36 different hmn cell lines, mean IC50 = 3.2 μg/mL 251. Cytotoxic, panel of 36 different hmn cell lines, mean IC50 = 8.7 μg/mL 263. Cytotoxic, panel of 36 hmn tumour cell lines, mean IC50 = 5.5 μg/mL; 10 μg/mL, 33 active, 3 inactive 1066. Cytotoxic, panel of 37 cell lines, mean IC50 = 0.016 μg/mL, mean IC70 = 0.171 μg/mL, mean IC90 = 2.35 μg/mL, total selectivity = 10/37, Selectivity = 27% 791. Cytotoxic, panel of assays 786, 787. Cytotoxic, panel of hmn tumour cell lines 196. Cytotoxic, panel of hmn tumours HTCLs, moderate 625. Cytotoxic, panel of NCI’s 60 cell lines, broad cytotoxicity with considerable selectivity against melanoma and leukemia cell lines 421. Cytotoxic, panel of NCI’s cell lines, mean GI50 = 15.1 μmol/L 971. Cytotoxic, panel of NCI’s Development Therapeutics Program 60 cell lines, mean IC50 = (0.011±0.001)μmol/L 185. Cytotoxic, panel of NCI’s Development Therapeutics Program 60 cell lines, mean IC50 = (2.70±0.23)μmol/L 194. Cytotoxic, panel of NCI’s Development Therapeutics Program, mean IC50 = (0.046±0.005)μmol/L 184. Cytotoxic, panel of NCI’s hmn tumour cell lines, mean GI50 = 1.8 μmol/L 857. Cytotoxic, PBMC, mixture of 7-Oxo-2/3hydroxystaurosporine 800, 801, 803. Cytotoxic, PC3 244, 1121, 1122. Cytotoxic, PRXF-22RV1, selective 265. Cytotoxic, RKO 214, 215. Cytotoxic, SCHABEL 354, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374. Cytotoxic, selective 170, 635. Cytotoxic, several hmn tumour cell lines, weak 700. Cytotoxic, several HTCLs cells 640, 655. Cytotoxic, SF268 184, 189, 192, 917. Cytotoxic, SF295 184, 473, 997. Cytotoxic, SF295, mixture of 7-Oxo-2/3hydroxystaurosporine 800, 801, 803.

Cytotoxic, SGC7901 778. Cytotoxic, SKBR3 681, 682, 1121, 1122. Cytotoxic, SK-MEL-2 268, 269, 272, 274, 277, 287, 288, 289, 290, 293, 311. Cytotoxic, SK-MEL-5 473. Cytotoxic, SK-MEL-28 681, 682, 810. Cytotoxic, SK-OV-3 268, 269, 272, 274, 277, 287, 288, 289, 290, 293, 311, 681, 682. Cytotoxic, SNB19 184, 185, 194, 196, 196, 197. Cytotoxic, SNB75 184, 185, 194. Cytotoxic, SNU-C4 810. Cytotoxic, strong 790. Cytotoxic, Sup-T1 250, 256, 258, 259, 260, 261, 264. Cytotoxic, T47D 776. Cytotoxic, THP-1 95, 810. Cytotoxic, tsFT210 789. Cytotoxic, U266 164. Cytotoxic, U373 577. Cytotoxic, U937 225. Cytotoxic, UACC62 184, 185, 194. Cytotoxic, UO-31 184, 185, 194, 196, 196, 197. Cytotoxic, UT7 1147, 1148. Cytotoxic, variety of tumour cells 651. Cytotoxic, various potent anticancer props 761. Cytotoxic, Vero 77, 819, 917. Cytotoxic, weak 1025, 1130, 1150. Cytotoxic, WHCO1 1146. Cytotoxic, XF498 268, 269, 272, 274, 277, 287, 288, 289, 290, 293, 311. Cytotoxic/Antiviral, BSC-1infected with RNA virus PV1 971. D Defensive secretion 521. Dehydrofolate reductase inhibitor 258. Diuretic, used for treatment of dysentery 229. DNA binder, chromatographic purification procedure 844, 865. DNA binding agent 434, 435, 436, 437, 438, 439. DNA methyltransferase inhibitor 268, 292. DNA polymerase α inhibitor, calf thymus 135, 136. DNA polymerases inhibitor, mammalian 554. DNA topoisomerase II inhibitor 554.

Index 5 Compound Pharmacological Activity Index

E EGFR inhibitor 517, 518. Elastase inhibitor 394. Endothelin A receptor inhibitor 315. Endothelin agonist 803. Endothelin converting enzyme inhibitor 910. Enzyme inhibitor 855. Esterases inhibitor 394.

469

G Galanin-binding assay with a hmn cell line BOWES 959. Gives Gmelin reaction with conc. HNO3/CHCl3 522. Glucanase inhibitor 470. Glutathione reductase inhibitor 278, 286. Glycine-binding assay, regulatory site of NMDA receptor 959. G-protein coupled receptor 18 [N-arachidonyl glycine receptor] antagonist 1074. Growth inhibitor 540, 541.

375, 376, 377, 378, 381, 382, 383, 384, 385, 386, 387, 395. HIF-1 activation inhibitor, T47D cell-based HIF-1 activation reporter assay, suppressed mitochondrial respiration by blocking NADH-ubiquinone oxidoreductase 379, 380. Highly potent toxin, non-protein, low molecular weight potent neurotoxin responsible for many hmn intoxications and fatalities each year 108. Highly toxic, mammals, birds, reptiles, amphibians and fish 108. Histamine antagonist 952. Histamine-H3 antagonist 1127. Histone deacetylase inhibitor 268, 291. HIV-1 fusion inhibitor 85. HIV-1 integrase inhibitor, HIV encodes three enzymes, reverse transcrptase RT, protease PR and integrase IN 411. HIV-1 protease inhibitor 662, 663, 664, 665, 666. HIV-1-rt inhibitor 852. HIVgp-120-hmn CD4 binding inhibitor 76, 77, 78. HLE inhibitor 1089, 1090. HLE is a primary source of tissue damage with inflammatory diseases such as chronic obstructive pulmonary disease, cystic fibrosis, and adult respiratory distress syndrome 1089, 1090. Hypoglycemic, AGE formation inhibition 528, 529. Hypoglycemic, aldose reductase inhibitor, RLAR 528, 529. Hypotensive 803.

H H/K-ATPase inhibitor 42. H/K-ATPase is a gastric proton pump of stomach and is enzyme primarily responsible for acidification of stomach contents 42. Haemolytic 2. Hallucinogen 855. HIF-1 activation inhibitor, T47D cell-based HIF-1 activation reporter assay, suppressed mitochondrial respiration 340, 349, 352, 353, 355, 356, 357, 358, 359, 360, 361, 362,

I Ichthyotoxic 92, 509, 1048, 1049, 1154. Ichthyotoxic, goldfish 228, 965. Ichthyotoxin 9, 25, 84, 777, 1050, 1051, 1053, 1055. Ichthyotoxin, most ichthyotoxic of antarctic 62. IDO inhibitor 1000, 1001, 1002. IDO is an molecular target for treating cancer involved in immune escape 1000. IL-8 Rα receptor inhibitor 484, 486, 506. IL-8 Rα receptor inhibitor inactive 483, 485.

F Factor XIIIa inhibitor 218. Farnesyl-protein transferase inhibitor 268. Fe-chelating activity 46, 47. Fibroblast inhibitor 641. First USP7 inhibitor from a natural source 466. Food preservative 997. FOXO1a is a downstream target of the PTEN tumor suppressor, psammaplysene A compensates for PTEN loss by relocalizing the transcription factor FOXO1a to the nucleus 294. FOXO1a nuclear export inhibitor 294. FOXO1a nuclear export inhibitor, specific 295.

470

Index 5 Compound Pharmacological Activity Index

IL-8 Rβ receptor inhibitor 483, 484, 485, 486, 506. Immune system activity, IL-8 inhibitor, MMOA: AP-1 transcription factor inhibition 526. Immune system activity, macrophage iNOS inhibitor, MMOA: - NF-κB transcription factor inhibition 530. Immunomodulator 397, 404, 408, 409, 410. Immunostimulatory 629. Immunosuppressant 456, 662, 663, 664, 665, 666. Immunosuppressant, LCV 911. Immunosuppressant, MLR 911. Immunosuppressive 344. Immunosuppressive, B lymphocytes reaction assay 862. Immunosuppressive, mixed lymphocyte reaction assay 508. IN inhibitor, terminate cleavage activity 411. Inducer of apoptosis, HL60 cells 1082, 1084. Induces apoptosis, HL60 1027, 1078, 1081, 1083. Induces apoptosis, MCF7 1105. Induces apoptosis, transformed mammalian cells 1147, 1148. Induces Ca2+ release from sarcoplasmic reticulum, 10 times more potent than caffeine 824. Induces change of characteristics of the differentiation, such as growth arrest, adhesiveness to culture plate, phagocytosis of latex particles 676. Induces early apoptosis, THP-1 95. Induces large intracellular vacuoles, rat 3Y1 fibroblasts 608, 609, 610, 611, 612, 613, 614, 615. Induces metamorphosis in ascidian larvae 65, 66. Induces substance P release, from dorsal root ganglia neurons via PKC pathway 1096. Induction of apoptotic phenomena 51, 52, 53. Inflammatory 155, 156. Inflammatory and vesicatory 1041. Inflammatory, enhancer of phosphorylation with PKC in presence of Ca2+ and TPA 131. Inhibited TPA-induced superoxide anion generation 579, 580, 581.

Inhibitor of accumulation of cholesterol ester in macrophages 893, 894, 895, 896, 917. Inhibitor of aromatase P450 757. Inhibitor of cathepsin K 757. Inhibitor of cell migration 36. Inhibitor of chitinase 287. Inhibitor of C-X-C motif chemokine 12-induced DNA synthesis 36. Inhibitor of cytochrome P450 3A4 757. Inhibitor of DNA methyltransferase 287. Inhibitor of dopamine transporter DAT 36, 37. Inhibitor of extracellular-signal-regulated kinases ERK1/2 activation 36. Inhibitor of farnesyl protein transferase 287. Inhibitor of histone deacetylase 287, 757. Inhibitor of large-conductance Calciumactivated Potassium channels 1078, 1081, 1083, 1085. Inhibitor of leucine aminopeptidase 287. Inhibitor of multidrug resistance factor P-glycoprotein 999. Inhibitor of neuronal nitric oxide synthase 14, 15, 17. Inhibitor of protein kinase 757. Inhibitor of pyruvate phosphate dikinase PPDK 14, 15. Inhibitor of serine/threonine kinase Aurora A, involved in cell division regulation 683, 854. Inhibitor of topoisomerase II 757. Inhibitor of ubiquitin-activating enzyme E1 863, 864. Inhibitors of topoisomerase II, cathepsin K, cytochrome P450 3A4, aromatase P450, protein kinase and histone deacetylase, potent 772, 773. Inhibits accumulation of cholesterol esters in macrophages 892. Inhibits binding of HIVgp-120 to CD4 75. Inhibits biofilm formation 953. Inhibits biofilm formation, Candida albicans 1081, 1083. Inhibits calcineurin 1119, 1120. Inhibits cell division, fertilized sea urchin eggs 225. Inhibits cell proliferation 1022.

Index 5 Compound Pharmacological Activity Index

Inhibits competitively banding of von Willebrand facter to GPIb/IX receptors 136. Inhibits EGF-induced malignant transformation of JB6 P+ Cl 41 cells 1083. Inhibits EGF-induced malignant transformation, JB6 P+ CI41, potential cancer preventive effect 1084. Inhibits growth of marine bacteria but doesn‘t affect terrestrial species 146. Inhibits growth of Mycobacterium tuberculosis H37Rv 490. Inhibits interleukin-1 stimulated rheumatoid synovial fibroblasts 482. Inhibits larval settlement and metamorphosis 39. Inhibits lipopolysaccharide LPS-induced nitric oxide production, BV2 microglial 992, 993. Inhibits macrophagic NO synthase induced by LPS 70. Inhibits microtubule assembly 639. Inhibits MT1-matrix metalloproteinase 583. Inhibits proliferation of LNCaP cells G2 phase 15. Inhibits proliferation of spleen cells, mus, lymphocyte B LPS-induced 446. Inhibits proliferation of spleen cells, mus, lymphocyte T ConA-induced 446. Inhibits response to inflammation promoting agents fMLP and PMA 974. Inhibits secretion of virulence factor Yersinia Outer Protein E 38. Inhibits settlement of barnacle larvae 1127. Inhibits superoxide production 974. Inosine 5′-phosphate dehydrogenase inhibitor 254. Insecticidal, beet armyworm Spodoptera exigua 138, 139. Insecticidal, Carpophilus hemipterus 1079, 1080. Insecticidal, Helicoverpa zea 1079, 1080. Insecticidal, Helicoverpa zea, Carpophilus hemipterus and Spodoptera frugiperda 1078. Insecticidal, Spodoptera frugiperda 1079, 1080.

471

Insecticide 447, 448, 467, 482, 550, 556, 557, 558, 570, 784, 917, 1052, 1073, 1161. Insecticide, larvae of beet army worm Spodoptera exigua and corn rootworm Diabrotica undecimpunctata 446. Insecticide, larvicide 1118. Interleukin binding inhibitor 76. Intermedium in metabolism of cysteine 4. Ionotropic glutamate receptor agonist 550. Isoprenylcysteine carboxyl methyltransferase inhibitor 221. K Kinase c-erbB-2 inhibitor 513, 514, 517, 518. Kynurenine-3-hydroxylase inhibitor, selective 327. L L-1R antagonist 218. Larval metamorphosis-promoting activity 345. Larvicide 523. LC50 447. LC50 brine shrimp 589. LD medaka cells Oryzias latipes 25. LD mus ip 25. LD50 157. LD50 brine shrimp 1070. LD50 brine shrimp Artemia salina 228, 965. LD50 goldfish 228, 965. LD50 mice ip 508. LD50 mus 550. LD50 mus ip 1123. LD50 mus ipr 106, 108, 110, 119, 120, 394, 553, 723, 1003, 1076, 1125. LD50 mus ivn 108, 120, 394. LD50 mus orl 108, 1041. LD50 mus scu 4, 394. LD50 rat ipr 227. LD50 rat orl 120. LD99 Bacillus subtilitis 147. LD99 mus ip 236, 237. Less well efficiently for azidopine binding site on P-glycoprotein than did verapamil 531. Leucine aminopeptidase inhibitor 268. Leukotriene B4 receptor antagonist 1140, 1141.

472

Index 5 Compound Pharmacological Activity Index

Leukotriene B4 receptor binding activity 1140, 1141. Leukotriene B4 receptor binding activity, hmn whole U937 cell receptor binding assay, high affinity 1141. Lipid droplet formation inhibitor 641. M MAP kinase kinase MEK inhibitor 467, 482. MDR inhibitor 397, 407. MDR reversing agent 419. Mediated by caspase-8, caspase-9, caspase-3dependent apoptosis 810. Melanogenesis inhibitor 637. Metabolic regulator 4. MMP-2 inhibitor 584. Modulator of Staphylococcus aureus virulence gene expression 34. Molluscacidal, marine snail Biomphalaria glabrata 393. Monoamine oxidase inhibitor 573, 1030. MT1-MMP inhibitor 584, 585, 586. Multidrug resistance reversing agent, more efficiently for azidopine binding site on Pglycoprotein than verapamil 537. Multidrug resistance reversing agents 531. Multidrug resistance reversing agents, less well efficiently for azidopine binding site on Pglycoprotein than verapamil 532, 533, 536. Multidrug resistance reversing agents, more efficiently for azidopine binding site on Pglycoprotein than verapamil 534, 538. Multidrug resistance reversing agents, very poorly efficiently for azidopine binding site on P-glycoprotein than verapamil 535, 539. Muscle relaxant 982, 983. Mycothiol S-conjugate amidase inhibitor 35. Mycotoxin 1104. N Na/K-ATPase inhibitor 235, 301, 1143, 1144, 1145, 1154, 1155, 1156. Na1+ channel blocker, producing approximately half the response of saxitoxin 561, 562, 563. Na1+ ion blocker 106. Nematocide 186, 187, 197, 207, 573, 601, 803, 1041, 1133.

Nerve growth factor 573. Nervous system activity, inhibits of serotonin receptor binding, MMOA: - Ca2+ influx inhibition 341, 342. Nervous system activity, neurite outgrowth inducer, MMOA: - MAP kinase activation, promotes differentiation of PC12 cells 527. Neuraminidase inhibitor 176. Neuritogenic, hmn neuroblastoma cells 554. Neuronal nitric oxide synthase inhibitor, selective 1011, 1012. Neuroprotective agent, against Aβ25–35-, H2O2– and oxygen-glucose deprivation-induced neurotoxicity in SH-SY5Y cells 36, 37. Neuroprotective, against Aβ25–35-induced SHSY5Y cell damage 766, 767. Neurotensin-binding assay, NT 959. Neurotoxic, goldfish toxicity assay 561, 562, 563. Neurotoxin 113, 114, 115, 116, 117, 118, 119, 121, 550, 551, 559, 560, 1003. Neurotoxin, anticholinesterase 1125. Neurotoxin, causal agent, with Saxitoxin of shellfish poisoning 112. Neurotoxin, neuromuscular blocker 119. Neurotropic 803. Neurotoxin 474. NO release inhibitor, LPS-stimulated macrophages 162, 163. O Orycyclin dependent kinase 4 inhibitor 768. Oxygen release inhibitor, neutrophil burst assay 804. P P2X7 receptor inhibitor 432, 433. p56lck Tyrosine kinase inhibitor 852, 856. Paralytic poison 106, 109. Peptidase CPP32 inhibitor 1119. Pesticide 777. Phototherapeutic agent 525. Phycotoxin 106, 109, 110, 729. Phytotoxic 705. PKC activator 1039.

Index 5 Compound Pharmacological Activity Index

PKC activator, in presence of Ca2+, weak activity 155, 156. PKC activator, in presence of TPA, enhanced activity 155, 156. PKC inhibitor 453, 466, 467, 482, 483, 484, 485, 486, 506, 790, 795, 804, 935. PKCs inhibitor inactive, ζ-PKC 804. PKCs inhibitor, seven of eigut cloned PKC isoenzymes: α-PKC, βI-PKC, βII-PKC, δ-PKC, ε-PKC, η-PKC, and γ-PKC 804. PKC-α inhibitor 792, 793, 794. PKs inhibitor, a panel of 24 enzymes 310. PLA2 inhibitor, bee venom PLA2 673, 706, 955, 956, 958, 966, 976. PLA2 inhibitor, selective 212. Plant auxin 723. Plant growth inhibitor 855. Plant growth regulator 673, 698, 729, 989, 990, 991. Platelet aggregation inhibitor 803. Polo-Like kinase-1 inhibitor 467, 482. Potassium-channel blocking activity 982. Potential Antiulcer drug 42. PP2A inhibitor 492, 498, 499. PP2A inhibitor inactive 449, 454, 471, 477, 493, 494, 506. PPAR-γ agonistic activity 690. PPAR-γ agonistic activity, cell-based luciferase reporter assay 691, 692, 693, 694. Prevents metastatic cancer spread 446. Principal odorous component of marine hemichordate Ptychodera flava laysanica 675. Pronounced reversible and non-cytotoxicity effect on mammalian cell morphology 206. Proteases inhibitors inactive, Aspartic protease, Cathepsin D 12, 13, 40, 177, 178. Proteases inhibitors inactive, Metal protease, Thermolysin 12, 13, 40, 177, 178. Proteases inhibitors inactive, Serine proteases, Chymostatin 12, 13, 40, 177, 178. Proteases inhibitors inactive, Serine proteases, Trypsin 12, 13, 40, 177, 178. Proteases inhibitors, Cysteine proteases, Bromelain 12, 13, 40, 177, 178. Proteases inhibitors, Cysteine proteases, Cathepsin B 12, 13, 40, 177, 178.

473

Proteases inhibitors, Cysteine proteases, Cathepsin L 12, 13, 40, 177, 178. Proteases inhibitors, Cysteine proteases, Ficin 12, 13, 40, 177, 178. Proteases inhibitors, Cysteine proteases, Papain 12, 13, 40, 177, 178. Proteasome inhibitor 893, 894, 895, 896, 917, 931. Protein biosynthesis inhibitor 1134. PTK inhibitor 487. PTP1B inhibitor 212. R Receptor binding activity, hmn B2 bradykinin receptor site, inhibition of ligand binding 959, 960, 963, 964. Receptor binding activity, neuropeptide Y receptor site, inhibition of ligand binding 960, 963, 964. Receptor binding activity, somatostatin receptor site, displaced radioactive ligand 960, 963, 964. Receptor binding activity, neuropeptide Y receptor site, inhibition of ligand binding 959. Receptor binding activity, somatostatin receptor site, displaced radioactive ligand 959. Receptors binding inactive, AMPA-binding assay, quisqualate site of glutamate receptor 960, 963, 964. Receptors binding inactive, CGRP-binding assay 960, 963, 964. Receptors binding inactive, galanin-binding assay, with a hmn cell line BOWES 960, 963, 964. Receptors binding inactive, glycine-binding assay, regulatory site of NMDA receptor 960, 963, 964. Receptors binding inactive, neurotensinbinding assay 960, 963, 964. Receptors binding inactive, vasointestinal polypeptide-binding assay 960, 963, 964. Reduced to bilirubin in mammals 522. Reduction of voltage-dependent Ca2+ entry, MMOA: - irreversible effect requiring lipophilic brominated side chain 432, 433. Reverses doxorubicin resistance in MDR Ad300 cells 999.

474

Index 5 Compound Pharmacological Activity Index

Reverses doxorubicin resistance in MDR SW620 cells 999. RyR1-FKBP12 Ca2+ channel is a tetrameric heterodimeric channel protein ~2000 kDa that is associated with the smaller 12 kDa immunophilin FKBP12 249. S Sedative 855. Selective inhibition of hmn leukocyte elastase 1086. Serine protease inhibitor 26, 27, 28, 29, 30. Serotonergic neurotransmission potentiator 1030. Serotonin antagonist 506, 509. Serotonin receptor agonist 959. Serotonin receptor antagonist 463, 483. Sexual differentiation factor 523. Siderophore 44, 45, 46, 47, 165, 209. Siderophore, sensitizes tumour cells to macrophage-mediated cytolysis 198. Skin irritant 1042, 1043. Sleeping sickness 93, 94. Smooth muscle contractant 483. Smooth muscle relaxant 803. Sodium channel blocker 109. Sodium channel blocker, murine Neuro-2a cells 143, 145. Sodium channels [I, II, III and h1] blocker 120. Sodium channels [I, II, III, μ1 and h1] blocker 108. Somatostatin antagonist 449. Somatostatin inhibitor 509. Specifically inhibits blastulation of starfish embryos 583. Sphingosine kinase inhibitor 211, 216, 217. Sympathomimetic 227. T Topoisomerase II inhibitor 258. Topoisomerase II inhibitor, in LNCaP cells 15. Toxic 1123. Toxic, brine shrimp 440, 441, 442, 443, 563, 718, 784, 1139. Toxic, brine shrimp and goldfish 228. Toxic, brine shrimp Artemia franciscana 446, 447. Toxic, brine shrimp Artemia salina 1070, 1071.

Toxic, crab Hemigrapsus sanguineus 48, 319, 320. Toxic, fish and dissociated cell of freshwater sponge Ephydatia fluviatilis 776. Toxic, mus ip 236, 237. Toxin 107, 111, 122, 123. TPA binding inhibitor 1042, 1043. Transactivats PPAR-γ, cell-based luciferase reporter assay 975, 1021. Tremorgenic mycotoxin 775, 1076. TRPA1 inhibitor 67. TRPA1 inhibitor inactive 68, 69. TRPV1 inhibitor 68, 69, 67. TRPV1 inhibitor, a transient receptor potential cationic channel of subfamily V 67. TRPV3 inhibitor 68, 67. TRPV3 inhibitor inactive 69. Tubulin polymerization inhibitor, arrests cell cycle through G2/M phase 1026. Tumour promoter 1039, 1041, 1038. Tyrosine kinase inhibitor 289, 517. U Urokinase inhibitor 394. USP7 inhibitor selective 466. UV-A protecting, exceeded commercially applied sunscreen agent oxybenzone 171, 173. UV-A-protecting, commercially applied sunscreen agent oxybenzone 174. V Vasoactive intestinal peptide inhibitor 509. Vasointestinal polypeptide-binding assay, VIP 959. Vasopressin antagonist 1055. Vasorelaxant 803. Vermifuge 550, 557, 729. Very few compound that demonstrate nmol/L potency for inhibition of either calcineurin or peptidase CPP32 activity 1119, 1120. Very toxic 1041. α α-Adrenoceptor blocker 484. α-Glucosidase inhibitor 888. α1 GlyR antagonist, potent and selective 520. β β-Secretase inhibitor 414.

Index 5 Compound Pharmacological Activity Index

δ δ-Opioid receptor binding affinity, gpg, inhibits binding of opioid peptide [3H]DPDPE 266, 318. δ-Opioid receptor binding affinity, gpg, to displace opioid peptide [3H]DPDPE from δ-opioid receptors in membranes, selective 267.

(The End of HAMNP Volume 3)

475

μ μ-Opioid receptor ligand, selective and potent 36, 37.