Handbook of Active Marine Natural Products: Volume 4 Alkaloids, Part 2 9783110653908, 9783110653625

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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 4: Alkaloids, Part 2

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

ISBN 978-3-11-065362-5 e-ISBN (PDF) 978-3-11-065390-8 e-ISBN (EPUB) 978-3-11-065373-1 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/10.1515/9783110653908-201

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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 4

Oxazolines Thiazoles Thiadiazoles and Triazoles 4.1 Oxazoline Alkaloids 1 4.2 Thiazole and Thiadiazole Alkaloids 52 4.3 Oxazoline-Thiazole Macrocyclic Alkaloids 4.4 Triazole Alkaloids 76

5

Pyridines and Piperidines 5.1 Pyridine Alkaloids 5.2 Piperidine Alkaloids

77 77 104

6

Quinolines Isoquinolines and Quinazolines 6.1 Quinoline Alkaloids 117 6.2 Isoquinoline Alkaloids 163 6.3 Quinazoline Alkaloids 173

7

Pyrimidines and Pyrazines 7.1 Pyrimidines 177 7.2 Pyrazines 189

8

Purines and Pteridines 241 8.1 Purines and Analogues 241 8.2 Pteridines and Analogues 248

9

Sesquiterpene and Sesterterpene Alkaloids 9.1 Sesquiterpene Alkaloids 251 9.2 Sesterterpene Alkaloids 279

117

177

251

1

69

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10 Steroidal and Miscellaneous Alkaloids 10.1 Steroidal Alkaloids 285 10.2 Miscellaneous Alkaloids 303

285

Index 1 Compound Name and Synonym Index 375 Index 2 Compound Molecular Formula Index 388 Index 3 Compound Organism Source Index 408 Index 4 Compound Sampling Geographic Locality Index 415 Index 5 Compound Pharmacological Activity Index 419

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/10.1515/9783110653908-202

Introduction The Handbook of Active Marine Natural Products covers eight volumes, and this book is Volume 4: Terpenoids, Part 2, which includes 979 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 979 for volume 4) 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 A 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 979 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 of 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 atom-bond level, including complicated glycosides, with stereo chemical information based on the data in the original papers. For example, the structure with full stereochemistry of compound 417 Kuanoniamine D is N N S

N H 2'

HN O

https://doi.org/10.1515/9783110653908-203

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

Source Terms The source data of compound 417 Kuanoniamine D is Source: Sponge Oceanapia sp. (Truk, Federated States of Micronesia), ascidian Cystodytes sp. (Fiji), an unidentified ascidian and its predator prosobranch Chelynotus semperi (depth of 25 m, Mante Channel, Pohnpei I., Federated States of Micronesia, Oct 1987). 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 (sampling place, sampling season, water depth, etc.) English-type name + Latin name of source 3 (sampling place, sampling season, water depth, etc.)

Pharmacological Terms The pharmacological terms in the handbooks are presented by a multilayered structure. In the top layer, there are more than 20 types of the 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 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 417 Kuanoniamine D, a set of multiple biodata is presented as follows: Pharm: Cytotoxic (KB, IC50 = 5 μg/mL); cytotoxic (in vitro, HCT, IC50 = 7.8 μmol/L, control etoposide, IC50 = 2.5 μmol/L; XRS-6 cells, IC50 = 88.9 μmol/L, etoposide, IC50 = 0.14 μmol/L, dose-dependent inhibition of proliferation);

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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)

differential cytotoxicity (ratio BR1 IC50/XRS-6 IC50 = 2); topoisomerase II inhibitor (IC90 = 127 μmol/L, control mitoxantrone, IC90 = 1.1 μmol/L); DNA intercalator (K = 62 μmol/L); affinity to adenosine receptors (strong affinity to A1-adenosine receptors, Ki = 2.94 μmol/L, A2-adenosine receptors, Ki = 13.7 μmol/L, benzodiazepine binding sites of GABAA receptors); chelating agent; insecticide (neonate larvae of polyphagous pest insect Spodoptera littoralis, LC50 = 59 ppm); toxic (brine shrimp lethality, LC50 = 19 μg/mL). The format is as follows: Pharm: Term name 1 (formatted detail information)

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Term name 2 (formatted detail information) Term name 3 (formatted detail information) Term name 4 (formatted detail information) Term name 5 (formatted detail information) Term name 6 (formatted detail information) Term name 7 (formatted detail information) Term name 8 (formatted detail information) Term name 9 (formatted detail information) Under the term name Cytotoxic, a set of multiple cytotoxic biodata is presented as follows: Cytotoxic in vitro KB cells, IC50 = 5 μg/mL HCT cells, IC50 = 7.8 μmol/L, control etoposide, IC50 = 2.5 μmol/L; XRS-6 cells, IC50 = 88.9 μmol/L, etoposide, IC50 = 0.14 μmol/L; (dose-dependent inhibition of proliferation). 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); target cancer cell 3, 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, and 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 handbooks. For complete information in volume 4, of all 826 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 bio activities 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 9 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 in 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 following two closed 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 ([email protected]). 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 Bumhamthorpe Road West, Suite 1000 Mississuga, Ontario L5B 3J1, Canada (data collection in 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 early stage) 9 Dr. Xianfeng He, Associate Professor, Scientific Researcher, EMMS Group, State Key Laboratory of Multiphase Complex Systems, Institute of Process Engineering,

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Chinese Academy of Sciences, Beijing 100190, China (data collection in 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 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

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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 kinds 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) Source(s) Type 1

Type 5

Type 2

Type 6

Compound(s)

Type 4

Pharm-activity

Type 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 the volume 4 are isolated from sponges of genus Agelas? From index 3 of volume 4, one will get the following related data in detail: Agelas axifera 483, 484, 485. Agelas clathrodes 177. https://doi.org/10.1515/9783110653908-204

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Agelas conifera 177. Agelas dispar 177, 251, 561, 562. Agelas longissima 177, 561, 562, 649. Agelas nakamurai 645. Agelas oroides 89, 90. Agelas sp. 168, 563. Since all compounds 1–979 in volume 4 are alkaloids, it is these 13 compounds (89, 90, 168, 177, 251, 483, 484, 485, 561, 562, 563, 645, and 649) are answer to the current question. Then, readers can enjoy studying these 13 compounds by reading the book, including their pharm-activity (question of types 3 and 5). For example, with entry 89 Fistularin 3, a reader will know that the compound had already been isolated from the following sponges in genus Agelas: Sponge Aplysina fistularis, Sponge Aplysina archeri, Sponge Agelas oroides, Sponge Pseudoceratina durissima, Sponge Verongula sp., Sponge Verongia aerophoba, Sponge Verongia cavernicola. And Fistularin 3 has the following pharmacological activities: Antiviral (inhibits growth of feline leukemia virus, ED50 = 22 μmol/L). O

O

Br

Br

Br

Br

OH

Br

HO O

H N

N

OH

OH O

O

O H N

N O

Br

Another example is entry 90 11-epi-Fistularin 3. The compound 11-epi-Fistularin 3 had been isolated from sponge Agelas oroides only (Great Barrier Reef, Australia), and it has antibacterial and cytotoxic pharmacological activities (breast cancer cells). O

O Br

Br

Br

Br

OH

Br

HO O

H N

N O

OH

OH O Br

O H N

N O

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(2) An Illustration of Type 4 (and Type 2, Type 6) Question “What are isolated alkaloids in volume 4 with pharmacological activity Topoisomerase inhibitor? And what are their marine sources?” To browse Index 5 of volume 4, searching “Topoisomerase inhibitor,” the following results were obtained: Topoisomerase I inhibitor 369, 713. Topoisomerase II inhibitor 365, 368, 371, 373, 376, 388, 398, 400, 402, 409, 417, 427, 428. Topoisomerase II inhibitor decatenation inhibition assay 337, 363, 366, 367. Topoisomerase II inhibitor inactive decatenation inhibition assay 332, 364, 378. Topoisomerase II inhibitor inactive inhibits catalytic activity of topoisomerase II 389, 390. Topoisomerase II inhibitor catenates DNA 420. Topoisomerase inhibitor 386, 437, 438. Further, from the entry bodies of the 28 compounds (332, 337, 363–369, 371, 373, 376, 378, 386, 388–390, 398, 400, 402, 409, 417, 420, 427, 428, 437, 438, and 713), all their sources can be obtained. Besides one can also get other pharmacological activities they have (see Table 2). In summary, 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.

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

Code Compound Name Structure





Damirone B

O H N

O

N

Other Pharmacological Activities

Related Sources

Cytotoxic (HCT, IC = . μmol/L; XRS-, IC = . μmol/L, HF (hypersensitivity factor) IC BR/IC XRS- = ).

Sponge Zyzzya fuliginosa (Fiji); sponge Damiria sp.

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How to Use the HAMNP Books

Table 2 (continued ) Vol.

Code Compound Name Structure





Discorhabdin A

O

H N

HN

S N Br O





Makaluvamine A

O NH

N

N





H

Varamine A N O N H

S

HN O

Other Pharmacological Activities

Related Sources

Cytotoxic (HCT, IC >  μmol/L; XRS-, IC >  μmol/L; HF (hypersensitivity factor = IC BR/IC XRS- = ); selective anti-protozoal (chloroquine-susceptible Plasmodium falciparum, IC =  nmol/L, CRPF, IC =  nmol/L); antimalarial negative result (murine model in vivo, high levels of toxicity were observed, including weight loss, movement reduction, and dehydration)

Sponge Latrunculia sp. (psychrophilic, cold water, Aleutian Is., coast of Alaska) sponge Zyzzya fuliginosa (Fiji)

Cytotoxic (HCT, IC = . μmol/L; XRS-, IC = . μmol/L; HF (hypersensitivity factor) = IC BR/IC XRS- = ; mechanism of action involving DNA doublestranded breakage, an activity characteristic of topoisomerase I inhibitors); antineoplastic (in vivo dose . mg/kg, hmn ovarian carcinoma OVCAR-, T/C = %; P murine leukemia, only marginal life extension)

Sponge Zyzzya fuliginosa (Fiji); sponge Zyzzya massalis

Cytotoxic (L, IC = . μg/mL);

Ascidian Lissoclinum vareau

How to Use the HAMNP Books

XXIII

Table 2 (continued ) Vol.

Code Compound Name Structure

Other Pharmacological Activities

Related Sources





Cytotoxic (L, IC = . μg/mL)

Ascidian Lissoclinum vareau

Cytotoxic (HCT, IC = . μmol/L, Bel, IC = . μmol/L, A, IC = . μmol/L, A, IC = . μmol/L)

Marine-derived streptomycete Streptomyces sp. CHQ-

Varamine B N O N H

S

HN O





Drimentine G

H N H

O

NH H

H

O

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 cyclindependent 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 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 imprinting 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 methicilline-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 (‒logM) 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, a 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 co-localized 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

XXXIII

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)

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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)

XXXIX

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)

4 Oxazolines Thiazoles Thiadiazoles and Triazoles 4.1 Oxazoline Alkaloids 1 Almazole C Type: Oxazoline alkaloids. C21H21N3O [α]D20 = +166° (c = 1.08, MeOH). Source: An unidentified red alga (family Delesseriaceae, Senegal). Pharm: CNS activity. Ref: I. N’Diaye, et al, Tet. Lett., 1994, 35, 4827│G. Guella, et al, Helv. Chim. Acta, 1994, 77, 1999

N O

N

N H

2 Almazole D Type: Oxazoline alkaloids. C22H21N3O3 Powder, mp 135–139 °C, [α]D23 = +115° (MeOH) (Me ester), [α]D23 = +31° (MeOH) (Na salt). Source: Red alga Haraldiophyllum sp. Pharm: Antibacterial (gram-negative Serratia marcescens and Salmonella typhi). Ref: I. N’Diaye, et al, Tet. Lett., 1996, 37, 3049│F. Miyake, et al, Tetrahedron, 2010, 66, 4888 HOOC N O N H

N

3 Ariakemicin A Type: Oxazoline alkaloids. C32H38N4O7 Reddish-brown amorph. solid. Source: Marine bacterium Rapidithrix sp. HC35. Pharm: Antibacterial (Staphylococcus aureus, MID = 0.46 μg/disk). Ref: N. Oku, et al, Org. Lett., 2008, 10, 2481

https://doi.org/10.1515/9783110653908-001

2

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O

O

O HO

N H

NH

11E

O

O

N H 2N O

4 Ariakemicin B Type: Oxazoline alkaloids. C32H38N4O7 Source: Marine bacterium Rapidithrix sp. HC35. Pharm: Antibacterial (Staphylococcus aureus, MID = 0.46 μg/disk). Ref: N. Oku, et al, Org. Lett., 2008, 10, 2481 O

O

O HO

N H

11Z

NH

O

O

N H2N O

5 Bengazole A O10-Tetradecanoyl-deacylbengazole C Type: Oxazoline alkaloids. C27H44N2O8 Viscous oil, [α]D20 = +5° (c = 0.107, MeOH). Source: Sponges Stelletta splendens (Fiji, 1996), Jaspis sp. (yield = 0.27% dw, Australia) and Jaspidae sp. Pharm: Cytotoxic (interesting and valuable cancer cell growth inhibitor: P388, GI50 = 0.14 μg/mL; OVCAR-3, GI50 = 0.28 μg/mL; NCI-H460, GI50 = 0.21 μg/mL; KM20L2, GI50 = 0.0031 μg/mL; DU145, GI50 = 0.15 μg/mL; BXPC3, GI50 = 0.14 μg/mL; SF295, GI50 = 0.19 μg/mL); anthelminthic; antifungal (Candida albicans, 0.5 μg/disk, IZD = 9–10.5 mm). Ref: M. Adamczeski, et al, JACS, 1988, 110, 1598│P. A. Searle, et al, JOC, 1996, 61, 4073│A. Groweiss, et al, JNP, 1999, 62, 1691│G. R. Pettit, et al, JNP, 2008, 71, 438 OH

OH

OH

O N

N

OH

10

O

O O

6 Bengazole B Type: Oxazoline alkaloids. C28H46N2O8 Viscous oil, [α]D20 = +4.7° (c = 0.024, MeOH). Source: Sponges Stelletta splendens (Fiji, 1996), Jaspis sp. (Australia) and Jaspidae

4.1 Oxazoline Alkaloids

3

sp. Pharm: Cytotoxic (interesting and valuable cancer cell growth inhibitor: P388, GI50 = 0.053 μg/mL; OVCAR-3, GI50 = 0.37 μg/mL; NCI-H460, GI50 = 0.20 μg/ mL; KM20L2, GI50 = 0.33 μg/mL; DU145, GI50 = 0.15 μg/mL; BXPC3, GI50 = 0.18 μg/ mL; SF295, GI50 = 0.19 μg/mL); anthelminthic; antifungal (Candida albicans, 0.5 μg/disk, IZD = 9–10.5 mm). Ref: M. Adamczeski, et al, JACS, 1988, 110, 1598│R. Fernández, et al, JNP, 1999, 62. 678│G. R. Pettit, et al, JNP, 2008, 71, 438 OH

OH

OH

O N

N

OH

10

O

O O

7 Bengazole C O10-Tridecanoyl-deacylbengazole C Type: Oxazoline alkaloids. C26H42N2O8 Oil. Source: Sponge Jaspis sp. (Great Barrier Reef). Pharm: Antifungal (Candida albicans, 0.5 μg/disk, IZD = 9–10.5 mm). Ref: P. A. Searle, et al, JOC, 1996, 61, 4073 OH

N O

O

OH

OH

OH

N O

O

8 Bengazole C4 O4-Tetradecanoyl-bengazole Z Type: Oxazoline alkaloids. C27H44N2O7 Colourless oil. Source: Sponges Stelletta sp. (Jamieson Reef, Bonaparte Archipelago, Australia) and Jaspis cf. coriacea (Papua New Guinea). Pharm: Cytotoxic (SF268, GI50 = 0.3 μmol/L; MCF7, GI50 = 0.8 μmol/L; H460, GI50 = 0.1 μmol/L; HT29, GI50 = 0.6 μmol/L; CHO-K1, GI50 = 1.2 μmol/L). Ref: J. Rodríguez, et al, JNP, 1993, 56, 2034│S. P. B. Ovenden, et al, Mar. Drugs, 2011, 9, 2469

4

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O OH

O

OH

N OH

O N O

9 Bengazole C6 O6-Tetradecanoyl-bengazole Z Type: Oxazoline alkaloids. C27H44N2O7 Colourless oil. Source: Sponges Stelletta sp. (Jamieson Reef, Bonaparte Archipelago, Australia) and Jaspis cf. coriacea (Papua New Guinea). Pharm: Cytotoxic (SF268, GI50 = 0.02 μmol/L; MCF7, GI50 = 0.06 μmol/L; H460, GI50 < 0.02 μmol/L; HT29, GI50 = 0.1 μmol/L; CHOK1, GI50 = 0.8 μmol/L). Ref: J. Rodríguez, et al, JNP, 1993, 56, 2034│S. P. B. Ovenden, et al, Mar. Drugs, 2011, 9, 2469 O

O

OH

OH

N O

OH

N O

10 Bengazole D O10-(12-Methyltridecanoyl)-deacylbengazole C Type: Oxazoline alkaloids. C27H44N2O8 Oil. Source: Sponge Jaspis sp. (Great Barrier Reef). Pharm: Antifungal (Candida albicans, 0.5 μg/disk, IZD = 9–10.5 mm). Ref: P. A. Searle, et al, JOC, 1996, 61, 4073 OH

O

OH

OH

OH

N

O N O

O

11 Bengazole E O10-Pentadecanoyl-deacylbengazole C Type: Oxazoline alkaloids. C28H46N2O8 Oil. Source: Sponges Stelletta splendens (Fiji, 1996) and Jaspis sp. (Great Barrier Reef). Pharm: Antifungal (Candida albicans, 0.5 μg/disk, IZD = 9–10.5 mm); cytotoxic

4.1 Oxazoline Alkaloids

5

(interesting and valuable cancer cell growth inhibitor: P388, GI50 = 0.074 μg/mL; OVCAR-3, GI50 = 0.16 μg/mL; NCI-H460, GI50 = 0.14 μg/mL; KM20L2, GI50 = 0.18 μg/mL; DU145, GI50 = 0.11 μg/mL; BXPC3, GI50 = 0.081 μg/mL; SF295, GI50 = 0.13 μg/mL); anthelmintic. Ref: P. A. Searle, et al, JOC, 1996, 61, 4073│G. R. Pettit, et al, JNP, 2008, 71, 438 OH

OH

OH

O OH

N

N 10

O

O O

12 Bengazole F O10-(13-Methylpentadecanoyl)-deacylbengazole C Type: Oxazoline alkaloids. C29H48N2O8 Oil. Source: Sponge Jaspis sp. (Great Barrier Reef). Pharm: Antifungal (Candida albicans, 0.5 μg/disk, IZD = 9–10.5 mm). Ref: P. A. Searle, et al, JOC, 1996, 61, 4073 OH

O

OH

OH

OH

N O

N O

O

13 Bengazole G O10-Hexadecanoyl-deacylbengazole C Type: Oxazoline alkaloids. C29H48N2O8 Oil. Source: Sponge Jaspis sp. (Great Barrier Reef). Pharm: Antifungal (Candida albicans, 0.5 μg/disk, IZD = 9–10.5 mm). Ref: P. A. Searle, et al, JOC, 1996, 61, 4073 OH

O

OH

N

O N O

O

OH

OH

6

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

14 Bengazole Z Type: Oxazoline alkaloids. C13H18N2O6 Colourless oil, [α]D = −7.5° (c = 0.17, MeOH). Source: Sponges Stelletta sp. (Jamieson Reef, Bonaparte Archipelago, Australia) and Jaspis sp. (Australia). Pharm: Cytotoxic (SF268, GI50 = 22 μmol/L; MCF7, GI50 = 18 μmol/L; H460, GI50 = 8 μmol/L; HT29, GI50 = 13 μmol/L; CHO-K1, GI50 = 04 μmol/L). Ref: A. Groweiss, et al, JNP, 1999, 62, 1691│S. P. B. Ovenden, et al, Mar. Drugs, 2011, 9, 2469 OH

OH

OH

N OH

O N O

15 Enigmazole A Type: Oxazoline alkaloids. C29H46NO10P Pale yellow solid, [α]D25 = −2.7° (c = 0.2, MeOH). Source: Sponge Cinachyrella enigmatica (Papua New Guinea). Pharm: Cytotoxic. Ref: N. Oku, et al, JACS, 2010, 132, 10278

O O H OH

13

P

OH

O H

OH

15

O O N O O

16 (–)-Hennoxazole A Type: Oxazoline alkaloids. C29H42N2O6 Light yellow oil, [α]D25 = −47° (c = 3.12, CHCl3), [α]D = −42.7°. Source: Sponge Polyfibrospongia sp. Pharm: Antiviral (HSV-1, IC50 = 0.6 μg/mL); analgesic (peripheral). Ref: T. Ichiba, et al, JACS, 1991. 113, 3173│P. Wipf, et al, JACS, 1995, 117, 558│D. R. Williams, et al, JACS, 1999, 121, 4924

4.1 Oxazoline Alkaloids

7

OH O

O

H N N

O

O

O

17 Hennoxazole B Type: Oxazoline alkaloids. C30H44N2O6 Source: Sponge Polyfibrospongia sp. Pharm: Analgesic. Ref: T. Ichiba, et al, JACS, 1991, 113, 3173

OH O

4

H

2

O

N

O

N

O O

18 JBIR 34 Type: Oxazoline alkaloids. C21H25ClN4O7 Oil, [α]D25 = −140° (c = 0.6, MeOH). Source: Marine-derived streptomycete Streptomyces sp. Sp080513GE-23 from sponge Haliclona sp. (Tateyama City, Chiba, Japan). Pharm: Antioxidant (DPPH scavenger, IC50 = 1.0 mmol/L, weak). Ref: K. Motohashi, et al, JNP, 2010, 73, 226 O

O H N O OH

N

N H

OH O OH

5

Cl

N

19 JBIR 35 Type: Oxazoline alkaloids. C20H23ClN4O7 Oil, [α]D25 = −140° (c = 0.4, MeOH). Source: Marine-derived streptomycete Streptomyces sp. Sp080513GE-23 from sponge Haliclona sp. (Tateyama City, Chiba, Japan). Pharm: Antioxidant (DPPH scavenger, IC50 = 2.5 mmol/L, weak). Ref: K. Motohashi, et al, JNP, 2010, 73, 226

8

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O

O H N

OH

N H

O OH

N

O OH

5

N

Cl

20 Leucascandrolide A Type: Oxazoline alkaloids. C38H56N2O10 [α]D20 = +41° (EtOH). Source: Calcareous sponge Leucascandra caveolata (New Caledonia). Pharm: Antifungal (Candida albicans); cytotoxic (strong). Ref: M. D’Ambrosio, et al, Helv. Chim. Acta, 1996, 79, 51 H

H

O

O

O

O

O

O

H

O H N

O

N O

O

21 Lipoxazolidinone A Type: Oxazoline alkaloids. C19H31NO3 Oil, [α]D = −31° (c = 0.02, MeOH). Source: Marine bacterium Marinispora sp. NPS008920 (marine sediment, Guam). Pharm: Antibacterial (Staphylococcus sp., Streptococcus pneumoniae, Enterococcus faecalis, MIC = 0.5–16 μg/mL). Ref: V. R. Macherla, et al, JNP, 2007, 70, 1454 O

H N

O

O

22 Lipoxazolidinone B Type: Oxazoline alkaloids. C20H33NO3 Oil. Source: Marine bacterium Marinispora sp. NPS008920 (marine sediment, Guam). Pharm: Antibacterial (Staphylococcus sp., Streptococcus pneumoniae, Enterococcus faecalis, MIC = 0.5–16 μg/mL). Ref: V. R. Macherla, et al, JNP, 2007, 70, 1454

4.1 Oxazoline Alkaloids

O

H N

9

O

O

23 Martefragine A Type: Oxazoline alkaloids. C20H25N3O3 Powder, mp 147–148 °C, [α]D26 = −20.3° (c = 0.76, MeOH). Source: Red alga Martensia fragilis. Pharm: Antioxidant (inhibits lipid peroxidization). Ref: S. Takahashi, et al, CPB, 1998, 46, 1527│A. Nishida, et al, Tet. Lett., 1998, 39, 5983 O– O N O N N H

+

H

24 Neopeltolide Type: Oxazoline alkaloids. C31H46N2O9 Oil, [α]D24 = +24° (c = 0.24, MeOH). Source: Two unidentified lithistid sponges (family Neopeltidae, off northwest coast, Jamaica, depth of 442 m and 433 m, using Johnson-Sea-Link submersible). Pharm: Cytotoxic (potent cell proliferation inhibitor: A549, IC50 = 1.2 nmol/L; NCI-ADR-Res, IC50 = 5.1 nmol/L; P388, IC50 = 0.56 nmol/L); antifungal (yeast Candida albicans, MIC = 0.62 μg/mL); cytotoxic (mode of action: picomolar potency against some tumor cell lines while being only cytostatic in others; inhibits oxidative phosphorylation through targeting cytochrome bc1 complex resulting in blocking of mitochondrial ATP synthesis). Ref: A. E. Wright, et al, JNP, 2007, 70, 412│A. E. Wright, Current Opinion in Biotechnology 2010, 21, 801│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev) O O

O O H

H

O

O

O O N

N H

O

10

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

25 Nocardichelin A Type: Oxazoline alkaloids. C40H65N5O8 Solid, [α]D20 = +11.8° (c = 0.19, MeOH). Source: Mangrove-derived actinomycete Nocardia sp. Acta 3026 (from mangrove soil). Pharm: Cytotoxic (AGS, GI50 = 28.2 nmol/L, TGI = 201.7 nmol/L; HepG2, GI50 = 282.4 nmol/L, TGI = 470.7 nmol/L; MCF7, GI50 = 201.7 nmol/L, TGI = 538.0 nmol/L); siderophore (chromazurol S assay, iron-chelating properties were confirmed by positive reaction). Ref: K. Schneider, et al, JNP, 2007, 70, 932 O

O OH

N

H N

N

N H

OH

O

O N

OH

O

26 Nocardichelin B Type: Oxazoline alkaloids. C38H61N5O8 Solid, [α]D20 = +6° (c = 0.3, MeOH). Source: Mangrove-derived actinomycete Nocardia sp. Acta 3026 (from mangrove soil). Pharm: Cytotoxic (AGS, GI50 = 44.7 nmol/L, TGI = 1.5 μmol/L; HepG2, GI50 = 69.9 nmol/L, TGI = 335.4 nmol/L; MCF7, GI50 = 1.13 μmol/L, TGI = 3.49 μmol/L); siderophore (chromazurol S assay, iron-chelating properties were confirmed by positive reaction). Ref: K. Schneider, et al, JNP, 2007, 70, 932 O

O OH

N

H N

N

N H

OH

O

O N

OH

O

27 Synoxazolidinone C Type: Oxazoline alkaloids. C15H15Br2ClN4O3 Source: Ascidian Synoicum pulmonaria (Troms, Norway). Pharm: Antibacterial (modest); antineoplastic (modest). Ref: M. Tadesse, et al, Tet. Lett., 2011, 52, 1804 Cl

Br O

NH

O N Br O

N H

NH2

4.1 Oxazoline Alkaloids

11

28 Caboxamycin Type: Benzoxazoline alkaloids. C14H9NO4 Powder. Source: Marine-derived streptomycete Streptomyces sp. NTK 937 (deepsea). Pharm: Antibacterial (Bacillus subtilis, IC50 = 8 μg/mL). Ref: C. Hohmann, et al, J. Antibiot., 2009, 62, 99 OH

O

HO N O

29 Nakijinamine C Type: Benzoxazoline alkaloids. C26H25BrN5O4S1+ Source: Sponge Suberites sp. (Unten Port, Okinawa). Pharm: Antifungal (Aspergillus niger). Ref: Y. Takahashi, et al, Org. Lett., 2011, 13, 3016│Y. Takahashi, et al, Tetrahedron, 2012, 68, 8545 O

O S

O N

+

O

Br

N

N H

HN N

+

H

30 Nakijinamine E Type: Benzoxazoline alkaloids. C30H28BrN7O22+ Source: Sponge Suberites sp. (Unten Port, Okinawa). Pharm: Antifungal (Aspergillus niger). Ref: Y. Takahashi,et al, Org. Lett., 2011, 13, 3016│Y. Takahashi, et al, Tetrahedron, 2012, 68, 8545 O

N

N

N

+

O Br

N

N H

HN N H

+

12

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

31 Nakijinol B Type: Benzoxazoline alkaloids. C22H29NO3 Source: Sponge Dactylospongia elegans (Pugh Shoal, Northern Territory, Australia). Pharm: Cytotoxic (SF268, GI50 = 24 μmol/L; MCF7, GI50 = 35 μmol/L; H460, GI50 = 24 μmol/L; HT29, GI50 = 21 μmol/L; CHO-K1, GI50 = 11 μmol/L). Ref: S. P. B. Ovenden, et al, JNP, 2011, 74, 65 OH HO

N

H

O

32 7-[(1,2,3,4,4a,7,8,8a-Octahydro-1,2,4a,5-tetramethyl-1-naphthalenyl)methyl]6-benzoxazolol Type: Benzoxazoline alkaloids. C22H29NO2 Oil. Source: Sponge Dysidea sp. (New Zealand). Pharm: Cytotoxic (P388, IC50 = 10 μg/mL); antibacterial (Bacillus subtilis, IC50 = 1 μg/mL); antifungal (Trichophyton mentagrophytes). Ref: M. Stewart, et al, Aust. J. Chem., 1997, 50, 341 N O

H

OH

33 Cycloxazoline Westiellamide Type: Macrocyclic oxazoline alkaloids. C27H42N6O6 Amorph., [α]D = +30° (c = 0.1, MeOH). Source: An unidentified ascidian (Great Barrier Reef), terrestrial cyanobacterium (Westiellopsis prolific, Hawaii). Pharm: Cytotoxic. Ref: T. W. Hambley, et al, Tetrahedron, 1992, 48, 341│M. R. Princep, et al, JNP, 1992, 55, 140

4.1 Oxazoline Alkaloids

13

O

H O N H

O

N

N NH

H

HN

O

N

O

O

34 Diazonamide A Type: Macrocyclic oxazoline alkaloids. C40H34Cl2N6O6 Glass, [α]D = −217.3° (c = 8.8, MeOH). Source: Ascidian Diazona chinensis (Philippines). Pharm: Cytotoxic (A549, GI50 = 0.029 μmol/L; HT29, GI50 = 0.007 μmol/L; MDA-MB-231, GI50 = 0.006 μmol/L); cytotoxic (potent). Ref: N. Lindquist, et al, JACS, 1991, 113, 2303│J. Li, et al, Angew. Chem., Int. Ed., 2001, 40, 4770│R. Fernández, et al, Tet. Lett., 2008, 49, 2283

O

N

HN H N

2

O

N

O

HO

Cl

O Cl 14

NH O

N H H

35 Diazonamide C Type: Macrocyclic oxazoline alkaloids. C40H35Cl2N7O5 Pale yellow solid, [α]D25 = −24.1° (c = 0.1, MeOH). Source: Ascidian Diazona sp. Pharm: Cytotoxic (A549, GI50 = 2.2 μmol/L; HT29, GI50 = 1.8 μmol/L; MDA-MB-231, GI50 = 2.2 μmol/L). Ref: R. Fernández, et al, Tet. Lett., 2008, 49, 2283

14

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

N

HN

O

H N

N

O

2

Cl

O

H 2N

O Cl 14

NH N H H

O

36 Diazonamide D Type: Macrocyclic oxazoline alkaloids. C36H27Cl3N6O4 Pale yellow solid, [α]D25 = −33.5° (c = 0.1, MeOH). Source: Ascidian Diazona sp. Pharm: Cytotoxic (A549, GI50 = 2.9 μmol/L; HT29, GI50 = 2.9 μmol/L; MDA-MB-231, GI50 = 3.1 μmol/L). Ref: R. Fernández, et al, Tet. Lett., 2008, 49, 2283

N

HN H 2N

N

O

2

Cl

O Cl O Cl 14

NH N H

O H

37 Diazonamide E Type: Macrocyclic oxazoline alkaloids. C36H28Cl2N6O4 Pale yellow solid, [α]D25 = −56.8° (c = 0.02, MeOH). Source: Ascidian Diazona sp. Pharm: Cytotoxic (A549, GI50 = 8.0 μmol/L; HT29, GI50 = 5.2 μmol/L; MDA-MB-231, GI50 = 9.0 μmol/L). Ref: R. Fernández, et al, Tet. Lett., 2008, 49, 2283

N

HN H 2N

N

O

2

Cl

O O Cl 14

NH O

N H H

4.1 Oxazoline Alkaloids

15

38 Dihydrohalichondramide Type: Macrocyclic oxazoline alkaloids. C44H62N4O12 Glass, [α]D = −69.7° (c = 1.68, MeOH). Source: Sponges Jaspis sp. (yield = 0.00037% ww, off Ishigaki I., Okinawa), Halichondria sp. and Hexabranchus sanguineus. Pharm: Cytotoxic (sea urchin egg assay, IC99 = 0.5 μg/mL); cytotoxic (L1210, IC50 = 0.03 μg/mL). Ref: M. R. Kernan, et al, JOC, 1988, 53, 5014│S. Matsunaga, et al, JOC, 1989, 54, 1360│J. Kobayashi, et al, JNP, 1993, 56, 787

O H N 33

O O O O O O OH

N

N

O

N O

O O

39 Halichondramide Type: Macrocyclic oxazoline alkaloids. C44H60N4O12 mp 66–68 °C, [α]D = −100.7° (c = 0.42, MeOH). Source: Sponges Jaspis sp. (yield = 0.054% ww, off Ishigaki I., Okinawa), Halichondria sp., Haliclona sp. and Polycitorella sp. Pharm: Antifungal; insecticide; toxic (sea urchins). Ref: M. R. Kernan, et al, JOC, 1988, 53, 5014│J. Kobayashi, et al, JNP, 1993, 56, 787

16

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O H N 33

O O O O O O OH

N

O

N N O

O O

40 Halishigamide A Type: Macrocyclic oxazoline alkaloids. C44H63N5O12 Amorph. solid, [α]D25 = +38° (c = 0.51, MeOH). Source: Sponge Halichondria sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 0.0036 μg/mL, KB, IC50 = 0.012 μg/mL). Ref: J. Kobayashi, et al JNP, 1997, 60, 150 O

N 33

O

O

O

22

O O O OH

5S

N

NH2

N N

O

O O

O

4.1 Oxazoline Alkaloids

17

41 Halishigamide B Type: Macrocyclic oxazoline alkaloids. C43H60N4O13 Amorph. solid, [α]D25 = −72° (c = 0.06, MeOH). Source: Sponge Halichondria sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 4.4 μg/mL, KB, IC50 = 7.5 μg/mL). Ref: J. Kobayashi, et al JNP, 1997, 60, 150

O H N

O O

O O O O N

OH

N

O

H N O

O O

O

42 Halishigamide C Type: Macrocyclic oxazoline alkaloids. C44H64N4O14 Amorph. solid, [α]D27 = −70° (c = 0.12, CHCl3). Source: Sponge Halichondria sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 5.2 μg/mL, KB, IC50 = 6.5 μg/mL). Ref: J. Kobayashi, et al JNP, 1997, 60, 150

18

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O H N

O O

O O O O OH

N

N

O

O O O

O NH2

O

43 Halishigamide D Type: Macrocyclic oxazoline alkaloids. C44H64N4O14 Amorph. solid, [α]D25 = −88° (c = 0.03, MeOH). Source: Sponge Halichondria sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 1.1 μg/mL, KB, IC50 = 1.8 μg/mL). Ref: J. Kobayashi, et al JNP, 1997, 60, 150 N

O O

O O

O O

OH

O

N NH2

O O

O

N O

O

O

4.1 Oxazoline Alkaloids

19

44 32-Hydroxymycalolide A Type: Macrocyclic oxazoline alkaloids. C45H62N4O13 [α]D27 = −90.0° (c = 0.10, MeOH). Source: Sponge Mycale magellanica (Japan waters). Pharm: Cytotoxic (L1210, IC50 = 0.013 μg/mL). Ref: S. Matsunaga, et al, JNP, 1998, 61, 1164

O H

N 32 30

HO O

O O O O O OH

N

N

O

N O

O O

45 30-Hydroxymycalolide A Type: Macrocyclic oxazoline alkaloids. C47H66N4O14 [α]D27 = −86.9° (c = 0.10, MeOH). Source: Sponge Mycale magellanica (Japan waters). Pharm: Cytotoxic (L1210, IC50 = 0.019 μg/mL). Ref: S. Matsunaga, et al, JNP, 1998, 61, 1164

20

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O H N 32

O

30

O HO

O

O O O O N

OH

N

O

N O

O O

46 38-Hydroxymycalolide B Type: Macrocyclic oxazoline alkaloids. C51H72N4O17 [α]D27 = −80.9° (c = 0.10, MeOH). Source: Sponge Mycale magellanica (Japan waters). Pharm: Cytotoxic (L1210, IC50 = 0.015 μg/mL). Ref: S. Matsunaga, et al, JNP, 1998, 61, 1164 O H

N

O O O O

HO

O O

O O O O N

OH

N N O

O O

O

4.1 Oxazoline Alkaloids

21

47 Isohalichondramide Type: Macrocyclic oxazoline alkaloids. C44H60N4O12 Source: Sponges Jaspis sp. (yield = 0.003% ww, off Ishigaki I., Okinawa) and Halichondria sp. Pharm: Ichthyotoxin; antifeedant; spongicide. Ref: M. R. Kernan, et al, JOC, 1988, 53, 5014│J. Kobayashi, et al, JNP, 1993, 56, 787

O H N 33

O O

O O O O OH

N

N

O

N O O O

48 Jaspisamide A 5S-Hydroxy-5,6-dihydrohalichondramide Type: Macrocyclic oxazoline alkaloids. C44H62N4O13 Solid, [α]D17 = −51° (c = 0.13, MeOH). Source: Sponge Jaspis sp. (yield = 0.00054% ww, off Ishigaki I., Okinawa). Pharm: Cytotoxic (L1210, IC50 < 0.001 μg/mL; KB, IC50 = 0.015 μg/mL). Ref: J. Kobayashi, et al, JNP, 1993, 56, 787

22

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

H

O N 33

O O

O

22

O O O OH

N

OH

5S

N 7

O

N O O

O

49 Jaspisamide B 22S-Hydroxyhalichondramide Type: Macrocyclic oxazoline alkaloids. C44H60N4O13 Solid, [α]D17 = −112° (c = 0.19, MeOH). Source: Sponge Jaspis sp. (yield = 0.00008% ww, off Ishigaki I., Okinawa). Pharm: Cytotoxic (L1210, IC50 < 0.001 μg/mL; KB, IC50 = 0.006 μg/mL). Ref: J. Kobayashi, et al, JNP, 1993, 56, 787

4.1 Oxazoline Alkaloids

23

H

O N 33

O O

O

22S

O O

OH O

OH

N

5

N

O

7

N O O

O

50 Jaspisamide C 33R-Methylhalichondramide Type: Macrocyclic oxazoline alkaloids. C45H60N4O12 Solid, [α]D19 = −76° (c = 0.37, MeOH). Source: Sponge Jaspis sp. (yield = 0.0002% ww, off Ishigaki I., Okinawa). Pharm: Cytotoxic (L1210, IC50 < 0.001 μg/mL; KB, IC50 = 0.013 μg/mL). Ref: J. Kobayashi, et al, JNP, 1993, 56, 787

24

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

H O

N 33R

O O

O

22

O O O OH

N

5

N 7

O

N O O

O

51 Kabiramide A Type: Macrocyclic oxazoline alkaloids. C48H71N5O15 [α]D23 = + 6° (c = 0.1, CHCl3). Source: Nudibranch Hexabranchus sp. (eggs). Pharm: Cytotoxic (L1210, IC50 = 0.03 μg/ mL); cell division inhibitor (fertilised sea urchin eggs, IC99 = 1.0 μg/mL). Ref: S. Matsunaga, et al, JOC, 1989, 54, 1360

O

O

O

O O

O

N

O O 3

O

N

O NH2 OH N

47

O

N O

H

OH

O

52 Kabiramide B Type: Macrocyclic oxazoline alkaloids. C47H69N5O14 [α]D20 = +4° (c = 0.6, CHCl3), [α]D20 = +8° (c = 0.1, CHCl3). Source: Sponges Pachastrissa nux (Chumphon I., Surat Thani Province, Thailand) and Pachastrissa nux, nudibranch Hexabranchus sp. (eggs). Pharm: Antimalarial (MRPF K1, IC50 = 1.67 μmol/L, control Dihydroartemisinin, IC50 = 3.8–4.4 nmol/L); cytotoxic (MCF7, IC50 = 0.45 μmol/L, control Camptothecin,

4.1 Oxazoline Alkaloids

25

IC50 = 1.6 nmol/L; hmn fibroblast, IC50 = 0.95 μmol/L, Camptothecin, IC50 = 459.3 nmol/L); cytotoxic (L1210, IC50 = 0.03 μg/mL); cell division inhibitor (fertilised sea urchin eggs, IC99 = 0.2 μg/mL). Ref: S. Matsunaga, et al, JOC, 1989, 54, 1360│T. Sirirak, et al, JNP, 2011, 74, 1288

O

O

O

O

OH O

N

O O

O

N

O NH2 N

O

N O

OH

H

O

53 Kabiramide C Type: Macrocyclic oxazoline alkaloids. C48H71N5O14 [α]D20 = + 10° (c = 0.6, CHCl3), [α]D20 = + 20° (c = 0.1, CHCl3). Source: Sponges Pachastrissa nux (Chumphon, Surat Thani Province, Thailand) and Pachastrissa nux, nudibranch Hexabranchus sp. (eggs). Pharm: Antimalarial (MRPF K1, IC50 = 4.79 μmol/L, control Dihydroartemisinin, IC50 = 3.8–4.4 nmol/L); cytotoxic (MCF7, IC50 = 0.47 μmol/L, control Camptothecin, IC50 = 1.6 nmol/L; hmn fibroblast, IC50 = 7.59 μmol/L, Camptothecin, IC50 = 459.3 nmol/ L); cytotoxic (L1210, IC50 = 0.01 μg/mL); cell division inhibitor (fertilised sea urchin eggs, IC99 = 0.2 μg/mL); antifungal. Ref: S. Matsunaga, et al, JACS, 1986, 108, 847│S. Matsunaga, et al, JOC, 1989, 54, 1360│T. Sirirak, et al, JNP, 2011, 74, 1288

O O

O

O

O O

N O

O

O

N

O NH2

N

O

N O

H

OH

O

54 Kabiramide C acetate Type: Macrocyclic oxazoline alkaloids. C50H73N5O15 Source: An unidentified sponge (family Neopeltidae, Jamaica, depth of 442 m). Pharm: Cytotoxic (mode of action: kabiramides are potent (level nmol/L) cytotoxic (acts via inhibition of actin

26

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

dynamics)); disrupts actin cytoskeleton. Ref: A. E. Wright, Current Opinion in Biotechnology 2010, 21, 801 O 22

32

H

N

O

31

O

O

O

N

O O

O

O

O

N

O NH2

3

47

O

N O

7

O

O

55 Kabiramide D Type: Macrocyclic oxazoline alkaloids. C47H70N4O13 [α]D20 = −11° (c = 0.2, CHCl3), [α]D20 = −5° (c = 0.1, CHCl3). Source: Sponges Pachastrissa nux (Chumphon, Surat Thani Province, Thailand) and Pachastrissa nux, nudibranch Hexabranchus sp. (eggs). Pharm: Antimalarial (MRPF K1, IC50 = 1.87 μmol/L, control Dihydroartemisinin, IC50 = 3.8–4.4 nmol/L); cytotoxic (MCF7, IC50 = 0.02 μmol/L, control Camptothecin, IC50 = 1.6 nmol/L; hmn fibroblast, IC50 = 0.50 μmol/L, Camptothecin, IC50 = 459.3 nmol/L); cytotoxic (L1210, IC50 = 0.02 μg/mL); cell division inhibitor (fertilised sea urchin eggs, IC99 = 0.2 μg/mL). Ref: S. Matsunaga, et al, JOC, 1989, 54, 1360│T. Sirirak, et al, JNP, 2011, 74, 1288

22

O

O

O

O

O

O O

N N

OH

N

O

O

N O

H

OH

O

56 Kabiramide E Type: Macrocyclic oxazoline alkaloids. C49H72N4O14 [α]D23 = −20° (c = 0.1, CHCl3). Source: Nudibranch Hexabranchus sp. (eggs). Pharm: Cytotoxic (L1210, IC50 = 0.02 μg/mL); cell division inhibitor (fertilised sea urchin eggs, IC99 = 0.2 μg/mL). Ref: S. Matsunaga, et al, JOC, 1989, 54, 1360

4.1 Oxazoline Alkaloids

27

O O

O

O

O O

N O

O

O N

O

N

O

N O

O

OH

H

57 Kabiramide G Type: Macrocyclic oxazoline alkaloids. C47H67N5O13 [α]D20 = +27° (c = 0.3, CHCl3), [α]D20 = +38° (c = 0.4, CHCl3). Source: Sponges Pachastrissa nux (Chumphon, Surat Thani Province, Thailand) and Pachastrissa nux. Pharm: Cytotoxic (MCF7, IC50 = 0.02 μmol/L, control Camptothecin, IC50 = 1.6 nmol/L; hmn fibroblast, IC50 = 2.37 μmol/L, Camptothecin, IC50 = 459.3 nmol/L). Ref: C. Petchprayoon, et al, Heterocycles, 2006, 69, 447│T. Sirirak, et al, JNP, 2011, 74, 1288

O O

O

O

O O

N O

O N

O NH2

N

O

N O

H

OH

O

58 Kabiramide J Type: Macrocyclic oxazoline alkaloids. C46H65N5O13 White amorph. solid, [α]D20 = +6° (c = 0.8, MeOH). Source: Sponge Pachastrissa nux (Chumphon, Surat Thani Province, Thailand). Pharm: Antimalarial (MRPF K1, IC50 = 0.31 μmol/L, control Dihydroartemisinin, IC50 = 3.8–4.4 nmol/L); cytotoxic (MCF7, IC50 = 0.02 μmol/L, control Camptothecin, IC50 = 1.6 nmol/L). Ref: T. Sirirak, et al, JNP, 2011, 74, 1288

28

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O O

O

O

OH O

N O

O N

O NH2

N

O

N O

OH

H

O

59 Kabiramide K Type: Macrocyclic oxazoline alkaloids. C46H66N4O12 White amorph. solid, [α]D20 = +9° (c = 0.3, MeOH). Source: Sponge Pachastrissa nux (Chumphon, Surat Thani Province, Thailand). Pharm: Antimalarial (MRPF K1, IC50 = 0.39 μmol/L, control Dihydroartemisinin, IC50 = 3.8–4.4 nmol/L); cytotoxic (MCF7, IC50 = 0.07 μmol/L, control Camptothecin, IC50 = 1.6 nmol/L). Ref: T. Sirirak, et al, JNP, 2011, 74, 1288

O

O

O

O

O O

N O N

OH

N

O

N O

H

OH

O

60 Kabiramide L Type: Macrocyclic oxazoline alkaloids. C45H64N4O12 Source: Sponge Pachastrissa nux (both Koh Tao, Surat Thani Province and Chumphon National Park, Thailand). Pharm: Antimalarial. Ref: T. Sirirak, et al, Nat. Prod. Res., 2013, 27, 1213

4.1 Oxazoline Alkaloids

29

O O

O

O

N

OH O

O N

OH

N

O

N O

H

OH

O

61 Leiodolide A Leiodelide A Type: Macrocyclic oxazoline alkaloids. C31H45NO9 Pale yellow oil. Source: Lithistid sponge Leiodermatium sp. (depth of 240 m, near Uchelbeluu Reef, Palau, using manned submersible Deep Worker). Pharm: Cytotoxic (HCT116, IC50 = 2.5 μmol/L); cytotoxic (NCI’s 60 cell line panel: HL60, GI50 = 0.26 μmol/L; NCI-H522, GI50 = 0.26 μmol/L; OVCAR-3, GI50 = 0.25 μmol/L). Ref: J. S. Sandler, et al, JOC, 2006, 71, 7245; 8684│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev) O N OH O O HO O O HO OH

62 Leiodolide B Leiodelide B Type: Macrocyclic oxazoline alkaloids. C31H44BrNO9 Pale yellow oil. Source: Lithistid sponge Leiodermatium sp. (depth of 240 m, near Uchelbeluu Reef, Palau, using manned submersible Deep Worker). Pharm: Cytotoxic (HCT116, IC50 = 2.5 μmol/L). Ref: J. S. Sandler, et al, JOC, 2006, 71, 7245; 8684│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

30

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O N OH O H O O

O H

HO

O

Br OH

63 33-Methyldihydrohalichondramide Type: Macrocyclic oxazoline alkaloids. C45H64N4O12 [α]D23 = −53° (c = 0.5, CHCl3). Source: Sponge Halichondria sp. Pharm: Cytotoxic (sea urchin egg assay, IC99 = 0.5 μg/mL); cytotoxic (L1210, IC50 = 0.05 μg/mL). Ref: S. Matsunaga, et al, JOC, 1989, 54, 1360 O 22

32

N

O

31

O

O

N

O

O

O O OH

N

3 47

N O

O

O

64 Mycalolide A Type: Macrocyclic oxazoline alkaloids. C47H64N4O14 Yellowish gum, [α]D = −60.3° (c = 0.5, CHCl3). Source: Sponge Mycale sp. (Japan waters). Pharm: Antifungal (pathogenic fungi); cytotoxic (B16, IC50 = 0.5 ng/mL). Ref: N. Fusetani, et al, Tet. Lett., 1989, 30, 2809│S. Matsunaga, et al, JACS, 1999, 121, 8969

4.1 Oxazoline Alkaloids

O

31

O

O

O O

O

O

O

N

N

O O

H

N

OH

N

O

O

O

65 Mycalolide C Type: Macrocyclic oxazoline alkaloids. C51H72N4O16 Yellowish gum, [α]D = −62.1° (c = 3.7, CHCl3). Source: Stony coral Tubastraea faulkneri. Pharm: Cytotoxic (NCI 60 hmn carcinoma cell lines, LC50 = 2.5 μmol/L). Ref: M. A. Rashid, et al, JNP, 1995, 58, 1120 O O N O

O

O

O

O

O

O

N

O O

O N

OH

N

O

O

O

66 Mycalolide D Type: Macrocyclic oxazoline alkaloids. C50H72N4O17 Gum, [α]D = −19.5° (c = 0.5, CHCl3). Source: Stony coral Tubastraea faulkneri. Pharm: Cytotoxic (NCI 60 hmn carcinoma cell lines, LC50 = 0.6 μmol/L). Ref: M. A. Rashid, et al, JNP, 1995, 58, 1120

32

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O

O N O

O

O

O

O

N

O

O

O

O

O

N

OH O

O

HN O

O

67 Mycalolide E Type: Macrocyclic oxazoline alkaloids. C46H62N4O13 Gum, [α]D = −39.0° (c = 0.1, CHCl3). Source: Stony coral Tubastraea faulkneri. Pharm: Cytotoxic. Ref: M. A. Rashid, et al, JNP, 1995, 58, 1120 O

O N O

O

O

O

O

N

O O

O OH

N

N

O

O

68 Phorboxazole A Type: Macrocyclic oxazoline alkaloids. C53H71BrN2O13 Pale yellow solid, [α]D = +44.8° (c = 1, MeOH). Source: Sponge Phorbas sp. (Western Australia coastline). Pharm: Antifungal (in vitro, Candida albicans, 0.1 μg/disk); cytotoxic (NCI’s 60 tumor cell line panel, mean GI50 = 7.9 × 10−10 mol/L); cytotoxic (inhibits growth of HCT116, GI50 = 0.436 nmol/L, HT29, GI50 = 0.331 nmol/L). Ref: P. A. Searle, et al, JACS, 1995, 117, 8126; 1996, 118, 9422│C.J. Forsyth, et al, JACS, 1998, 120, 5597

4.1 Oxazoline Alkaloids

33

O O

OH

Br 13

N O O HO

O

H

O

O N

HO

O

O

O

69 Phorboxazole B Type: Macrocyclic oxazoline alkaloids. C53H71BrN2O13 Pale yellow solid, [α]D = +44.4° (c = 1, MeOH). Source: Sponge Phorbas sp. (Western Australia coastline). Pharm: Antifungal (in vitro, Candida albicans, 0.1 μg/disk); cytotoxic (NCI’s 60 tumor cell line panel, mean GI50 = 7.9 × 10−10 mol/L). Ref: P. A. Searle, et al, JACS, 1995, 117, 8126│P. A. Searle, et al, JACS, 1996, 118, 9422 O O

OH

Br 13

N O O HO

O

H

O

O HO

N O

O O

70 Thiomycalolide A Type: Macrocyclic oxazoline alkaloids. C57H81N7O20S Source: Sponge Mycale sp. (Japan waters). Pharm: Cytotoxic (P388, IC50 = 18 ng/mL). Ref: S. Matsunaga, et al, JNP, 1998, 61, 663

34

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O H N O O O

O

O HOOC COOH H2N

O

O

O

OH N H

O

O

NH N

S N

O

N O

O

O

71 Thiomycalolide B Type: Macrocyclic oxazoline alkaloids. C62H91N7O23S Brownish powder, [α]D = −3.3° (c = 0.1, MeOH). Source: Sponge Mycale sp. (Japan waters). Pharm: Cytotoxic (P388, IC50 = 18 ng/mL). Ref: S. Matsunaga, et al, JNP, 1998, 61, 663 O H

N O O O O

O O

O

O

HOOC

O

COOH

O OH

O

H2N

O

O

NH

N H

N

S

N N O

O O

O

4.1 Oxazoline Alkaloids

35

72 Ulapualide A Type: Macrocyclic oxazoline alkaloids. C46H64N4O13 Oil, [α]D21 = −43.3° (c = 0.3, MeOH); [α]D25 = −42.9° (c = 0.163, MeOH). Source: Nudibranch Hexabranchus sanguineus (egg masses). Pharm: Cytotoxic (L1210, IC50 = 0.01–0.03 μg/mL, cell proliferation inhibitor); antifungal (Candida albicans); antineoplastic. Ref: J. A. Roesener, et al, JACS, 1986, 108, 846│J. Maddock, et al, J. Comput. Aided Mol. De., 1993, 7, 573│S. K. Chattopadhyay, et al, Tet. Lett., 1998, 39, 6095│S. K. Chattopadhyay, et al, JCS Perkin I, 2000, 2429│J. SAllingham, et al, Org. Lett., 2004, 6, 597 O O O

N

H N

O

N

O O

N O O

OH O

O O O

73 Ulapualide B Type: Macrocyclic oxazoline alkaloids. C51H74N4O16 [α]D25 = −21.7° (c = 0.138, MeOH). Source: Nudibranch Hexabranchus sanguineus (egg masses). Pharm: Cytotoxic (L1210, IC50 = 0.01–0.03 μg/mL, cell proliferation inhibitor); antifungal (Candida albicans). Ref: J. A. Roesener, et al, JACS, 1986, 108, 846│J. SAllingham, et al, Org. Lett., 2004, 6, 597 O

O O N

O

N

H

N

O N

O OH

O

O O

H

O O

O O O

O

74 Aerophobin 1 Type: Spirobenzo-isoxazoline alkaloids. C15H16Br2N4O4 mp 164–167 °C (Ac), [α]D = +187° (c = 2.0, MeOH). Source: Sponges Druinella sp. (Fiji), Verongia aerophoba and Verongula rigida, notapsid Tylodina perverse. Pharm: Cytotoxic (A2780, IC50 = 21.53 μg/mL; K562, IC50 = 24.11 μg/mL). Ref: R. Teeyapant, et al, Z. Naturforsch., C, 1993, 48, 640│J. N. Tabudravu, et al, JNP, 2002, 65, 1798

36

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O Br

Br

HO O H N

N

N

O N H

75 Aerophobin 2 Type: Spirobenzo-isoxazoline alkaloids. C16H19Br2N5O4 [α]D = +139° (c = 1.9, MeOH). Source: Sponges Druinella sp. (Fiji), Verongia aerophoba and Aiolochroia crassa. Pharm: Cytotoxic (A2780, IC50 > 10.0 μg/mL; K562, IC50 = 6.91 μg/mL). Ref: G. Cimino, et al, Tet. Lett., 1983, 24, 3029│J. N. Tabudravu,et al, JNP, 2002, 65, 1798 O Br

Br

HO O

H N

N

HN N

NH2

O

76 Aerothionin Type: Spirobenzo-isoxazoline alkaloids. C24H26Br4N4O8 Plates (Me2CO/C6H6), mp 134–137 °C (dec), [α]D = +252° (Me2CO). Source: Sponges Suberea mollis, Aplysina aerophoba, Aplysina fistularis, Aplysina thiona, Pseudoceratina durissima and Psammaplysilla purpurea, crinoid Himerometra magnipinna. Pharm: Antimigratory activity (wound healing assay, highly metastatic MDA-MB-231 cells, 10 μmol/L, migration ≈ 78%, 30 μmol/L, migration ≈ 72%, control 4-S-Ethylphenylmethylene hydantoin (S-ethyl), 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 cells, 10 μmol/L, invasion ≈ 88%, control 4-S-Ethylphenylmethylene hydantoin (S-ethyl), 50 μmol/L, invasion ≈ 53%, negative control DMSO, invasion = 100%). Ref: E. Fattorusso, et al, Chem. Comm., 1970, 752│K. Moody, et al, JCS Perkin I, 1972, 18│J. A. McMillan, et al, Tet. Lett., 1981, 22, 39│M. R. Kernan, JNP, 1990, 53, 615│H. H. Wassermann, et al, JOC, 1998, 63, 5581│M. M. Silva, et al, Aust. J. Chem., 2010, 63, 886│L. A. Shaala, et al, Mar. Drugs, 2012, 10, 2492

4.1 Oxazoline Alkaloids

37

O

O Br

Br

Br

Br

OH

HO O

O

H N

N

H N

N

2

O

O

77 Aplysina archeri Alkaloid Type: Spirobenzo-isoxazoline alkaloids. C22H20Br4N4O9 Source: Sponge Aplysina archeri (yield = 1.24% dw after extraction, Caribbean Sea). Pharm: Antifungal (Criptococcus neoformans ATCC 90113, MIC = 64 μg/mL). Ref: P. Ciminiello, et al, Tetrahedron, 1996, 52, 9863 O Br

Br

HO

O

O

O H N

N

N

N H

O

O

OH

Br

Br O

78 Aplysinamisine I Type: Spirobenzo-isoxazoline alkaloids. C16H17Br2N5O4 Oil, [α]D26 = +121.9° (c = 0.57, MeOH). Source: Sponge Aplysina cauliformis (Puerto Rico). Pharm: Antibacterial (Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, 50–100 μg/ mL). Ref: A. D. Rodriguez, et al, JNP, 1993, 56, 907

38

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O Br

Br

HO O H N

N O

NH N NH2

79 Aplysinamisine II Type: Spirobenzo-isoxazoline alkaloids. C16H23Br2N5O4 [α]D26 = +47.0° (c = 7.9, MeOH). Source: Sponge Aplysina cauliformis (Puerto Rico). Pharm: Antibacterial (Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, 50–100 μg/ mL); cytotoxic (HCT116, IC50 = 10 μg/mL). Ref: A. D. Rodriguez, et al, JNP, 1993, 56, 907 O Br

Br

NH2

HN HN

HO O H N

N O

80 Aplysinamisine III Type: Spirobenzo-isoxazoline alkaloids. C23H25Br4N3O7 Semisolid, [α]D26 = +69° (c = 6.4, MeOH). Source: Sponge Aplysina cauliformis (Puerto Rico). Pharm: Antibacterial (Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, 50–100 μg/mL); cytotoxic (MCF7, IC50 = 30 μg/mL; CCRF-CEM, IC50 = 6 μg/mL; HCT116, IC50 = 10 μg/mL). Ref: A. D. Rodriguez, et al, JNP, 1993, 56, 907

4.1 Oxazoline Alkaloids

39

O Br

Br

HO O

H N

N O

Br O

O

Br OH

N H

81 Araplysillin 1 Araplysillin I Type: Spirobenzo-isoxazoline alkaloids. C21H23Br4N3O5 Amorph., mp 140–142 °C, [α]D = −70° (c = 0.7, MeOH). Source: Sponges Druinella sp. (Fiji) and Psammaplysilla arabica. Pharm: Cytotoxic (A2780, IC50 = 18.57 μg/mL; K562, IC50 = 27.93 μg/mL); ATPase inhibitor; antimicrobial. Ref: A. Longeon, et al, Experientia, 1990, 46, 548│J. N. Tabudravu, et al, JNP, 2002, 65, 1798 O Br

Br

HO Br

O

H N

N O

O

NH2

Br

82 Araplysillin 2 Araplysillin II Type: Spirobenzo-isoxazoline alkaloids. C36H51Br4N3O6 Amorph., mp 40–42 °C, [α]D = −38° (c = 0.73, MeOH). Source: Sponges Druinella sp. (Fiji) and Psammaplysilla arabica. Pharm: Cytotoxic (A2780, IC50 = 14.79 μg/mL; K562, IC50 = 42.70 μg/mL); ATPase inhibitor; antimicrobial. Ref: A. Longeon, et al, Experientia, 1990, 46, 548│J. N. Tabudravu, et al, JNP, 2002, 65, 1798

O Br

Br

HO Br

O H N

N

O HN

O Br

O

40

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

83 Archerine Type: Spirobenzo-isoxazoline alkaloids. C32H36Br4N10O8 Amorph. brown solid, [α]D25 = +111.4° (c = 0.07, MeOH). Source: Sponge Aplysina archeri (Caribbean Sea). Pharm: Antihistamine (isolated gpg ileum). Ref: P. Ciminiello, et al, EurJOC, 2001, 1, 55 O

O

Br

Br

Br

Br

NH2 HO

OH O

N

H N

N

NH

O

H N

N O

O N N H

NH2

84 Ceratinamide A N-Formylpsammaplysin A Type: Spirobenzo-isoxazoline alkaloids. C22H23Br4N3O7 Solid, [α]D24 = −89.7° (c = 0.146, MeOH). Source: Sponge Pseudoceratina purpurea (Japan waters). Pharm: Antifoulant (inhibits settlement and metamorphosis of barnacle larvae). Ref: S. Tsukamoto, et al, Tetrahedron, 1996, 52, 8181 O

Br

Br O OH

O

H N

N

O

Br O

HN 1'

O Br

85 Ceratinamide B 1′-Deoxypsammaplysin D Type: Spirobenzo-isoxazoline alkaloids. C36H51Br4N3O7 Solid, [α]D24 = −53.5° (c = 0.263, Me2CO). Source: Sponge Pseudoceratina purpurea. Pharm: Antifoulant (inhibits settlement and metamorphosis of barnacle larvae). Ref: S. Tsukamoto, et al, Tetrahedron, 1996, 52, 8181

4.1 Oxazoline Alkaloids

41

O

Br

Br O OH H N

O N

Br O

HN

O

1'

O Br

86 Clavatadine C Type: Spirobenzo-isoxazoline alkaloids. C14H17Br2N5O3 Amorph. solid. Source: Sponge Suberea clavata (Queensland, Australia). Pharm: Serine protease factor Xia Inhibitor (weak). Ref: M. S. Buchanan, et al, JNP, 2009, 72, 973 O Br

Br

O

NH2

H N

N

NH

N H

3

O

87 Clavatadine D Type: Spirobenzo-isoxazoline alkaloids. C15H19Br2N5O3 Amorph. solid. Source: Sponge Suberea clavata (Queensland, Australia). Pharm: Serine protease factor Xia Inhibitor (weak). Ref: M. S. Buchanan, et al, JNP, 2009, 72, 973 O Br

Br

O

NH2

H N

N

4

O

N H

NH

88 Clavatadine E Type: Spirobenzo-isoxazoline alkaloids. C14H18BrN5O3 Amorph. solid. Source: Sponge Suberea clavata (Queensland, Australia). Pharm: Serine protease factor Xia Inhibitor (weak). Ref: M. S. Buchanan, et al, JNP, 2009, 72, 973

42

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O Br

O

NH2

H N

N

3

O

N H

NH

89 Fistularin 3 Type: Spirobenzo-isoxazoline alkaloids. C31H30Br6N4O11 Amorphous solid, [α]D = +104.2° (c = 1.67, MeOH). Source: Sponges Aplysina fistularis, Aplysina archeri, Agelas oroides, Pseudoceratina durissima, Verongula sp., Verongia aerophoba and Verongia cavernicola. Pharm: Antiviral (inhibits growth of feline leukaemia virus, ED50 = 22 μmol/L). Ref: Y. Gopichand, et al, Tet. Lett., 1979, 3921│S. P. Gunasekera, et al, JNP, 1992, 55, 509│M. M. Silva, et al, Aust. J. Chem., 2010, 63, 886 O

O Br

Br

Br

Br

OH

Br

HO

OH

O

H N

N

OH O

O H N

N

17

11

O

O

Br

90 11-epi-Fistularin 3 Type: Spirobenzo-isoxazoline alkaloids. C31H30Br6N4O11 Amorph. solid, [α]D25 = +65.2° (c = 1.04, Me2CO). Source: Sponge Agelas oroides (Great Barrier Reef, Australia). Pharm: Antibacterial; cytotoxic (breast cancer cells). Ref: G. M. König, et al, Heterocycles, 1993, 36, 1351 O

O

Br

Br

Br

Br

OH

Br

HO O

H N

N

OH

O

OH H N

O

N

11

O

Br

O

4.1 Oxazoline Alkaloids

43

91 Homoaerothionin Type: Spirobenzo-isoxazoline alkaloids. C25H28Br4N4O8 Amorph. solid, mp 166–167 °C (di-Ac), [α]D = +191.5° (CHCl3). Source: Sponges Suberea mollis, Aplysina aerophoba, Verongia thiona and Verongia cavernicola. Pharm: Antimigratory activity (wound healing assay, highly metastatic MDA-MB-231 cells, 10 μmol/L, migration ≈ 86%, 30 μmol/L, migration ≈ 76%, control 4-S-Ethylphenylmethylene hydantoin (S-ethyl), 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 cells, 10 μmol/L, invasion ≈ 53%, control 4-SEthylphenylmethylene hydantoin (S-ethyl), 50 μmol/L, invasion ≈ 53%, negative control DMSO, invasion = 100%). Ref: M. R. Kernan, JNP, 1990, 53, 615│L. A. Shaala, et al, Mar. Drugs, 2012, 10, 2492 O Br

O Br

Br

Br

HO

OH O

H N

N

O

H N

N

3

O

O

92 11-Hydroxyaerothionin Type: Spirobenzo-isoxazoline alkaloids. C24H26Br4N4O9 Glass, [α]D = +189° (c = 0.15, MeOH). Source: Sponges Aplysina caissara, Aplysina lacunosa and Pseudoceratina durissima. Pharm: Antituberculosis (Mycobacterium tuberculosis H37Rv, 12.5 μg/mL, InRt = 70%). Ref: M. R. Kernan,; et al, JNP, 1990, 53, 615│A.E.-S. Khalid, et al, Tetrahedron, 2000, 56, 949 O O Br

Br Br

Br

HO OH

O

OH

N

O

H N O

N N H O

93 19-Hydroxyaraplysillin N20-sulfamate Type: Spirobenzo-isoxazoline alkaloids. C21H23Br4N3O9S Amorph. solid, [α]D24 = −69° (c = 0.002, MeOH). Source: Sponge Ianthella flabelliformis (Shelburne Bay,

44

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

Queensland, Australia). Pharm: Pyruvate phosphate dikinase (PPDK) inhibitor (nonselective). Ref: C. A. Motti,et al, JNP, 2009, 72, 290 O OH S O

HN O

OH Br

Br

HO Br

Br

O

H N

N

O

O

94 12R-Hydroxy-11-oxoaerothionin Type: Spirobenzo-isoxazoline alkaloids. C24H24Br4N4O10 [α]D25 = +160.7° (12R-hydroxy) or +152.5° (12S-hydroxy). Source: Sponge Aplysina fistularis f. fulva (Bahamas). Pharm: Antituberculosis (Mycobacterium tuberculosis H37Rv, 12.5 μg/mL, InRt = 60%). Ref: M. R. Kernan,; et al, JNP, 1990, 53, 615│P. Ciminiello, et al, JNP, 1994, 57, 705│A. E.-S. Khalid, et al, Tetrahedron, 2000, 56, 949 O

O Br

Br

Br

Br

HO O

H N

N O

O

OH

O H N

OH

N O

95 19-Hydroxypsammaplysin E Type: Spirobenzo-isoxazoline alkaloids. C27H27Br4N3O9 Source: Sponge Aplysinella strongylata (Tulamben Bay, Bali, Indonesia). Pharm: Antiplasmodial (Plasmodium falciparum). Ref: I. W. Mudianta, et al, JNP, 2012, 75, 2132

4.1 Oxazoline Alkaloids

45

O

O

OH

N H

Br O

Br

O Br Br

O

O

N

HO O

N H

96 N-[4-(Methoxycarbonylamino)-2-oxobutyl]-7,9-dibromo-10-hydroxy-8-methoxy1-oxa-2-azaspiro[4.5]deca-2,6,8-triene-3-carboxylic acid amide Type: Spirobenzo-isoxazoline alkaloids. C16H19N3O7Br2 Source: Sponge Aplysina cauliformis (Bahamas). Pharm: Antiproliferation (Hela, IC50 = 50 μg/mL, mammalian protein synthesis inhibitor; cell proliferation inhibitor (mammalian)). Ref: P. Ciminiello, et al, JNP, 1999, 62, 590 O Br

Br

HO O

O

H N

N O

N H

O

O

97 Oceanapia Quinolone alkaloid Type: Spirobenzo-isoxazoline alkaloids. C24H22Br2N6O8 [α]D20 = −150° (c = 0.19, MeOH). Source: Sponge Oceanapia sp. (Australia). Pharm: Novel mycobacterial enzyme mycothiol S-conjugate amidase inhibitor. Ref: G. M. Nicholas, et al, Org. Lett., 2001, 3, 1543 O Br

Br

NH2 HN

HO O

N

OH

O OH

H N

N

N H

O OH

46

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

98 11-Oxoaerothionin Type: Spirobenzo-isoxazoline alkaloids. C24H24Br4N4O9 Powder, mp 174.6–176.6 °C (dec), [α]D25 = +181.15° (c = 2.17, DMSO). Source: Sponges Aplysina lacunosa (Caribbean Sea) and Verongia cavernicola. Pharm: Cytotoxic (HCT116, pronounced and selective activity). Ref: A. L. Acosta,et al, JNP, 1992, 55, 1007│H. Gao,et al, Tetrahedron 1999, 55, 9717│A.E.-S. Khalid, et al, Tetrahedron, 2000, 56, 949 O

O

Br

Br

Br

Br

HO

OH

O

O

N

O

H N

N N H

O

O

99 Psammaplysin A Type: Spirobenzo-isoxazoline alkaloids. C21H23Br4N3O6 Foam, [α]D22 = −65.2° (c = 0.52, MeOH). Source: Sponges Psammaplysilla purpurea [Syn. Druinellapurpurea] (Red Sea; Fiji) and Aplysinella sp. (Federated States of Micronesia). Pharm: Antibacterial (grampositive bacteria); cytotoxic (HCT116); antifoulant. Ref: M. Rotem, et al, Tetrahedron, 1983, 39, 667│D. M. Roll, et al, JACS, 1985, 107, 2916│T. Ichiba, et al, JOC, 1993, 58, 4149 O

Br

Br Br O OH O

H N

N

O

Br

NH2

O

100 Psammaplysin B Type: Spirobenzo-isoxazoline alkaloids. C21H23Br4N3O7 Foam, [α]D25 = −60.2° (c = 0.632, MeOH). Source: Sponge Psammaplysilla purpurea (Red Sea). Pharm: Antibacterial (gram-positive bacteria); antineopalstic (in vivo, hmn colon tumour cells, moderate). Ref: M. Rotem, et al, Tet. Lett., 1983, 39, 667│D. M. Roll, et al, JACS, 1985, 107, 2916│B. R. Copp, et al, JNP, 1992, 55, 822

4.1 Oxazoline Alkaloids

47

O

Br

Br Br O OH O

H N

N

O

Br

NH2 OH

O

101 Psammaplysin C Type: Spirobenzo-isoxazoline alkaloids. C22H25Br4N3O7 Glass, [α]D23 = −57.1° (c = 0.014, MeOH). Source: Sponge Druinella purpurea [Syn. Psammaplysilla purpurea]. Pharm: Cytotoxic (HCT116, IC50 = 3 μg/mL). Ref: B. R. Copp, et al, JNP, 1992, 55, 822 O

Br

Br O OH

O

H N

N

Br O NH

O

2'

1'

Br OH

102 Psammaplysin D Type: Spirobenzo-isoxazoline alkaloids. C36H51Br4N3O8 Oil, [α]D18 = −71.4° (c = 2.8, Me2CO). Source: Sponge Aplysinella sp. (Federated States of Micronesia). Pharm: Anti-HIV (Haitian RF strain of HIV-I, 0.1 μg/mL, InRt = 51%); immunosuppressant. Ref: T. Ichiba, et al, JOC, 1993, 58, 4149

O

Br

Br O OH H N

O N

Br O

HN 1'

O Br

OH

O

48

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

103 Psammaplysin E Type: Spirobenzo-isoxazoline alkaloids. C27H25Br4N3O8 Bright yellow oil, [α]D18 = −80.3° (c = 2.8, Me2CO). Source: Sponges Aplysinella sp. (Federated States of Micronesia) and Pseudoceratina purpurea. Pharm: Cytotoxic (KB and LoVo, 5 μg/mL); modest immunosuppressant (mixed lymphocyte reaction assay, IC50 = 8.32 × 10−1 μg/ mL); antifoulant. Ref: T. Ichiba, et al, JOC, 1993, 58, 4149 O

Br

Br O OH H N

O N

Br

O

O

O

O HN

Br

104 Psammaplysin H Type: Spirobenzo-isoxazoline alkaloids. C24H30Br4N3O61+ Source: Sponge Pseudoceratina sp. (Holmes Reef, Coral Sea, Australia). Pharm: Antimalarial (CRPF). Ref: M. Xu, et al, BoMCL, 2011, 21, 846 O

Br

O

Br N H N

O Br

HO

O

O

Br

N

+

105 Purealidin B Type: Spirobenzo-isoxazoline alkaloids. C24H30Br4N3O51+ Amorph. solid, [α]D18 = −4.5° (c = 1.3, MeOH). Source: Sponges Psammaplysilla purea and Pseudoceratina verrucosa. Pharm: Antibacterial (Staphylococcus aureus, Sarcina lutea). Ref: J. Kobayashi, et al, Tetrahedron, 1991, 47, 6617 O Br

Br

HO Br

O

H N

N

O N

+

O Br

14

19

20

4.1 Oxazoline Alkaloids

49

106 Purealidin J Type: Spirobenzo-isoxazoline alkaloids. C15H17Br2N5O4 Oil (trifluoroacetate), [α]D21 = +24° (c = 0.98, MeOH) (trifluoroacetate). Source: Sponges Psammaplysilla purea (Okinawa) and Druinella sp. (Fiji). Pharm: Epidermal growth factor (EGF) receptor kinase inhibitor (IC50 = 23 μg/mL); cytotoxic (L1210, IC50 > 10 μg/mL; KB, IC50 > 10 μg/mL); cytotoxic (A2780, IC50 > 10.0 μg/mL; K562, IC50 > 10.0 μg/mL). Ref: J. Kobayashi, et al, CPB, 1995, 43, 403│A. Benharref, et al, JNP, 1996, 59, 177│J. N. Tabudravu,et al, JNP, 2002, 65, 1798 O Br

Br

HO O

H N

N

N NH2

O

N H

107 Purealidin K Type: Spirobenzo-isoxazoline alkaloids. C15H17Br2N5O5 Oil (trifluoroacetate), [α]D24 = +26° (c = 0.38, MeOH) (trifluoroaceta). Source: Sponge Psammaplysilla purea (Okinawa). Pharm: Epidermal growth factor (EGF) receptor kinase inhibitor (IC50 = 14 μg/mL); cytotoxic (L1210, IC50 > 10 μg/mL; KB, IC50 > 10 μg/mL). Ref: J. Kobayashi, et al, CPB, 1995, 43, 403 O Br

Br

HO O

H N

N

N NH2

O O

N H

108 Purealidin L Type: Spirobenzo-isoxazoline alkaloids. C15H21Br2N5O4 Oil (trifluoroacetate), [α]D24 = +27° (c = 0.18, MeOH) (trifluoroacetate). Source: Sponges Psammaplysilla purea (Okinawa) and Aiolochroia crassa. Pharm: Cytotoxic (L1210, IC50 > 10 μg/mL; KB, IC50 > 10 μg/mL). Ref: J. Kobayashi, et al, CPB, 1995, 43, 403

50

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

O Br

Br

HO O

NH

H N

N

NH2

N H

O

109 Purealidin P Type: Spirobenzo-isoxazoline alkaloids. C23H27Br4N3O5 Oil (trifluoroacetate), [α]D19 = +6.6° (c = 0.75, MeOH). Source: Sponge Psammaplysilla purea (Okinawa). Pharm: Epidermal growth factor (EGF) receptor kinase inhibitor (IC50 = 18 μg/mL); cytotoxic (L1210, IC50 = 2.9 μg/mL, KB, IC50 = 7.6 μg/mL). Ref: J. Kobayashi, et al, CPB, 1995, 43, 403 O Br

Br

HO Br

O

H N

N O

O

Br

N

110 Purealidin Q Type: Spirobenzo-isoxazoline alkaloids. C23H27Br4N3O5 Oil (trifluoroacetate), [α]D19 = +9.1° (c = 0.39, MeOH). Source: Sponges Psammaplysilla purpurea (depth of 8–10 m, Mandapam, Tamil Nadu, India; Okinawa), Psammaplysilla purea (Okinawa) and Druinella sp. (Fiji). Pharm: Epidermal growth factor (EGF) receptor kinase inhibitor (IC50 = 11 μg/mL); cytotoxic (L1210, IC50 = 0.95 μg/mL; KB, IC50 = 1.2 μg/mL); cytotoxic (A2780, IC50 = 2.54 μg/mL; K562, IC50 = 1.49 μg/mL). Ref: J. Kobayashi, et al, CPB, 1995, 43, 403│J. N. Tabudravu, et al, JNP, 2002, 65, 1798│S. Tilvi, et al, Tetrahedron, 2004, 60, 10207

4.1 Oxazoline Alkaloids

51

O Br

Br

OH O

H N

N

Br

O

O

N

Br

111 Purealidin R Type: Spirobenzo-isoxazoline alkaloids. C10H10Br2N2O4 Oil, [α]D24 = +86° (c = 0.19, MeOH). Source: Sponges Psammaplysilla purea (Okinawa) and Verongula sp. (Caribbean Sea). Pharm: Cytotoxic (L1210, IC50 > 10 μg/mL; KB, IC50 > 10 μg/mL). Ref: J. Kobayashi, et al, CPB, 1995, 43, 403 O Br

Br

HO O N

NH2 O

112 Purealidin S Type: Spirobenzo-isoxazoline alkaloids. C22H25Br4N3O5 Oil. Source: Sponge Druinella sp. (Fiji). Pharm: Cytotoxic (A2780, IC50 = 7.44 μg/mL; K562, IC50 = 6.02 μg/mL). Ref: J. N. Tabudravu, et al, JNP, 2002, 65, 1798 O Br

Br

OH O

H N

N

Br

O

O Br

NH

52

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

113 Subereamolline A Type: Spirobenzo-isoxazoline alkaloids. C17H23Br2N3O6 Amorph. powder, [α]D = +156.5° (c = 0.55, MeOH). Source: Sponge Suberea mollis. Pharm: Antimigratory activity (wound healing assay, highly metastatic MDA-MB-231 cells, 0.3125 μmol/L, migration ≈ 52%, 0.625 μmol/L, migration ≈ 51%, 1.25 μmol/L, migration ≈ 28%, 2.5 μmol/L, migration ≈ 20%, 5 μmol/L, migration ≈ 17%, 10 μmol/L, migration ≈ 6%, control 4-SEthylphenylmethylene hydantoin (S-ethyl), 30 μmol/L, migration ≈ 34%, negative control DMSO, migration ≈ 100%; IC50 = 400 nmol/L); anti-invasive activity (Cultrex BME (basement membrane extract) cell invasion assay, highly metastatic MDA-MB-231 cells, 2 μmol/L, invasion ≈ 38%, control 4-S-Ethylphenylmethylene hydantoin (S-ethyl), 50 μmol/L, invasion ≈ 53%, negative control DMSO, invasion = 100%); antineoplastic (inhibits migration and invasion of hmn breast cancer cells at nanomolar doses, possible scaffold for future design of breast cancer migration and invasion inhibitor). Ref: M. I. Abou-Shoer, et al, JNP, 2008, 71, 1464│L. A. Shaala, et al, Mar. Drugs, 2012, 10, 2492 O Br

Br

HO O

O

H N

N

N H

O

O

4.2 Thiazole and Thiadiazole Alkaloids 114 Agrochelin Type: Thiazole alkaloids. C23H34N2O4S2 Pale yellow oil, [α]D = −20.5° (c = 0.2, CHCl3). Source: Marine bacterium Agrobacterium sp. Pharm: Cytotoxic (P388, A549, HT29, MEL28, IC50 = 0.05–0.2 μg/mL). Ref: L. M. Canedo, et al, Tet. Lett., 1999, 40, 6841│C. Acebal, et al, J. Antibiot., 1999, 52, 983 H OH

S

S N H N

OH

H HO

O

4.2 Thiazole and Thiadiazole Alkaloids

53

115 Anguibactin Type: Thiazole alkaloids. C15H16N4O4S Source: Marine-derived bacterium Vibrio sp. (seawater, W. African Coast), marine-derived bacterium Vibrio anguillarum 775 (iron-deficient cultures). Pharm: Cytotoxic (P388); siderophore. Ref: L. A. Actis, et al, J. Bacteriol., 1986, 167, 57│M. A. F. Jalal, et al, JACS, 1989, 111, 292│M. Sandy, et al, JNP, 2010, 73, 1038 OH

S

OH

N

N

HO N

N H

O

116 Bacillamide A Microbiaeratinin Type: Thiazole alkaloids. C16H15N3O2S Amorph. powder. Source: Marine bacteria Bacillus sp. SY-1, Thermoactinomyces sp. TA66-2, Bacillus endophyticus SP31 and Microbispora aerata IMBAS-11A. Pharm: Algicide (Cochlodinium polykrikoides). Ref: S.-Y. Jeong, et al, Tet. Lett., 2003, 44, 8005│CRC Press, DNP on DVD, 2012, version 20.2 O N

N H

15

S O

N H

117 Barbamide Type: Thiazole alkaloids. C20H23Cl3N2O2S Pale yellow oil, [α]D26 = −89° (c = 1.9, MeOH). Source: Cyanobacterium Lyngbya majuscula (Caribbean Sea). Pharm: Molluscacidal (snail vector Biomphalaria glabrata, LC100 = 21.6 μmol/L). Ref: J. Orjala, et al, JNP, 1996, 59, 427│A. R. Pereira, et al, JNP, 2010, 73, 217

O N H N

O S

Cl

Cl

Cl

54

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

118 Curacin A Type: Thiazole alkaloids. C23H35NOS [α]D20 = +62.0° (c = 1.1, CHCl3); [α]D = +64.3° (c = 0.32, CHCl3); [α]D = +86° (c = 0.64, CHCl3). Source: Cyanobacterium Lyngbya majuscula (Curacao, Caribbean Sea). Pharm: Anticancer-Cell-Effect (model: tubulin, mechanism: tubulin polymerization inhibition) (Gerwick, 2004); Anticancer-CellEffect (model: bovine β-tubulin, mechanism: tubulin polymerization inhibition) (Mitra, 2004); Anticancer-Cell-Effect (model: A549 cells, mechanism: bad protein levels increase) (Catassi, 2006); Anticancer-Cell-Effect (model: A549 cells, mechanism: caspase-3 protein activation) (Catassi, 2006); antimitotic (IC50 = 7–22 nmol/L); antiproliferative (mammalian cell, IC50 = 6.8ng/mL); herbicidal; toxic (brine shrimp). Ref: W. H. Gerwick, et al, JOC, 1994, 59, 1243│T. Hemscheidt, et al, JOC, 1994, 59, 3467│D. G. Nagle, et al, Tet. Lett., 1995, 36, 1189│J. D. White, et al, JACS, 1995, 117, 5612│J. Orjala, et al, JNP, 1996, 59, 427│J. C. Muir, et al, Tet. Lett., 1998, 39, 2861│A. Mitra, et al, Biochemistry 2004, 43, 13955│P. Wipf, et al, Curr. Pharm. Des., 2004, 10, 1417│A.Catassi, et al, Cell. Mol. Life Sci. 2006, 63, 2377│H. Choi, et al, JNP, 2010, 73, 1411

S 9

7

H

O

N H

H

119 Curacin B Type: Thiazole alkaloids. C23H35NOS [α]D25 = +62° (c = 0.84, CHCl3). Source: Cyanobacterium Lyngbya majuscula (Curacao). Pharm: Antimitotic; inhibits binding of radiolabeled colchicine to purified tubulin; anti-inflammatory; immunosuppressant; antiproliferative; toxic (brine shrimp). Ref: H. D. Yoo, et al, JNP, 1995, 58, 1961│P. Wipf, et al, Curr. Pharm. Des., 2004, 10, 1417 7Z

S 9

O

H

N H

H

120 Curacin C Type: Thiazole alkaloids. C23H35NOS [α]D25 = +56° (c = 0.15, CHCl3). Source: Cyanobacterium Lyngbya majuscula (Curacao). Pharm: Antimitotic (potent); inhibits binding of radiolabeled colchicine to purified tubulin. Ref: H.-D. Yooand, et al, JNP, 1995, 58, 1961│P. Wipf, et al, Curr. Pharm. Des., 2004, 10, 1417

4.2 Thiazole and Thiadiazole Alkaloids

55

O 9Z

H

S N

H

H

121 Curacin D Type: Thiazole alkaloids. C22H33NOS Pale yellow oil, [α]D = +33° (c = 0.14, CHCl3). Source: Cyanobacterium Lyngbya majuscula (St. Croix). Pharm: Antimitotic; antineoplastic (tubulin polymerisation inhibitor); toxic (brine shrimp). Ref: B. Marquez, et al, Phytochemistry, 1998, 49, 2387 H S 9

7

H

O

N

H

H

122 10-Dechlorodysideathiazole Type: Thiazole alkaloids. C13H17Cl5N2OS Oil, [α]D = −57.5° (c = 0.6, CHCl3). Source: Sponge Dysidea herbacea (Pacific I.). Pharm: Antifeedant. Ref: M. D. Unson, et al, JOC, 1993, 58, 6336 Cl Cl

Cl

Cl

H N

9

10

Cl

O N

S

123 10-Dechloro-N-methyldysideathiazole Type: Thiazole alkaloids. C14H19Cl5N2OS Prisms, mp 118–119 °C, [α]D = −98.9° (c = 0.5, CHCl3). Source: Sponge Dysidea herbacea (Pacific I.). Pharm: Antifeedant. Ref: M. D. Unson, et al, JOC, 1993, 58, 6336 Cl

Cl

Cl N

Cl

Cl O N

S

56

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

124 4-O-Demethylbarbamide Type: Thiazole alkaloids. C19H21Cl3N2O2S Source: Cyanobacterium Moorea producens. Pharm: Molluscacidal (marine snail Biomphalaria glabrata, potent). Ref: J. Orjala, et al, JNP, 1996, 59, 427│E. J.Kim, et al, Org. Lett., 2012, 14, 5824

N O

O

Cl

Cl

S

N

Cl

125 Demethylisodysidenin Type: Thiazole alkaloids. C17H22Cl6N2O2S Gum, [α]D20 = +52° (c = 2.6, CHCl3). Source: Sponge Dysidea herbacea, cyanobacterium Oscillatoria spongeliae. Pharm: Antihypertensive. Ref: M. D. Unson, et al, Experientia, 1993, 49, 349 Cl

Cl

Cl

Cl

Cl

H

Cl O

O

NH S N

126 9,10-Didechloro-N-methyldysideathiazole Type: Thiazole alkaloids. C14H20Cl4N2OS Oil, [α]D = −79.9° (c = 3.2, CHCl3). Source: Sponge Dysidea herbacea (Pacific I.). Pharm: Antifeedant. Ref: M. D. Unson, et al, JOC, 1993, 58, 6336 Cl

Cl N

Cl

Cl O N

S

127 Dolabellin Type: Thiazole alkaloids. C24H32Cl2N2O8S2 Oil, [α]D28 = −7.3° (c = 0.34, CHCl3). Source: Sea hare Dolabella auricularia. Pharm: Cytotoxic (HeLa-S3). Ref: H. Sone, et al, JOC, 1995, 60, 4774

4.2 Thiazole and Thiadiazole Alkaloids

Cl

O

Cl

O

O

57

OH N

N

OH

O

O

O

S

S

128 Dolastatin 18 Type: Thiazole alkaloids. C35H46N4O4S Powder, [α]D = −2.3° (c = 0.1, MeOH). Source: Sea hare Dolabella auricularia (Papua New Guinea). Pharm: Cytotoxic. Ref: G. R. Pettit, et al, JNP, 1997, 60, 752│G. R. Pettit, et al, BoMCL, 1997, 7, 827

O

H N

O

O

O

H N

N

S

N

129 Dysideathiazole 4,4,4-Trichloro-3-methyl-N-[4,4,4-trichloro-3-methyl-1-(2-thiazolyl)butyl]butanamide Type: Thiazole alkaloids. C13H16Cl6N2OS Needles, mp 176–177 °C, [α]D = −71.8° (c = 2, CHCl3). Source: sponge Dysidea herbacea (Pacific I.). Pharm: Antifeedant. Ref: M. D. Unson, et al, JOC, 1993, 58, 6336 Cl

Cl

Cl

H N

Cl

Cl

Cl O N

S

130 Dysidenin Type: Thiazole alkaloids. C17H23Cl6N3O2S Needles (hexane), mp 98–99 °C, [α]D21 = −98° (c = 0.5, CHCl3). Source: Sponge Dysidea herbacea (Liizard I., Great Barrier Reef). Pharm: Ichthyotoxin; iodine transport inhibitor. Ref: R. Kazlauskas, et al, Tet. Lett., 1977, 3183│J. E. Biskupiak, et al, Tet. Lett., 1984, 25, 2935│N. Dumrongchai, et al, ACGC Chem. Res. Commun., 2001, 13, 17

58

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

Cl 5

Cl N 11

Cl Cl

9

Cl

H O

O Cl H N

S 13

N

131 Hoiamide D Type: Thiazole alkaloids. C35H58N4O7S3 Source: Cyanobacterium Symploca sp. (Kolaio I., Papua New Guinea; Kape Point, Papua New Guinea). Pharm: Carboxylate anion inhibited p53/MDM2 protein binding. Ref: K. L. Malloy, et al, BoMCL, 2012, 22, 683 S S

S

N N

H N

HO

N

O OH OH

O HOOC

132 Isodysidenin Type: Thiazole alkaloids. C17H23Cl6N3O2S Amorphous solid, [α]D22 = +47° (c = 0.88, CHCl3). Source: Sponge Dysidea herbacea (Papua New Guinea). Pharm: Ichthyotoxin; iodine transport inhibitor Ref: C. Charles, et al, Tet. Lett., 1978, 1519│J. E. Biskupiak, et al, Tet. Lett., 1984, 25, 2935 Cl

Cl

Cl

Cl 5

N

Cl

Cl H O

O NH N S

133 Kalkitoxin Type: Thiazole alkaloids. C21H38N2OS Source: Cyanobacterium Lyngbya majuscula. Pharm: Cytotoxic (Trypan blue dye assay, HCT116, IC50 = 0.001 μg/mL) (White, 2004); anticancer-Cell-Effect (model: primary rat cerebellar granule neuron

4.2 Thiazole and Thiadiazole Alkaloids

59

cultures, mechanism: Calcium influx inhibition) (LePage, 2005); ichthyotoxin (common goldfish Carassius auratus, LC50 = 700 nmol/L); toxic (brine shrimp Artemia salina, LC50 = 170 nmol/L); cell division inhibitor (fertilized sea urchin embryo assay, IC50 = 25 nmol/L), neurotoxicity (rat neurons, LC50 = 3.86 nmol/L, inhibitable with NMDA receptor antagonists.3); antiinflammatoty (inflammatory disease model which measured IL-1β-induced PLA2 secretion, HepG2, IC50 = 27 nmol/L); blocker of voltage sensitive Na+channel (neuro-2a, EC50 = 1 nmol/L). Ref: M. Wu, et al, JACS, 2000, 122, 12041│J. D. White, et al, Org. Biomol. Chem. 2004, 2, 2092│F. Yokokawa, et al, Tetrahedron, 2004, 60, 6859│K. T. LePage, et al, Toxicol. Lett. 2005, 158, 133│H. Choi, et al, JNP, 2010, 73, 1411

N N S O

134 Lodopyridone Type: Thiazole alkaloids. C23H21ClN4O4S2 Glass. Source: Marine-derived bacterium Saccharomonospora sp. CNQ-490 (sediment, culture, La Jolla, California). Pharm: Cytotoxic (HCT116, modest). Ref: K. N. Maloney, et al, Org. Lett., 2009, 11, 5422 O O

Cl

S H N

N N

N

OH

S

O

135 N-Methyldysideathiazole Type: Thiazole alkaloids. C14H18Cl6N2OS Needles, mp 96 °C, [α]D = −108.3° (c = 2, CHCl3). Source: sponge Dysidea herbacea (Pacific I.). Pharm: Antifeedant. Ref: M. D. Unson, et al, JOC, 1993, 58, 6336 Cl

Cl

Cl N

Cl

Cl Cl O N

S

136 Mycothiazole Type: Thiazole alkaloids. C22H32N2O3S Viscous oil, [α]D20 = −3.8° (c = 2.9, CHCl3), [α]D27 = −13.7° (c = 0.6, MeOH). Source: Sponge Cacospongia mycofijiensis,

60

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

nudibranch Chromodoris lochi. Pharm: Anthelminthic (in vitro); toxic (highly toxic to mice). Ref: P. Crews, et al, JACS, 1988, 110, 4365│H. Sugiyama, et al, Tetrahedron, 2003, 59, 6579│T. A. Johnson, et al, JMC, 2007, 50, 3795 OH

N

O

S N H

O

137 Pseudodysidenin Type: Thiazole alkaloids. C17H23Cl6N3O2S Cryst., [α]D = −96.9° (c = 0.03, CHCl3). Source: Cyanobacterium Lyngbya majuscula (Caribbean Sea). Pharm: Cytotoxic (A549, HT29 and MEL28). Ref: J. I. Jimenez, et al, JNP, 2001, 64, 200 Cl 5

Cl

H N 11

Cl

9

Cl

H

O

Cl

N

Cl

O S

13

N

138 Pulicatin A Type: Thiazole alkaloids. C11H13NO2S Pale yellow solid (MeOH), [α]D25 = −53° (c = 0.1, CHCl3). Source: Marine-derived streptomycete Streptomyces sp. CP32 from Prosobranch (cone snail) Conus pulicarius (Mactan I., Cebu, Philippines). Pharm: Neuroactive. Ref: Z. Lin, et al, JNP, 2010, 73, 1922 OH 1''

N

OH

5

S

139 Pulicatin B Type: Thiazole alkaloids. C11H13NO2S Pale yellow solid (MeOH), [α]D25 = −25° (c = 0.1, CHCl3). Source: Marine-derived streptomycete Streptomyces sp. CP32 from prosobranch (cone snail) Conus pulicarius (Mactan I., Cebu, Philippines). Pharm: Neuroactive. Ref: Z. Lin, et al, JNP, 2010, 73, 1922

4.2 Thiazole and Thiadiazole Alkaloids

61

OH 1''

OH

N 5

S

140 Pulicatin C 5-Methylaeruginol Type: Thiazole alkaloids. C11H11NO2S Pale yellow solid (MeOH). Source: Marine-derived streptomycete Streptomyces sp. CP32 from prosobranch (cone snail) Conus pulicarius (Mactan I., Cebu, Philippines). Pharm: Neuroactive. Ref: Z. Lin, et al, JNP, 2010, 73, 1922 OH 1''

OH

N 5

S

141 Pulicatin D Type: Thiazole alkaloids. C11H9NO2S Solid (CHCl3). Source: Marine-derived streptomycete Streptomyces sp. CP32 from prosobranch (cone snail) Conus pulicarius (Mactan I., Cebu, Philippines). Pharm: Neuroactive. Ref: Z. Lin, et al, JNP, 2010, 73, 1922 O 1''

OH

N 5

S

142 Pulicatin E Type: Thiazole alkaloids. C11H10N2O2S Pale yellow solid (MeOH). Source: Marinederived streptomycete Streptomyces sp. CP32 from prosobranch (cone snail) Conus pulicarius (Mactan I., Cebu, Philippines). Pharm: Neuroactive. Ref: Z. Lin, et al, JNP, 2010, 73, 1922 O H2N

1''

N 5

S

OH

62

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

143 Watasemycin A Type: Thiazole alkaloids. C16H20N2O3S2 Pale yellow powder, mp 62–65 °C, [α]D28 = +20.5° (c = 0.2, CHCl3). Source: Marine-derived streptomycetes Streptomyces sp. TPA0597 and Streptomyces sp. CP32. Pharm: Antibacterial (gram-positive and -negative bacteria). Ref: T. Sasaki, et al, J. Antibiot., 2002, 55, 249 HO N H H 2

O

OH

N

S S

144 Watasemycin B Type: Thiazole alkaloids. C16H20N2O3S2 Pale yellow powder, mp 58–60 °C, [α]D28 = −2.5° (c = 0.2, CHCl3). Source: Marine-derived streptomycetes Streptomyces sp. TPA0597 and Streptomyces sp. CP32. Pharm: Antibacterial (gram-positive and -negative bacteria). Ref: T. Sasaki, et al, J. Antibiot., 2002, 55, 249 HO N H 2

O

H OH

N

S S

145 Erythrazole B Type: Benzothiazole alkaloids. C33H44N2O7S Light yellowglass. Source: Mangrovederived bacterium Erythrobacter sp. from an unidentified mangrove (sediment, Trinity Bay, Galveston, Texas, USA). Pharm: Cytotoxic (panel of NSCLC cell lines: H1325, IC50 = 1.5 μmol/L; H2122, IC50 = 25 μmol/L; HCC366, IC50 = 6.8 μmol/L). Ref: Y. Hu, et al, Org. Lett., 2011, 13, 6580 OH O 3

OH S N

H N

O OH

O O

4.2 Thiazole and Thiadiazole Alkaloids

63

146 4-Hydroxy-7-[1-hydroxy-2-(methylamino)ethyl]-2(3H)-benzothiazolone Type: Benzothiazole alkaloids. C10H12N2O3S Source: Sponge Dysidea sp. (Okinawa). Pharm: β-Adrenoceptor agonist. Ref: H. Suzuki, et al, BoMCL, 1999, 9, 1361 OH H N O S H N

HO

147 2-Methylbenzothiazole Type: Benzothiazole alkaloids. C8H7NS mp 14 °C, bp 238 °C, bp15 mmHg 150–151 °C, pKa 2.06 (H2O), pKa 8.63 (MeCN). Source: Marine bacterium Micrococcus sp. from sponge Tedania ignis. Pharm: LD50 (mus, ipr) = 300 mg/kg. Ref: A. A. Stierle, et al, Tet. Lett., 1991, 32, 4847 N S

148 Latrunculin A Type: Latrunculins. C22H31NO5S Oil, [α]D24 = +152° (c = 1.2, CHCl3). Source: Sponges Latrunculia magnifica (Red Sea), Latrunculia corticata (Red Sea), Spongia mycofijiensis (Pacific Ocean) and Hyattella sp. (Pacific Ocean), nudibranches Chromodoris hamiltoni, Chromodoris lochi and Chromodoris elisabethina. Pharm: G-actin polymerization inhibitor (blocking polymerization by plugging ATP site of G-actin); ichthyotoxin; PKC inhibitor; cytochalasin-like activity; antiglaucoma; toxin. Ref: Y. Kashman, et al, Tet. Lett., 1980, 21, 3629│I. Spector,et al, Science, 1983, 219, 493 (rev)│R. K. Okuda, et al, Experientia, 1985, 41, 1355│CRC Press, DNP on DVD, 2012, version 20.2

7

6

O 1

O OH O H HN S O

64

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

149 Latrunculin B Type: Latrunculins. C20H29NO5S [α]D24 = +112° (c = 0.48, CHCl3). Source: Sponges Latrunculia magnifica (Red Sea), Latrunculia corticata and Spongia sp., nudibranches Glossodoris quadricolor and Chromodoris hamiltoni. Pharm: G-actin polymerization inhibitor (blocking polymerization by plugging ATP site of G-actin); ichthyotoxic (strongly); insecticide. Ref: I. Spector,et al, Science, 1983, 219, 493 (rev)│D. J. Mebs, Chem. Ecol., 1985, 11, 713

O O OH O

HN

16

S O

150 Latrunculin C Type: Latrunculins. C20H31NO5S Oil. Source: Sponge Latrunculia magnifica (Red Sea). Pharm: Ichthyotoxin. Ref: Y. Kashman, et al, Tetrahedron, 1985, 41, 1905-

O 11

O

OH

OH 15

H

HN S O

151 Latrunculin D Type: Latrunculins. C21H31NO5S Oil. Source: Sponge Latrunculia magnifica. Pharm: Ichthyotoxin. Ref: Y. Kashman, et al, Tetrahedron, 1985, 41, 1905

4.2 Thiazole and Thiadiazole Alkaloids

65

O O O

O H N

H

O

S

152 Latrunculin S Type: Latrunculins. C22H33NO5S [α]D26 = +110° (c = 0.19, CHCl3). Source: Sponge Fasciospongia rimosa (Okinawa). Pharm: Cytotoxic (P388, A549, HT29, MEL28, IC50 = 0.5–1.2 μg/mL). Ref: J. Tanaka, et al, Chem. Lett., 1996, 255

O O OH OH

H HN S O

153 Alotamide A Type: Macrocyclic thiazole alkaloids. C32H49N3O5S [α]D25 = −1.9° (c = 0.16, CH2Cl2). Source: Cyanobacterium Lyngbya bouillonii. Pharm: Anticancer-Cell-Effect (model: murine cerebrocortical neurons, mechanism: calcium influx promotion); neuropharmacological agent. Ref: I. E. Soria-Mercado, et al, Org. Lett. 2009, 11, 4704

O

O O

S

H

H

N O

N

N O

66

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

154 Mayotamide A Type: Macrocyclic thiazole alkaloids. C30H43N7O4S4 Amorph. powder, [α]D = +77° (c = 0.17, MeOH). Source: Ascidian Didemnum molle (Mayotte lagoon, Comoros Is.). Pharm: Cytotoxic (A549, HT29 and MEL28, IC50 = 5–10 μg/mL, mild). Ref: A. Rudi, et al, Tetrahedron, 1998, 54, 13203 O

N

S

O

N H

S

N

NH O

S

N O N NH

S

155 Mayotamide B Type: Macrocyclic thiazole alkaloids. C29H41N7O4S4 Amorph. powder, [α]D = +130° (c = 0.1, MeOH). Source: Ascidian Didemnum molle (Mayotte lagoon, Comoros Is.). Pharm: Cytotoxic (A549, HT29 and MEL28, IC50 = 5–10 μg/mL, mild). Ref: A. Rudi, et al, Tetrahedron, 1998, 54, 13203 O

N

S

O

N H

S

N

NH O

N

S

O N S

NH

156 (–)-Pateamine A Type: Macrocyclic thiazole alkaloids. C31H43N3O4S [α]D = −253° (MeOH). Source: Sponge Mycale sp. (New Zealand). Pharm: Cytotoxic (P388, IC50 = 0.15 ng/mL);

4.2 Thiazole and Thiadiazole Alkaloids

67

immunosuppressant. Ref: P. T. Northcote, et al, Tet. Lett., 1991, 32, 6411│R. M. Rzasa, et al, JACS, 1998, 120, 591│D. Romo, et al, JACS, 1998, 120, 12237

S

N N

O O

H 2N O

O

157 Patellazole A Type: Macrocyclic thiazole alkaloids. C49H77NO11S Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (NCI hmn cell line protocol, mean IC50 = 10−3–10-6 μg/mL); antifungal (Candida albicans); cytotoxic (KB, IC50 = 10 ng/mL); selective cytotoxicity (Corbett assay, zone differential < 250 zone units, no selective cytotoxicity). Ref: Zabriskie, T. M. et al, JACS, 1988, 110, 7919; 7920│D. E. Williams, et al, JNP, 1989, 52, 732 OH

O

OH OH 41

OH

O N

O

O 36

S

O O

O

158 Patellazole B Patellide Type: Macrocyclic thiazole alkaloids. C49H77NO12S Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (NCI hmn cell line protocol, mean IC50 = 10−3– 10−6 μg/mL); antifungal (Candida albicans); cytotoxic (KB, IC50 = 0.3 ng/mL); selective cytotoxicity (Corbett assay, zone differential < 250 zone units, no selective cytotoxicity). Ref: Zabriskie, T.M. et al, JACS, 1988, 110, 7919; 7920│D. E. Williams, et al, JNP, 1989, 52, 732

68

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

OH

O

OH OH 41

OH

O N

O

S

O

O

O

O

HO 36

159 Patellazole C Type: Macrocyclic thiazole alkaloids. C49H77NO13S [α]D = −100° (c = 1.06, CH2Cl2). Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (NCI hmn cell line protocol, mean IC50 = 10−3–10−6 μg/mL); antifungal (Candida albicans). Ref: T. M. Zabriskie, et al, JACS, 1988, 110, 7919; 7920 OH

O

OH OH OH 41

OH

O N

O HO

S

O

O O

36

O

160 Dendrodoine Type: Thiadiazole alkaloids. C13H12N4OS Crystal (EtOAc), mp 280–285 °C. Source: Ascidian Dendrodoa grossularia. Pharm: Cytotoxic. Ref: S. Heitz, et al, Tet. Lett., 1980, 21, 1457│I. T. Hogan, et al, Tetrahedron, 1984, 40, 681 O N N H

S

N N

4.3 Oxazoline-Thiazole Macrocyclic Alkaloids

69

161 Polycarpathiamine A Type: Thiadiazole alkaloids. C9H7N3O2S Source: Ascidian Polycarpa aurata (Ambon, Indonesia). Pharm: Cytotoxic (L5178Y, submicromolar). Ref: C. -D. Pham, et al, Org. Lett., 2013, 15, 2230 O N NH2 S

HO

N

4.3 Oxazoline-Thiazole Macrocyclic Alkaloids 162 Dolastatin E Type: Oxazoline-thiazole macrocyclic alkaloids. C21H26N6O4S2 Powder, [α]D27 = −22° (c = 0.22, MeOH). Source: Sea hare Dolabella auricularia. Pharm: Cytotoxic (HeLa-S3, IC50 = 22–40 μg/mL). Ref: M. Ojika, et al, Tet. Lett., 1995, 36, 5057│M. Nakamura, et al, Tet. Lett., 1995, 36, 5059 O S

N H N

O

N

HN

NH O

O

N S

163 Lissoclinamide 1 Type: Oxazoline-thiazole macrocyclic alkaloids. C35H43N7O5S2 Source: An unidentified ascidian. Pharm: Cytotoxic (L1210, IC50 = 10 μg/mL, borderline). Ref: J. E. Biskupiak, et al, JOC, 1983, 48, 2304│J. M. Wasylyk, et al, JOC, 1983, 48, 4445

70

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

S N

O

O

N H

O HN

N N S

H N

N

O O

164 Lissoclinamide 4 Type: Oxazoline-thiazole macrocyclic alkaloids. C38H43N7O5S2 Powder (Et2O), mp 152–154 °C, [α]D = +45° (c = 0.7, CHCl3). Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (T24, 1 μg/mL, incorporation of [methyl-3H] thymidine, percentage of incorporation of untreated cells = 40%). Ref: F. J. Schmitz, et al, JOC, 1989, 54, 3463│B. M. Degnan, et al, JMC, 1989, 32, 1349│C. D. J. Boden, et al, JCS Perkin I, 2000, 875 O S

N H

O N

N

N O

O

HN H N

O

N S

165 Lissoclinamide 5 Type: Oxazoline-thiazole macrocyclic alkaloids. C38H41N7O5S2 Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (T24, 50 μg/mL, incorporation of [methyl-3H] thymidine, percentage of incorporation of untreated cells = 65%, less activity than Lissoclinamide 4 by two orders of magnitude). Ref: F. J. Schmitz, et al, JOC, 1989, 54, 3463│B. M. Degnan, et al, JMC, 1989, 32, 1349│C. Boden, et al, Tet. Lett., 1994, 35, 8271│C. D. J. Boden, et al, JCS Perkin I, 2000, 875

4.3 Oxazoline-Thiazole Macrocyclic Alkaloids

71

O S

N H

O

29

N

N

28

O

O

N

HN H N

N S

O

166 Lissoclinamide 6 Type: Oxazoline-thiazole macrocyclic alkaloids. C38H43N7O5S2 Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic. Ref: B. M. Degnan, et al, JMC, 1989, 32, 1349 O S

N H

O

N

N

O O

N

HN NH N O S

167 Mechercharstatin A Mechercharmycin A Type: Oxazoline-thiazole macrocyclic alkaloids. 25 C35H32N8O7S Powder, [α]D = +110° (c = 0.04, DMSO). Source: Marine-derived bacterium Thermoactinomyces sp. YM3-251. Pharm: Cytotoxic (A549, IC50 = 4.0 × 10−8 mol/L; JurKat, IC50 = 4.6 × 10−8 mol/L). Ref: K. Kanoh, et al, J. Antibiot., 2005, 58, 289 S O O

N N

N

O O

N

N H N O

H N

H

H N O

O

72

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

168 Nagelamide Z Type: Oxazoline-thiazole macrocyclic alkaloids. C22H26Br4N10O22+ Pale yellow amorphous solid, [α]D22 ≈ −3.0° (c = 0.25, MeOH). Source: Sponge Agelas sp. (Kerama I., Okinawa). Pharm: Antibacterial (Escherichia coli, MIC > 32 μg/mL, Staphylococcus aureus, MIC = 16 μg/mL, Bacillus subtilis, MIC > 32 μg/mL, Micrococcus luteus, MIC = 8.0 μg/mL); antifungal (Aspergillus niger, IC50 = 4.0 μg/mL, Trichophyton mentagrophytes, IC50 = 4.0 μg/mL, Candida albicans, IC50 = 0.25 μg/mL, potent, Cryptococcus neoformans, IC50 = 2.0 μg/mL). Ref: N. Tanaka, et al, Org. Lett., 2013, 15, 3262 Br

H N

H +

N

H N

Br

H

N H

N H

O

O HN

H

N

N H

H N Br

N H

+

Br

H

169 Nostocyclamide Type: Oxazoline-thiazole macrocyclic alkaloids. C20H22N6O4S2 Cryst. (EtOAc/petrol), mp 255.8–256.9 °C (dec), [α]D = +25° (CHCl3). Source: Cyanobacterium Nostoc sp. 31 (freshwater). Pharm: Anticyanobacterial; antialgal; toxic (freshwater rotifer Brachionus calyciflorus). Ref: A. K. Todorova, et al, JOC, 1995, 60, 7891 O

S

N H

O

S N

N

HN

NH N

O O

170 Nostocyclamide M Type: Oxazoline-thiazole macrocyclic alkaloids. C20H22N6O4S3 Needles. Source: Cyanobacterium Nostoc sp. 31 (freshwater). Pharm: Allelopathic. Ref: F. Juettner, et al, Phytochemistry, 2001, 57, 613

4.3 Oxazoline-Thiazole Macrocyclic Alkaloids

73

S O

S

O

N H

S

N

N

NH

HN N O O

171 Theonezolide A Type: Oxazoline-thiazole macrocyclic alkaloids. C79H140N4O22S2 Needles +3H2O, mp 123 °C, [α]D28 = −8.1° (c = 1.5, MeOH). Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Cytotoxic (KB and L1210, both IC50 = 0.75 μg/mL). Ref: J. Kobayashi, et al, JACS, 1993, 115, 6661│K. Kondo, et al, Tetrahedron, 1994, 50, 8355│J. Kobayashi, et al, Heterocycles, 1998, 49, 39│M. Sato, et al, Tetrahedron, 1998, 54, 4819│K. Nozawa, et al, Tet. Lett., 2013, 54, 783

O OH

HO

OH

OH

OH O

S

O

O

HO

O O N

HO

NH O

NH2

O OH OH

OH

OH

OH

N O

OH

S

172 Theonezolide B Type: Oxazoline-thiazole macrocyclic alkaloids. C77H136N4O22S2 Colorless solid, mp = 125 °C, [α]D28 = −8.0° (c = 1.5, MeOH). Source: Lithistid sponge Theonella sp.

74

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

(Japan waters). Pharm: Cytotoxic (L1210, IC50 = 11 μg/mL, KB, IC50 = 0.37 μg/mL). Ref: J. Kobayashi, et al, JACS, 1993, 115, 6661│K. Kondo, et al, Tetrahedron, 1994, 50, 8355│J. Kobayashi, et al, Heterocycles, 1998, 49, 39│M. Sato, et al, Tetrahedron, 1998, 54, 4819│K. Nozawa, et al, Tet. Lett., 2013, 54, 783

O OH

HO

OH

OH

OH O

S

O

O HO

O O N

HO

NH O O

NH2

OH OH

OH

OH

OH

N O

OH

S

173 Theonezolide C Type: Oxazoline-thiazole macrocyclic alkaloids. C81H144N4O22S2 Colorless solid, mp 122 °C, [α]D28 = −7.5° (c = 1.5, MeOH). Source: Lithistid sponge Theonella sp. (Japan waters). Pharm: Cytotoxic (L1210, IC50 = 0.37 μg/mL, KB, IC50 = 0.37 μg/ mL). Ref: J. Kobayashi, et al, JACS, 1993, 115, 6661│K. Kondo, et al, Tetrahedron, 1994, 50, 8355│J. Kobayashi, et al, Heterocycles, 1998, 49, 39│M. Sato, et al, Tetrahedron, 1998, 54, 4819│K. Nozawa, et al, Tet. Lett., 2013, 54, 783

4.3 Oxazoline-Thiazole Macrocyclic Alkaloids

75

O OH

OH

OH

HO

OH O

S

O

O

HO

O O

NH2 HO

N

NH O O OH

OH

OH

OH

OH

N O

OH

S

174 Urukthapelstatin A Type: Oxazoline-thiazole macrocyclic alkaloids. C34H30N8O6S2 Powder, mp 311 °C (dec), [α]D22 = + 38° (c = 0.15, CHCl3). Source: Marine-derived actinomycete Mechercharimyces asporophorigenens YM11-542. Pharm: Cytotoxic (A549, IC50 = 12 nmol/L); cytotoxic (panel of hmn cancer cell lines). Ref: Y. Matsuo, et al, J. Antibiot., 2007, 60, 251 S S O

N N

N

O N

N

O

HN

NH

H

H N

O O

O

76

4 Oxazolines Thiazoles Thiadiazoles and Triazoles

4.4 Triazole Alkaloids 175 Essramycin Type: Triazole alkaloids. C14H12N4O2 Amorph. solid, mp 219–221 °C (natural), mp 241–243 °C (synthetic). Source: Marine-derived streptomycete Streptomyces sp. Merv8102, marine-derived actinomycete Nocardia sp. ALAA. Pharm: Antibacterial (natural, active; synthetic, inactive); antibacterial (Bacillus subtilis, Staphylococcus aureus and Micrococcus luteus, MIC = 1–85 μg/mL). Ref: M. M. A. El-Gendy, et al, J. Antibiot., 2008, 61, 149; 379│E. H. L. Tee, et al, JNP, 2010, 73, 1940 O

O N

N

N

N H

176 Penipanoid A Type: Triazole alkaloids. C16H13N3O3 Colorless crystals (MeOH), mp 212–214 °C. Source: Marine-derived fungus Penicillium paneum (sediment, South China Sea). Pharm: Cytotoxic (SMMC-7721, IC50 = 54.2 μmol/L, control Fluorouracil, IC50 = 13.0 μmol/L); antibacterial (Staphylococcus aureus and Escherichia coli); antifungal (Alternaria brassicae, Fusarium oxysporium f. sp. vasinfectum, Coniella diplodiella, Physalospora piricola and Aspergillus niger). Ref: C.-S. Li, et al, JNP, 2011, 74, 1331 O

OH N N

N

OH

5 Pyridines and Piperidines 5.1 Pyridine Alkaloids 177 Agelongine Type: Pyridine alkaloids. C13H11BrN2O4 Amorph. solid. Source: Sponges Agelas conifera (Caribbean, yield = 2.5% dw), Agelas dispar (Caribbean, yield = 2.5% dw), Agelas clathrodes (Caribbean, yield = 2.3% dw), Agelas longissima (Caribbean, yield = 2.2% dw) and Axinella damicornis. Pharm: Antiserotonergic. Ref: F. Cafieri, et al, BoMCL, 1995, 5, 799; 1997, 7, 2283│A. Aiello, et al, Tetrahedron, 2005, 61, 7266 Br O O N H

N

+

–

O

O

178 Antibiotic PF 1140 Type: Pyridine alkaloids. C16H23NO3 Cryst., [α]D = −148° (MeOH). Source: Marinederived fungus Penicillium sp., terrestrial fungus (Eupenicillium sp. PF1140). Pharm: Antifungal. Ref: Y. Fujita, et al, J. Antibiot., 2005, 58, 425 O HO

H

N O

179 Antibiotic ZZF 51 Type: Pyridine alkaloids. C20H24CuN2O4 Blue cryst., mp 253–254 °C. Source: Mangrove-derived fungus Fusarium sp. from mangrove Castanopsis fissa (China waters). Pharm: Antibacterial (against 4 bacterial strains); cytotoxic (towards 3 different tumour cell lines). Ref: N. Tan, et al, Chin. J. Chem., 2008, 26, 516

N O O

O

Cu O N

https://doi.org/10.1515/9783110653908-002

78

5 Pyridines and Piperidines

180 Aspernigrin B Type: Pyridine alkaloids. C27H24N2O5 Oil, [α]D20 = +37.8° (c = 0.5, DMSO). Source: Marine-derived fungus Aspergillus niger from sponge Axinella damicornis. Pharm: Neuroprotective (efficiently preventing glutamic acid-caused neuronal cell death, potent). Ref: J. Hiort, et al, JNP, 2004, 67, 1532; 2005, 68, 1821 O

O NH2

N O O O

181 Caerulomycin A Caerulomycin Type: Pyridine alkaloids. C12H11N3O2 Needles, mp 175 °C. Source: Marinederived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China, first time from marine source), terrestrial streptomycete (Streptomyces caeruleus), terrestrial bacterium (Nocardiopsis cirriefficiens). Pharm: Cytotoxic (HL60, IC50 = 0.71 μmol/L; K562, IC50 > 50 μmol/L; A549, IC50 = 0.26 μmol/L; KB, IC50 > 50 μmol/L); antibacterial (Escherichia coli, MIC = 10.9 μmol/L; Pseudomonas aeruginosa, MIC = 21.8 μmol/L); antifungal (Candida albicans, MIC = 21.8 μmol/L). Ref: A. Funk, et al, Can. J. Microbiol., 1959, 5, 317│P. Fu, et al, JNP, 2011, 74, 1751 O N N N OH

H

182 Caerulomycinamide Type: Pyridine alkaloids. C12H11N3O2 Source: Marine-derived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China). Pharm: Cytotoxic (HL60 and A549, IC50 > 50 μmol/L). Ref: P. Fu, et al, JNP, 2011, 74, 1751 O N N NH2 O

5.1 Pyridine Alkaloids

79

183 Caerulomycin C Type: Pyridine alkaloids. C13H13N3O3 Prisms (EtOH), mp 208–210 °C. Source: Marinederived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China, first time from marine source), terrestrial bacterium (Streptomyces caeruleus). Pharm: Cytotoxic (HL60, IC50 > 50 μmol/L; K562, IC50 = 1.8 μmol/L; A549, IC50 > 50 μmol/L; KB, IC50 = 3.1 μmol/L); antibacterial (Escherichia coli, MIC = 9.7 μmol/L; Pseudomonas aeruginosa, MIC = 38.6 μmol/L); antifungal (Candida albicans, MIC = 19.3 μmol/L). Ref: A. G. McInnes, et al, Can. J. Chem., 1977, 55, 4159│P. Fu, et al, JNP, 2011, 74, 1751 O

O N N

N OH

H

184 Caerulomycin F Type: Pyridine alkaloids. C12H12N2O2 White amorph. powder. Source: Marinederived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China). Pharm: Cytotoxic (HL60, IC50 > 50 μmol/L; K562, IC50 = 15.7 μmol/L; A549, IC50 > 50 μmol/L; KB, IC50 > 50 μmol/L). Ref: P. Fu, et al, JNP, 2011, 74, 1751 O

H N N

OH

185 Caerulomycin G Type: Pyridine alkaloids. C13H14N2O3 Colorless needles (MeOH), mp 127 °C. Source: Marine-derived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China). Pharm: Cytotoxic (HL60 and A549, IC50 > 50 μmol/L). Ref: P. Fu, et al, JNP, 2011, 74, 1751 O

O N N

OH

186 Caerulomycin H Type: Pyridine alkaloids. C11H9N3O2 White amorph. powder. Source: Marine-derived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China). Pharm:

80

5 Pyridines and Piperidines

Cytotoxic (HL60, IC50 = 1.6 μmol/L; A549, IC50 = 8.4 μmol/L). Ref: P. Fu, et al, JNP, 2011, 74, 1751 OH N N N OH

187 Caerulomycin I Type: Pyridine alkaloids. C13H13N3O3 Colorless needles (MeOH), mp 101 °C. Source: Marine-derived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China). Pharm: Cytotoxic (HL60, IC50 > 50 μmol/L; K562, IC50 = 0.37 μmol/L; A549, IC50 > 50 μmol/L; KB, IC50 = 5.2 μmol/L). Ref: P. Fu, et al, JNP, 2011, 74, 1751 O N N

H N O

O

188 Caerulomycin J Type: Pyridine alkaloids. C13H13N3O2 Yellow oil. Source: Marine-derived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China). Pharm: Cytotoxic (HL60, IC50 > 50 μmol/L; K562, IC50 = 15.0 μmol/L; A549, IC50 > 50 μmol/L; KB, IC50 = 25.7 μmol/L). Ref: P. Fu, et al, JNP, 2011, 74, 1751 OH N O N N H

189 Caerulomycin K Type: Pyridine alkaloids. C13H12N2O2 Colorless needles (MeOH), mp 153 °C. Source: Marine-derived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China). Pharm: Cytotoxic (HL60, K562, A549 and KB, all IC50s > 50 μmol/L). Ref: P. Fu, et al, JNP, 2011, 74, 1751

5.1 Pyridine Alkaloids

81

O

N N OH

190 Caerulomycinonitrile Type: Pyridine alkaloids. C12H9N3O Source: Marine-derived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China). Pharm: Cytotoxic (HL60, IC50 > 50 μmol/L; K562, IC50 = 15.0 μmol/L; A549, IC50 > 50 μmol/L; KB, IC50 > 50 μmol/L). Ref: P. Fu, et al, JNP, 2011, 74, 1751 O N N CN

191 1-Carboxymethylnicotinic acid Type: Pyridine alkaloids. C8H7NO4 Source: Sponge Anthosigmella cf. raromicrosclera (Japan waters). Pharm: Papain inhibitor (IC50 = 80 mg/mL); cysteine protease inhibitor. Ref: S. Matsunaga, et al, JNP, 1998, 61, 671 O O

H

+

N

O

–

O

192 CPB48-974-7 Type: Pyridine alkaloids. C18H30N2O Source: Sponge Amphimedon sp. Pharm: Antifungal (yeast Candida albicans ATCC 90028, MIC = 16 μg/mL; Cryptococcus neoformans ATCC 900112, MIC = 16 μg/mL; Aspergillus niger ATCC 40406, MIC = 4 μg/mL; Paecilomyces variotii YM-1, MIC = 16 μg/mL; Trichophyton mentagrophytes ATCC 40769, MIC > 33 μg/mL); antibacterial (Staphylococcus aureus 209P, MIC = 2 μg/mL; Micrococcus luteus IFM 2066, MIC = 8 μg/mL; Bacillus subtilis PCI 189, MIC = 8 μg/mL; Corynebacterium xerosis IFM 2057, MIC = 4 μg/mL; Escherichia coli NIJ JC2, MIC > 33 μg/mL). Ref: K. Hirano, et al, CPB, 2000, 48, 974

82

5 Pyridines and Piperidines

N

OH

N

193 CPB48-974-8 Type: Pyridine alkaloids. C17H28N2O Source: Sponge Amphimedon sp. Pharm: Antifungal (yeast Candida albicans ATCC 90028, MIC = 33 μg/mL; Cryptococcus neoformans ATCC 900112, MIC = 16 μg/mL; Aspergillus niger ATCC 40406, MIC = 8 μg/mL; Paecilomyces variotii YM-1, MIC = 16 μg/mL; Trichophyton mentagrophytes ATCC 40769, MIC = 16 μg/mL); antibacterial (Staphylococcus aureus 209P, MIC = 16 μg/mL; Micrococcus luteus IFM 2066, MIC = 16 μg/mL; Bacillus subtilis PCI 189, MIC = 16 μg/mL; Corynebacterium xerosis IFM 2057, MIC = 8 μg/mL; Escherichia coli NIJ JC2, MIC > 33 μg/mL). Ref: K. Hirano, et al, CPB, 2000, 48, 974 N

OH

N

194 Cribochaline A Hachijodine C Type: Pyridine alkaloids. C19H34N2O [α]D24 = −1.0° (c = 0.2, MeOH). Source: Sponges Xestospongia sp. and Cribochalina sp. (Ant Atoll, Pohnpei I., Federated States of Micronesia). Pharm: Antifungal (disk-diffusion assay, 300 μg/ disk: Candida albicans ATCC 14503, IZD = 14 mm; FRCA 96-489, IZD = 11 mm; Candida albicans UCD-FR1, IZD = 17 mm; Candida krusei, IZD = 14 mm (100 μg/ disk); Candida glabrata, IZD = 15 mm). Ref: G. M. Nicholas, et al, Tetrahedron, 2000, 56, 2921│S. Tsukamoto, et al, JNP, 2000, 63, 682 H N

O

N

195 Cribrochalinamine oxide A Type: Pyridine alkaloids. C21H36N2O Source: Sponge Cribrochalina sp. (Japan waters). Pharm: Antifungal. Ref: S. Matsunaga, et al, Tet. Lett., 1993, 34, 5953 O 13

N 14

N

– +

5.1 Pyridine Alkaloids

83

196 Cribrochalinamine oxide B Type: Pyridine alkaloids. C23H38N2O Source: Sponge Cribrochalina sp. (Japan waters). Pharm: Antifungal. Ref: S. Matsunaga, et al, Tet. Lett., 1993, 34, 5953 N O

N

+ –

197 Cyanogriside A Type: Pyridine alkaloids. C19H21N3O7 Source: Marine-derived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China). Pharm: Cytotoxic (MTT assay, K562, IC50 = 1.2 μmol/L; KB, IC50 = 4.7 μmol/L; MCF7, IC50 = 9.8 μmol/L). Ref: P. Fu, et al, Org. Lett., 2011, 13, 5948 O HO

O O O

O

N N 12E

N OH

198 Cyanogriside B Type: Pyridine alkaloids. C19H22N2O7 Source: Marine-derived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China). Pharm: Cytotoxic (three HTCLs, moderate); MDR reversing activity (10 μmol/L: adriamycin-induced resistance of K562/A02, reversal fold = 1.7; adriamycin-induced resistance of MCF7/Adr, reversal fold = 1.2; vincristine-induced resistance of KB/VCR, reversal fold = 3.6). Ref: P. Fu, et al, Org. Lett., 2011, 13, 5948 O HO

O O O

O

N N OH

84

5 Pyridines and Piperidines

199 Cyanogriside C Type: Pyridine alkaloids. C18H19N3O7 Source: Marine-derived actinomycete Actinoalloteichus cyanogriseus (sediment, Weihai, China). Pharm: Cytotoxic (MTT assay, K562, IC50 = 0.73 μmol/L; KB, IC50 = 4.7 μmol/L). Ref: P. Fu, et al, Org. Lett., 2011, 13, 5948 HO HO

O O O

O

N N 12E

N OH

200 Cyclostellettamine A Type: Pyridine alkaloids. C34H56N22+ mp 221–223 °C. Source: Sponge Stelletta maxima (Japan waters). Pharm: Blocks binding of [3H]-methyl quinuclidinyl benzilate (QNB) to muscarinic receptor (subtype M1 (rat brain) IC50 = 0.068 μg/mL, M2 (rat heart) IC50 = 0.026 μg/mL, M3 (rat salivary gland) IC50 = 0.071 μg/mL). Ref: N. Fusetani, et al, Tet. Lett., 1994, 35, 3967│M .J. Wanner et al, EurJOC, 1998, 889│J. E. Baldwin, et al, Tetrahedron, 1998, 54, 13655

+

N

+

N

201 Cyclostellettamine B Type: Pyridine alkaloids. C35H58N22+ mp 222–224 °C. Source: Sponge Stelletta maxima (Japan waters). Pharm: Blocks binding of [3H]-methyl quinuclidinyl benzilate (QNB) to muscarinic receptor (subtype M1 (rat brain) IC50 = 0.081 μg/mL, M2 (rat heart) IC50 = 0.031 μg/mL, M3 (rat salivary gland) IC50 = 0.109 μg/mL). Ref: N. Fusetani, et al, Tet. Lett., 1994, 35, 3967│M .J. Wanner et al, EurJOC, 1998, 889│J. E. Baldwin, et al, Tetrahedron, 1998, 54, 13655

N

N

+

2

+

5.1 Pyridine Alkaloids

85

202 Cyclostellettamine C Type: Pyridine alkaloids. C36H60N22+ mp 233–236 °C. Source: Sponge Stelletta maxima (Japan waters). Pharm: Blocks binding of [3H]-methyl quinuclidinyl benzilate (QNB) to muscarinic receptor (subtype M1 (rat brain) IC50 = 0.121 μg/mL, M2 (rat heart) IC50 = 0.054 μg/mL, M3 (rat salivary gland) IC50 = 0.144 μg/mL). Ref: N. Fusetani, et al, Tet. Lett., 1994, 35, 3967│R. D. Charan, et al, Tetrahedron, 1996, 52, 9111│M .J. Wanner et al, EurJOC, 1998, 889│J. E. Baldwin, et al, Tetrahedron, 1998, 54, 13655

+

+

N

N

203 Cyclostellettamine D Type: Pyridine alkaloids. C36H60N22+ mp 188–192 °C. Source: Sponge Stelletta maxima (Japan waters). Pharm: Blocks binding of [3H]-methyl quinuclidinyl benzilate(QNB) to muscarinic receptor (subtype M1 (rat brain) IC50 = 0.174 μg/mL, M2 (rat heart) IC50 = 0.059 μg/mL, M3 (rat salivary gland) IC50 = 0.211 μg/mL). Ref: N. Fusetani, et al, Tet. Lett., 1994, 35, 3967│M .J. Wanner et al, EurJOC, 1998, 889│J. E. Baldwin, et al, Tetrahedron, 1998, 54, 13655

+

N

+

N

204 Cyclostellettamine E Type: Pyridine alkaloids. C37H62N22+ mp 222–224 °C. Source: Sponge Stelletta maxima (Japan waters). Pharm: Blocks binding of [3H]-methyl quinuclidinyl benzilate(QNB) to muscarinic receptor (subtype M1 (rat brain) IC50 = 0.212 μg/mL, M2 (rat heart) IC50 = 0.133 μg/mL, M3 (rat salivary gland) IC50 = 0.257 μg/mL). Ref: N. Fusetani, et al, Tet. Lett., 1994, 35, 3967│M .J. Wanner et al, EurJOC, 1998, 889│J. E. Baldwin, et al, Tetrahedron, 1998, 54, 13655

2

N

N

+

3

+

86

5 Pyridines and Piperidines

205 Cyclostellettamine F Type: Pyridine alkaloids. C38H64N22+ mp 227–231 °C. Source: Sponge Stelletta maxima (Japan waters). Pharm: Blocks binding of [3H]-methyl quinuclidinyl benzilate(QNB) to muscarinic receptor (subtype M1 (rat brain) IC50 = 0.364 μg/mL, M2 (rat heart) IC50 = 0.150 μg/mL, M3 (rat salivary gland) IC50 = 0.474 μg/mL). Ref: N. Fusetani, et al, Tet. Lett., 1994, 35, 3967│M .J. Wanner et al, EurJOC, 1998, 889│J. E. Baldwin, et al, Tetrahedron, 1998, 54, 13655

N

N

+

+

206 Didymellamide A Type: Pyridine alkaloids. C24H29NO7 Source: Marine-derived fungus Stagonosporopsis cucurbitacearum from an unidentified sponge (Atami-shi, Shizuoka Prefecture, Japan). Pharm: Antifungal (inhibited growth of several pathogenic fungi including azole-resistant Candida albicans). Ref: A. Haga, et al, JNP, 2013, 76, 750

H H

O

OH HO

O

H

O O

N OH

207 Echinoclathrine A Type: Pyridine alkaloids. C22H33N2O2 Amorph. solid (hexane/EtOAc), mp 143–144 °C. Source: Sponge Echinoclathria sp. (Okinawa). Pharm: Immunosuppressive (in a mixed lymphocyte reaction assay, IC50 = 7.9 μg/mL); cytotoxic (P388, A549, HT29, all IC50s = 10 μg/mL). Ref: A. Kitamura, et al, Tetrahedron, 1999, 55, 2487 OH

N H

O 8

N

208 Echinoclathrine B Type: Pyridine alkaloids. C27H38N2O3S Amorph. solid (hexane/EtOAc), mp 135–136 °C. Source: Sponge Echinoclathria sp. (Okinawa). Pharm: Immunosuppressive (in a mixed

5.1 Pyridine Alkaloids

87

lymphocyte reaction assay, IC50 = 9.7 μg/mL). Ref: A. Kitamura, et al, Tetrahedron, 1999, 55, 2487 OH

O S

N H

12

O N

209 Echinoclathrine C Type: Pyridine alkaloids. C25H32N2O2S Amorph. solid (hexane/EtOAc), mp 121–122 °C. Source: Sponge Echinoclathria sp. (Okinawa). Pharm: Immunosuppressive (weakly). Ref: A. Kitamura, et al, Tetrahedron, 1999, 55, 2487 OH

N H

O SH 12

N

210 Glucopiericidin C Type: Pyridine alkaloids. C30H45NO8 Source: Marine-derived streptomycete Streptomyces sp. (sediment, Laguna de Terminos, Gulf of Mexico) Pharm: Antifungal (Mucor miehei); cytotoxic (number of HTCLs cells). Ref: K. A. Shaaban, et al, J. Antibiot., 2011, 64, 205 OH

HO HO HO

O

O

O

OH

N

211 Haliclamine C Type: Pyridine alkaloids. C30H54N2 Source: Sponge Haliclona viscosa (Psychrophilic, cold water, Arctic). Pharm: Antibacterial (strong inhibition of two sympatric bacterial strains). Ref: C. A. Volk, et al, EurJOC, 2004, 3154│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)

88

5 Pyridines and Piperidines

N N

212 Haliclamine D Type: Pyridine alkaloids. C31H56O2 Source: Marine acoel flatworm Prostheceraeus villatus (psychrophilic, cold water, waters off Bergen, Norway), ascidian Clavelina lepadiformis. Pharm: Antibacterial (strong inhibition of two sympatric bacterial strains). Ref: C. A. Volk, et al, EurJOC, 2004, 3154│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) N N

213 Haliclona 3-Alkylpyridinium dimer Type: Pyridine alkaloids. C32H48N22+ Source: Sponge Haliclona sp. (Pacific Coast, Guatemala). Pharm: Cytotoxic (J774.A1, HEK-293 and WEHI-164, all IC50s > 20 μg/ mL). Ref: A. Casapullo, et al, JNP, 2009, 72, 301

5 +

N

+

N

5

214 Haliclona 3-Alkylpyridinium trimer Type: Pyridine alkaloids. C48H72N33+ Source: Sponge Haliclona sp. (Pacific Coast, Guatemala). Pharm: Cytotoxic (J774.A1, HEK-293 and WEHI-164, all IC50s > 20 μg/mL). Ref: A. Casapullo, et al, JNP, 2009, 72, 301 N

+

7

+

N

7

N

+

4

5.1 Pyridine Alkaloids

89

215 Haminol 1 Type: Pyridine alkaloids. C17H23NO Source: Cephalaspids Haminoea orbignyana (Spain) and Haminoea fusari (Fusaro Lake, Gulf of Naples). Pharm: Alarm pheromone. Ref: A. Spinella, et al, Tetrahedron, 1993, 49, 1307 OH 8 9

N

216 Haminol 2 Type: Pyridine alkaloids. C19H25NO2 [α]D20 = −19° (c = 1.3, MeOH). Source: Cephalaspids Haminoea orbignyana (Spain) and Haminoea fusari (Fusaro Lake, Gulf of Naples). Pharm: Alarm pheromone. Ref: A. Spinella, et al, Tetrahedron, 1993, 49, 1307 O O

N

217 Haminol 3 Type: Pyridine alkaloids. C17H25NO Source: Cephalaspid Haminoea fusari (Fusaro Lake, Gulf of Naples). Pharm: Alarm pheromone. Ref: A. Spinella, et al, Tetrahedron, 1993, 49, 1307 OH

N

218 Haminol 4 Type: Pyridine alkaloids. C19H27NO2 [α]D20 = −12.5° (c = 0.7, MeOH). Source: Cephalaspid Haminoea fusari (Fusaro Lake, Gulf of Naples). Pharm: Alarm pheromone. Ref: A. Spinella, et al, Tetrahedron, 1993, 49, 1307 O O

N

90

5 Pyridines and Piperidines

219 Haminol 5 Type: Pyridine alkaloids. C17H23NO Source: Cephalaspid Haminoea fusari (Fusaro Lake, Gulf of Naples). Pharm: Alarm pheromone. Ref: A. Spinella, et al, Tetrahedron, 1993, 49, 1307 OH

N

220 Haminol 6 Type: Pyridine alkaloids. C19H25NO2 [α]D20 = −4.2° (c = 0.2, MeOH). Source: Cephalaspid Haminoea fusari (Fusaro Lake, Gulf of Naples). Pharm: Alarm pheromone. Ref: A. Spinella, et al, Tetrahedron, 1993, 49, 1307 O O

N

221 Haminol A Type: Pyridine alkaloids. C17H23NO Oil, mp 144–145 °C, [α]D25 = +5.0° (c = 0.3, MeOH). Source: Cephalaspids Haminoea orteai (Spain) and Haminoea navicula. Pharm: Cytotoxic (leukemia); alarm pheromone. Ref: H. L. Sleeper, et al, JACS, 1977, 99, 2367│G. Cimino, et al, Experientia, 1991, 47, 61│A. Spinella, et al, Tetrahedron, 1993, 49, 1307│J. Matikainen, et al, Synth. Commun., 1995, 25, 195│J. Matikainen, et al, JNP, 1995, 58, 1622│R, Alvarez, et al, Tetrahedron: Asymmetry, 1998, 9, 3065│R. Alvarez, et al, Tetrahedron, 1998, 54, 6793 OH

N

222 Haminol B Type: Pyridine alkaloids. C19H25NO2 Oil, mp 125–140 °C, [α]D25 = −24.0° (c = 0.4, MeOH). Source: Cephalaspids Haminoea orteai (Spain), Haminoea navicula and Navanax inermis. Pharm: Alarm pheromone. Ref: H. L. Sleeper, et al, JACS, 1977, 99, 2367│G. Cimino, et al, Experientia, 1991, 47, 61│A. Spinella, et al, Tetrahedron,

5.1 Pyridine Alkaloids

91

1993, 49, 1307│J. Matikainen, et al, Synth. Commun., 1995, 25, 195│J. Matikainen, et al, JNP, 1995, 58, 1622│R, Alvarez, et al, Tetrahedron: Asymmetry, 1998, 9, 3065│R. Alvarez, et al, Tetrahedron, 1998, 54, 6793 O O

N

223 Haminol C Type: Pyridine alkaloids. C19H25NO2 mp 135–137 °C. Source: Cephalaspids Haminoea orteai (Spain), Haminoea navicula and Navanax inermis. Pharm: Alarm pheromone. Ref: H. L. Sleeper, et al, JACS, 1977, 99, 2367│G. Cimino, et al, Experientia, 1991, 47, 61│A. Spinella, et al, Tetrahedron, 1993, 49, 1307│R, Alvarez, et al, Tetrahedron: Asymmetry, 1998, 9, 3065│R. Alvarez, et al, Tetrahedron, 1998, 54, 6793 O O N

224 Homarine 2-Carboxy-1-methylpyridinium betaine Type: Pyridine alkaloids. C7H7NO2 Cryst. (EtOH). Source: Red alga Pterocladia capillacea, gorgonians Leptogorgia setacea and Leptogorgia virgulata, lobsters Homarus vulgaris and Homarus americanus, soft coral Gersemia Antarctica (Antarctic), gastropod Marseniopsis mollis (Antarctic). Pharm: Antifoulant; antibacterial; antifeedant (feeding deterrent in marine organisms). Ref: N. M. Targett, et al, J. Chem. Ecol. 1983, 9, 817│CRC Press, DNP on DVD, 2012, version 20.2

–

N

O

+

O

225 Ikimine A Type: Pyridine alkaloids. C19H32N2O Oil. Source: An unidentified sponge (Federated States of Micronesia). Pharm: Cytotoxic (KB, IC50 = 5 μg/mL); antibacterial; antifungal. Ref: A,. R. Carroll, et al, Tetrahedron, 1990, 46, 6637│F. Bracher, et al, Nat. Prod. Lett., 1994, 4, 223

92

5 Pyridines and Piperidines

N N

O

226 Ikimine B β-Methyl-3-pyridinedodecanal O-methyloxime Type: Pyridine alkaloids. C19H32N2O Oil. Source: An unidentified sponge. Pharm: Cytotoxic (KB, IC50 = 7 μg/mL). Ref: A. R. Carroll, et al, Tetrahedron, 1990, 46, 6637│S. P. Romeril, et al, Tet. Lett., 2004, 45, 3273 N

O

N

227 Ikimine C Type: Pyridine alkaloids. C19H34N2O Oil. Source: Sponge Niphates sp., other sponges. Pharm: Cytotoxic (KB, IC50 = 5 μg/mL). Ref: A. R. Carroll, et al, Tetrahedron, 1990, 46, 6637

N H

O

N

228 Ikimine D Type: Pyridine alkaloids. C20H32N2O Oil. Source: An unidentified sponge. Pharm: Cytotoxic (KB, IC50 = 5–10 μg/mL). Ref: A. R. Carroll, et al, Tetrahedron, 1990, 46, 6637

O NH

N

229 (–)-Isopuloupone Type: Pyridine alkaloids. C21H27NO [α]D20 = −111.9° (c = 0.4, n-hexane). Source: Cephalaspid Navanax inermis and its prey cephalaspid Bulla gouldiana. Pharm: Ichthyotoxic; LD50 (mosquito fish Gambusia affinis and brine shrimp Artemia salina) = 2.2 ppm. Ref: A. Spinella, et al, Tetrahedron, 1993, 49, 3203│J. Matikainen, et al, Synth. Commun., 1995, 25, 195│J. Matikainen, et al, JNP, 1995, 58, 1622

5.1 Pyridine Alkaloids

93

H

N O

H

230 Methyl-3,4,5-trimethoxy-2-(2-(nicotinamido)benzamido)benzoate Type: Pyridine alkaloids. C24H23N3O7 Needles (MeOH), mp 141–143 °C. Source: Marine-derived fungus Aspergillus terreus PT06-2 (Grown in High Salt Medium 10% salinity). Pharm: Antibacterial (Staphylococcus aureus, MIC = 52.4 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 O O

O

O N H

NH O

O

O N

231 Navenone A Type: Pyridine alkaloids. C15H15NO Yellow cryst. (C6H6), mp 144–145 °C. Source: Cephalaspid Navanax inermis [Syn. Chelidonura inermis] (major constituent) Pharm: Alarm pheromone. Ref: H. L. Sleeper, et al, J. Chem. Ecol., 1980, 6, 57 O

N

232 Nemertelline Type: Pyridine alkaloids. C20H14N4 Crystals (Et2O), mp 154–156 °C. Source: Nemertinean Aphiporus angulatus. Pharm: Neurotoxin. Ref: W. R. Kem, et al, Experientia, 1976, 32, 684.│J. A. Zoltewicz, et al, Tetrahedron, 1995, 51, 11 401│M. P. Cruskie Jr., et al, JOC, 1995, 60, 7491

94

N

5 Pyridines and Piperidines

N

N

N

233 Nicotinamide Vitamin B3 Type: Pyridine alkaloids. C6H6N2O Needles (C6H6), mp 129–130 °C, bp0.0005 mmHg 150–160 °C. Source: An unidentified marine bacterium He159b, also widespread in plants, yeast and fungi. Pharm: Enzyme cofactor, used in treatment of pellagra. Ref: CRC Press, DNP on DVD, 2012, version 20.2 O NH2 N

234 Niphatesine A Type: Pyridine alkaloids. C19H30N2 Oil. Source: Sponge Niphates sp. Pharm: Antineoplastic. Ref: A. V. R. Rao, et al, Tet. Lett., 1993, 34, 8329│J. Kobayashi, et al, JCS Perken I, 1990, 3301 NH2

N

235 Niphatesine B Type: Pyridine alkaloids. C21H34N2 Oil. Source: Sponge Niphates sp. Pharm: Antineoplastic. Ref: A. V. R. Rao, et al, Tet. Lett., 1993, 34, 8329│J. Kobayashi, et al, JCS Perken I, 1990, 3301 NH2

N

236 (S)-Niphatesine C Type: Pyridine alkaloids. C18H32N2 Oil, [α]D25 = +9.4° (c = 0.053, MeOH). Source: Sponge Niphates sp. Pharm: Antineoplastic. Ref: J. Kobayashi, et al, JCS Perkin I, 1990, 3301

5.1 Pyridine Alkaloids

95

NH2 N

237 Niphatesine D Type: Pyridine alkaloids. C18H33N2 Oil, [α]D25 = +4.4° (c = 0.045, MeOH). Source: Sponge Niphates sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 0.95 μg/mL). Ref: J. Kobayashi, et al, JCS Perken I, 1990, 3301│A. V. R. Rao, et al, Tet. Lett., 1993, 34, 8329│N. Fusetani, et al, Tet. Lett., 1994, 35, 3967 NH2 N

238 Niphatesine E Type: Pyridine alkaloids. C20H30N2O Oil, mixture of 1.4:1 of E and Z isomers. Source: Sponge Niphates sp. (Okinawa). Pharm: Cytotoxic (L1210, KB); antifungal; antibacterial (gram-positive bacteria). Ref: J. Kobayashi, et al, JCS Perkin I, 1992, 1291 O N H N

239 Niphatesine F Type: Pyridine alkaloids. C22H34N2O Oil, mixture of 1.7:1 of E and Z isomers. Source: Sponge Niphates sp. (Okinawa). Pharm: Cytotoxic (L1210, KB); antifungal; antibacterial (gram-positive bacteria). Ref: J. Kobayashi, et al, JCS Perkin I, 1992, 1291 O N H N

240 Niphatesine G Type: Pyridine alkaloids. C20H34N2O Oil, mixture of 3.2:1 of E and Z isomers. Source: Sponge Niphates sp. (Okinawa). Pharm: Cytotoxic (L1210, KB); antifungal; antibacterial (gram-positive bacteria). Ref: J. Kobayashi, et al, JCS Perkin I, 1992, 1291

96

5 Pyridines and Piperidines

H N

O

N

241 Niphatesine H Type: Pyridine alkaloids. C20H32N2O Oil. Source: Sponge Niphates sp. (Okinawa). Pharm: Cytotoxic; antimicrobial. Ref: J. Kobayashi, et al, JCS Perkin I, 1992, 1291 H

O

N

N

242 Niphatoxin A Type: Pyridine alkaloids. C35H48N31+ Source: Sponge Niphates sp. (Red Sea). Pharm: Cytotoxic; ichthyotoxin. Ref: R. Talpir, et al, Tet. Lett., 1992, 33, 3033

N

+

N

N

243 Niphatoxin B Type: Pyridine alkaloids. C36H50N31+ Source: Sponge Niphates sp. (Red Sea). Pharm: Cytotoxic (P388, IC50 = 0.1 μg/mL); ichthyotoxic. Ref: R. Talpir, et al, Tet. Lett., 1992, 33, 3033

N

+

N

N

244 Niphatyne A N-Methoxy-16-(3-pyridinyl)-7-hexadecyn-1-amine Type: Pyridine alkaloids. C22H36N2O Source: Sponge Niphates sp. Pharm: Cytotoxic (P388, IC50 = 0.5 μg/mL). Ref: E. Quiñoà, et al, Tet. Lett., 1987, 28, 2467

5.1 Pyridine Alkaloids

H N

97

O

N

245 Niphatyne B N-Methoxy-16-(3-pyridinyl)-5-hexadecyn-1-amine Type: Pyridine alkaloids. C22H36N2O Source: Sponge Niphates sp. Pharm: Cytotoxic. Ref: E. Quiñoà, et al, Tet. Lett., 1987, 28, 2467

O

NH

N

246 Njaoaminium A Type: Pyridine alkaloids. C30H44N22+ Oil. Source: Sponge Reniera sp. (Pemba I., Tanzania). Pharm: Cytotoxic (A549, HT29 and MDA-MB-231, all GI50s > 10 μmol/L). Ref: R. Laville, et al, Molecules, 2009, 14, 4716

4

N

N

+

+

4

247 Njaoaminium B Type: Pyridine alkaloids. C32H48N22+ Oil, [α]D24 = −9.4° (c = 0.11, MeOH). Source: Sponge Reniera sp. (Pemba I., Tanzania). Pharm: Cytotoxic (A549, GI50 = 4.1 μmol/L, HT29, GI50 = 4.2 μmol/L, MDA-MB-231, GI50 = 4.8 μmol/L). Ref: R. Laville, et al, Molecules, 2009, 14, 4716

4

N

N

+

+

4

248 Njaoaminium C Type: Pyridine alkaloids. C31H46N22+ Oil, [α]D24 = −13.3° (c = 0.09, MeOH). Source: Sponge Reniera sp. (Pemba I., Tanzania). Pharm: Cytotoxic (A549, HT29 and MDAMB-231, all GI50s > 10 μmol/L). Ref: R. Laville, et al, Molecules, 2009, 14, 4716

98

5 Pyridines and Piperidines

4

N

N

+

+

4

249 Petrosaspongiolide L Type: Pyridine alkaloids. C24H35NO2 [α]D25 = −33.3° (c = 0.001, CHCl3). Source: Sponge Petrosaspongia nigra (New Caledonia). Pharm: Cytotoxic (NSCLC-N6, IC50 = 5.7 μg/mL). Ref: L. G. Paloma, et al, Tetrahedron, 1997, 53, 10451 N

HOOC

250 Pileotin B Type: Pyridine alkaloids. C30H33NO7 Source: Marine-derived fungus Aspergillus fumigatus from urchin Toxopneustes pileolus. Pharm: Cytotoxic (P388, moderate). Ref: M. Kitano, et al, Tet. Lett., 2012, 53, 4192 N

OH O O

H

O O

HO

O

251 Pyridinebetaine A Type: Pyridine alkaloids. C8H9NO3 Source: Sponge Agelas dispar (Bahamas). Pharm: Antibacterial (gram-positive bacteria, Bacillus subtilis, MIC = 3.5 μg/mL, Staphylococcus aureus, MIC = 5.0 μg/mL). Ref: F. Cafieri, et al, JNP, 1998, 61, 1171 O O N

+

OH

–

5.1 Pyridine Alkaloids

99

252 Pyrinodemin A Type: Pyridine alkaloids. C38H59N3O Oil, [α]D25 = −9° (c = 1, CHCl3). Source: Sponge Amphimedon sp. Pharm: Cytotoxic (L1210, IC50 = 0.058 μg/mL, KB, IC50 = 0.5 μg/mL); antifungal (yeast Candida albicans ATCC 90028, MIC > 33 μg/mL; Cryptococcus neoformans ATCC 900112, MIC = 33 μg/mL; Aspergillus niger ATCC 40406, MIC = 33 μg/ mL; Paecilomyces variotii YM-1, MIC = 33 μg/mL; Trichophyton mentagrophytes ATCC 40769, MIC > 33 μg/mL); antibacterial (Staphylococcus aureus 209P, MIC > 33 μg/mL; Micrococcus luteus IFM 2066, MIC > 33 μg/mL; Bacillus subtilis PCI 189, MIC > 33 μg/ mL; Corynebacterium xerosis IFM 2057, MIC > 33 μg/mL; Escherichia coli NIJ JC2, MIC > 33 μg/mL). Ref: M． Tsuda， et al，Tet. Lett., 1999, 40, 4819│K. Hirano, et al, CPB, 2000, 48, 974│B. B. Snider, et al, Tet. Lett., 2001, 42, 1639│H. Ishiyama, Molecules, 2005, 10, 312

H

H 7

O

N

N 6

4

N

253 Pyrinodemin B Type: Pyridine alkaloids. C37H59N3O Source: Sponge Amphimedon sp. Pharm: Cytotoxic (L1210, IC50 = 0.07 μg/mL; KB, IC50 = 0.5 μg/mL). Ref: K. Hirano, et al, CPB, 2000, 48, 974│S. P. Romeril, et al, Tet. Lett., 2003, 44, 7757

H

H N

N O

7

5

5

N

254 Pyrinodemin C Type: Pyridine alkaloids. C37H57N3O Source: Sponge Amphimedon sp. Pharm: Cytotoxic (L1210, IC50 = 0.06 μg/mL; KB, IC50 = 0.5 μg/mL). Ref: K. Hirano, et al, CPB, 2000, 48, 974│S. P. Romeril, et al, Tet. Lett., 2003, 44, 7757

H 7

N

H N

N O

3

8

100

5 Pyridines and Piperidines

255 Pyrinodemin D Type: Pyridine alkaloids. C36H57N3O Source: Sponge Amphimedon sp. Pharm: Cytotoxic (L1210, IC50 = 0.08 μg/mL; KB, IC50 = 0.5 μg/mL). Ref: K. Hirano, et al, CPB, 2000, 48, 974│S. P. Romeril, et al, Tet. Lett., 2003, 44, 7757

H 7

H O

N

N 5

4

N

256 Streptokordin 4-Acetyl-6-methyl-2(1H)-pyridinone Type: Pyridine alkaloids. C8H9NO2 Amorph. powder. Source: Marine-derived streptomycete Streptomyces sp. KORDI-323 (psychrophilic, cold water). Pharm: Cytotoxic. Ref: S. -Y. Jeong, et al, J. Antibiot., 2006, 59, 234│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) O HN

O

257 Sulcatin Type: Pyridine alkaloids. C10H13NO2 Amorphous solid. Source: Ascidian Microcosmus vulgaris [Syn. Microcosmus sulcatus] (depth of 40 m, Bay of Naples, Procida, Punta Pizzaco, Italy). Pharm: Antiproliferative (in vitro, 96h, J774, IC50 ≈ 2 μg/mL, control 6Mercaptopurine, IC50 ≈ 1 μg/mL; WEHI-164, IC50 ≈ 65 μg/mL, 6-Mercaptopurine, IC50 ≈ 1.5 μg/mL). Ref: A. Aiello, et al, JNP, 2000, 63, 517 O O

–

+

N

258 Thallusin Type: Pyridine alkaloids. C25H31NO7 Amorph. powder. Source: Marine bacterium Cytophaga sp. YM2-23 from green alga Monostroma sp. Pharm: Morphogenesis inducer in algae Ref: Y. Matsuo, et al, Science (Washington, D. C.), 2005, 307, 1598

5.1 Pyridine Alkaloids

O

101

OH

N COOH COOH O H H

259 Theonelladine A Type: Pyridine alkaloids. C19H32N2 Source: Lithistid sponge Theonella swinhoei (Okinawa). Pharm: Cytotoxic (Ll210, IC50 = 4.7 μg/mL; KB, IC50 = 10 μg/mL); calcium release inducer (from sarcoplasmic reticulum, twenty times more potent than caffeine) Ref: J. Kobayashi, et al, Tet. Lett., 1989, 30, 4833│J. Kobayashi, et al, JCS Perkin I, 1990, 3301

N

NH2

260 Theonelladine B Type: Pyridine alkaloids. C20H34N2 Source: Lithistid sponge Theonella swinhoei (Okinawa). Pharm: Cytotoxic (Ll210, IC50 = 1.0 μg/mL; KB, IC50 = 3.6 μg/mL); calcium release inducer (from sarcoplasmic reticulum, twenty times more potent than caffeine) Ref: J. Kobayashi, et al, Tet. Lett., 1989, 30, 4833│J. Kobayashi, et al, JCS Perkin I, 1990, 3301

N

H N

261 Theonelladine C Type: Pyridine alkaloids. C18H32N2 Source: Lithistid sponge Theonella swinhoei (Okinawa). Pharm: Cytotoxic (Ll210, IC50 = 3.6 μg/mL; KB, IC50 = 10 μg/mL); calcium release inducer (from sarcoplasmic reticulum, twenty times more potent than caffeine) Ref: J. Kobayashi, et al, Tet. Lett., 1989, 30, 4833 NH2 N

102

5 Pyridines and Piperidines

262 Theonelladine D Type: Pyridine alkaloids. C19H34N2 Source: Lithistid sponge Theonella swinhoei (Okinawa). Pharm: Cytotoxic (Ll210, IC50 = 1.6 μg/mL; KB, IC50 = 5.2 μg/mL); calcium release inducer (from sarcoplasmic reticulum, twenty times more potent than caffeine) Ref: J. Kobayashi, et al, Tet. Lett., 1989, 30, 4833 N H N

263 Untenine A Type: Pyridine alkaloids. C19H30N2O2 Source: Sponge Callyspongia sp. (Okinawa). Pharm: Antifoulant (inhibits microfouling, IC100 = 3.0 mg/cm2). Ref: G. -Y. -S. Wang, et al, Tet. Lett., 1996, 37, 1813 N

+

–

O

O

N

264 Untenine B Type: Pyridine alkaloids. C17H28N2O2 Source: Sponge Callyspongia sp. (Okinawa). Pharm: Antifoulant (inhibits microfouling, IC100 = 6.1 mg/cm2). Ref: G. -Y. -S. Wang, et al, Tet. Lett., 1996, 37, 1813 +

–

N O O N

265 Untenine C Type: Pyridine alkaloids. C19H28N2O2 Source: Sponge Callyspongia sp. (Okinawa). Pharm: Antifoulant (inhibits microfouling, IC100 = 5.8 mg/cm2). Ref: G. -Y. -S. Wang, et al, Tet. Lett., 1996, 37, 1813 +

–

N O N

O

266 Viscosaline Type: Pyridine alkaloids. C39H66N3O21+ First acyclic dimeric 3-alkyl pyridine alkaloid from natural sources. Source: Sponge Haliclona viscosa (Psychrophilic, cold water, Kongsfjord, inlet on west coast of Spitsbergen, Svalbard, Arctic Ocean). Pharm:

5.1 Pyridine Alkaloids

103

Antibacterial. Ref: C. A. Volk, et al, Org. Biomol. Chem., 2004, 2, 1827│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)│C. Timm, et al, Mar. Drugs. 2010, 8, 483│S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev) O N H

–

O

+

N

N

267 Viscosamine Type: Pyridine alkaloids. C54H90N33+ Solid (trifluoroacetate). Source: Sponge Haliclona viscosa (Psychrophilic, cold water, Kongsfjord, inlet on west coast of Spitsbergen, Svalbard, Arctic Ocean). Pharm: Antibacterial; antifeedant (amphipod Anonyx nugax and starfish). Ref: C. A. Volk, et al, Org. Lett., 2003, 5, 3567│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)│C. Timm, et al, Mar. Drugs. 2010, 8, 483│S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev) +

N +

N

+

N

268 Xylogranatopyridine A Type: Pyridine alkaloids. C27H29NO6 Colorless crystals (CHCl3), mp 278–280 °C, [α]D20 = +210.0° (c = 0.03, MeOH). Source: Mangrove Xylocarpus granatum. Pharm: PTP1B (protein tyrosine phosphatase 1B) inhibitor (IC50 = 22.9 μmol/L, significant). Ref: Z. -F. Zhou, et al, Tetrahedron, 2014, 70, 6444

104

5 Pyridines and Piperidines

O

H O N

O

O O H

O

5.2 Piperidine Alkaloids 269 Azaspiracid 1 Killarytoxin 3 Type: Piperidine alkaloids. C47H71NO12 Amorph. solid, [α]D20 = −21° (c = 0.1, MeOH). Source: Blue mussel Mytilus edulis. Pharm: Shellfish toxin; diarrhetic. Ref: M. Satake, et al, JACS, 1998, 120, 9967│P. McCarron, et al, J. Agric. Food Chem., 2009, 57, 160

O

8

O

O

3

H OH

H

O O HO H

OH H

H N

22

O

23

O O

O H

270 Azaspiracid 2 Type: Piperidine alkaloids. C48H73NO12 Source: Blue mussel Mytilus edulis, sponge Echinoclathria sp. Pharm: Cytotoxic. Ref: K. Ofuji, et al, Nat. Toxins, 1999, 7, 99│R. Ueoka, et al, Toxicon, 2009, 53, 680

O

8

O

3

O

H OH

H

O O HO H

OH H

H N

O O

O H

22

O

23

5.2 Piperidine Alkaloids

105

271 Azaspiracid 4 Type: Piperidine alkaloids. C46H69NO13 Source: Blue mussel Mytilus edulis. Pharm: Toxin. Ref: K. Ofuji, et al, Biosci., Biotechnol., Biochem., 2001, 65, 740

O

8 3R

O OH

O

H OH

H

O

22

O HO H

OH H

H N

23

O

O O

O H

272 Azaspiracid 5 Type: Piperidine alkaloids. C46H69NO13 Source: Blue mussel Mytilus edulis. Pharm: Toxin. Ref: K. Ofuji, et al, Biosci., Biotechnol., Biochem., 2001, 65, 740

O

8

O

3

O

H OH

H

O

22

O HO H

OH H

H N

O

23S

OH

O O

O H

273 Azaspiracid 6 Type: Piperidine alkaloids. C47H71NO12 Source: Blue mussel Mytilus edulis (Bruckless, Donegal, Ireland). Pharm: Toxin. Ref: P. McCarron,et al, J. Agric. Food Chem., 2009, 57, 160│J. Kilcoyne, et al, J. Agric. Food Chem., 2012, 60, 2447 H O

8

O

3

O

OH

H

O O HO H

OH H

H N

O O

O H

O

22 23

106

5 Pyridines and Piperidines

274 Corydendramine A 6-(1,3,5,9-Dodecatetraenyl)-2-methyl-3-piperidinol Type: Piperidine alkaloids. C18H29NO Pale yellow oil, [α]D = −24.3° (c = 0.17, MeOH). Source: Hydroid Corydendrium parasiticum. Pharm: Antifeedant (fish). Ref: N. Lindquist, et al, JNP, 2000, 63, 1290 HO

N H

275 Corydendramine B Type: Piperidine alkaloids. C18H29NO White amorph. powder, [α]D = +83.7° (c = 0.083, MeOH). Source: Hydroid Corydendrium parasiticum. Pharm: Antifeedant (fish). Ref: N. Lindquist, et al, JNP, 2000, 63, 1290 HO

N H

276 Haliclonacyclamine A Type: Piperidine alkaloids. C32H56N2 Needles, mp 149–150 °C, [α]D = −3.4° (c = 1.21, CH2Cl2). Source: Sponges Haliclona sp. ( Indonesia; Great Barrier Reef). Pharm: Antibacterial (TB-causing Mycobacterium smegmatis and Mycobacterium bovis, under both aerobic and hypoxic conditions); antifungal; cytotoxic (P388, IC50 = 0.8 μg/mL). Ref: R. D. Charan, et al, Tetrahedron, 1996, 52, 9111│R. J. Clark, et al, Tetrahedron, 1998, 54, 8811│I. W. Mudianta, et al, Aust. J. Chem., 2009, 62, 667│M. Arai, et al, CPB, 2009, 57, 1136

H

H N H H

N 3

4

277 Haliclonacyclamine B Type: Piperidine alkaloids. C32H56N2 Needles, mp 145–146 °C, [α]D = +3.4° (c = 0.55, CH2Cl2). Source: Sponges Haliclona sp. ( Indonesia; Great Barrier Reef). Pharm: Antimycobacterial (TB-causing Mycobacterium smegmatis and Mycobacterium bovis, under both aerobic and hypoxic conditions); antifungal; cytotoxic (P388, IC50 = 0.6 μg/mL). Ref: R. D. Charan, et al, Tetrahedron, 1996, 52, 9111│R. J. Clark,

5.2 Piperidine Alkaloids

107

et al, Tetrahedron, 1998, 54, 8811│I. W. Mudianta, et al, Aust. J. Chem., 2009, 62, 667│M. Arai, et al, CPB, 2009, 57, 1136

H

H N H

N

H

5

2

278 Halicyclamine B Type: Piperidine alkaloids. C26H42N2 [α]D = 143.5° (c = 0.63). Source: Sponge Xestospongia sp. (Indonesia). Pharm: Antibacterial (Escherichia coli and Bacillus subtilis); cytotoxic. Ref: B. Harrison, et al, Tet. Lett., 1996, 37, 9151

H N N H

H

279 22-Hydroxyhaliclonacyclamine B Type: Piperidine alkaloids. C33H60N2O Amorph. solid, [α]D20 = +11.8° (c = 0.1, MeOH). Source: Sponge Haliclona sp. ( Indonesia). Pharm: Antimycobacterial (TBcausing Mycobacterium smegmatis and Mycobacterium bovis, under both aerobic and hypoxic conditions). Ref: M. Arai, et al, CPB, 2009, 57, 1136

H

H N H

N

H OH

280 Neopetrosiamine A Type: Piperidine alkaloids. C30H52N2 Viscous oil, [α]D20 = −10° (c = 1, CHCl3). Source: Sponge Neopetrosia proxima (Mona I., Puerto Rico). Pharm: Antimycobacterial; cytotoxic. Ref: X. Wei, et al, BoMCL, 2010, 20, 5905

108

5 Pyridines and Piperidines

H

H

N H

N

H

281 Penasulfate A Type: Piperidine alkaloids. C36H69NO11S2 Amorph. solid (di-Na salt), [α]D29 = +10° (c = 0.03, MeOH) (di-Na salt). Source: Sponge Penares sp. Pharm: α-Glucosidase inhibitor. Ref: Y. Nakao, et al, JNP, 2004, 67, 1346

O

N

O O O

O

S

OH O

12

O

S O

O OH

282 Pinnaic acid Type: Piperidine alkaloids. C23H36ClNO4 Source: Greenshell mussel Pteria muricata (viscera). Pharm: cPLA2 inhibitor (IC50 = 0.2 mmol/L; since a cytosolic 85 kDa phospholipase (cPLA2) exhibits specificity for release of arachidonic acid from membrane phospholipids, compounds that inhibit cPLA2 activity have been targeted as antiinflammatory agents). Ref: T. Chuo, et al, Tet. Lett., 1996, 37, 3871│M. W. Carson, et al, Angew. Chem., Int. Ed., 2001, 40, 4453│M. Kuramoto, et al, Mar. Drugs, 2004, 2, 39 H HO HN H

O

H OH HO

Cl

283 Pseudodistomin A Type: Piperidine alkaloids. C18H34N2O Oil (N,N’-di-Ac), [α]D24 = +36° (c = 1, MeOH) (di-Ac). Source: Ascidian Pseudodistoma kanoko (Okinawa). Pharm: Cytotoxic;

5.2 Piperidine Alkaloids

109

phosphodiesterase inhibitor; calmodulin antagonist. Ref: .M. Ishibashi, et al, JOC, 1987, 52, 450│M. Ishibashi, et al, JNP, 1995, 58, 804 OH NH2

N H

284 Pseudodistomin B Type: Piperidine alkaloids. C18H34N2O Oil (N,N’-di-Ac), [α]D24 = +35° (c = 1, MeOH) (di-Ac). Source: Ascidians Pseudodistoma kanoko (Okinawa) and Pseudodistoma megalarva (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 6.0 μg/mL; KB, IC50 = 13 μg/mL); phosphodiesterase inhibitor; calmodulin antagonist. Ref: M. Ishibashi, et al, JOC, 1987, 52, 450│I. Utsunomiya, et al, Heterocycles, 1992, 33, 349│T. Naito, et al, Tet. Lett., 1992, 33, 4033│T. Kiguchi, et al, Tet. Lett., 1992, 33, 7389 OH NH2 N H

285 Pseudodistomin C Type: Piperidine alkaloids. C20H43N2O Oil (N1,N5,O-tri-Ac), [α]D22 = +85° (c = 1, CHCl3) (tri-Ac). Source: Ascidians Pseudodistoma kanoko (Okinawa) and Pseudodistoma megalarva. Pharm: Cytotoxic (L1210, IC50 = 2.3 μg/mL; KB, IC50 = 2.6 μg/mL). Ref: J. Kobayashi, et al, JOC, 1995, 60, 6941 OH NH2 N H

286 Pseudodistomin D Type: Piperidine alkaloids. C18H34N2O Gum, [α]D25 = +5° (c = 0.26, MeOH). Source: Ascidian Pseudodistoma megalarva (Palau, Oceania). Pharm: DNA damaging activity (yeast-based assay). Ref: A. J. Freyer, et al, JNP, 1997, 60, 986

110

5 Pyridines and Piperidines

OH NH2 N H

287 Pseudodistomin E Type: Piperidine alkaloids. C18H34N2O Gum, [α]D25 = −20.8° (c = 0.39, MeOH). Source: Ascidian Pseudodistoma megalarva (Palau, Oceania). Pharm: DNA damaging activity (yeast-based assay). Ref: A. J. Freyer, et al, JNP, 1997, 60, 986 OH NH2 N H

288 Pseudodistomin F Type: Piperidine alkaloids. C20H34N2O [α]D25 = −13.9° (c = 0.42, MeOH). Source: Ascidian Pseudodistoma megalarva (Palau, Oceania). Pharm: DNA damaging activity (yeast-based assay). Ref: M. Ishibashi, et al, JOC, 1987, 52, 450│A. J. Freyer, et al, JNP, 1997, 60, 986│D. Ma, et al, JOC, 2000, 65, 6009 OH H 2N H N H

289 Sesbanimide A Sesbanimide Type: Piperidine alkaloids. C15H21NO7 Cryst. (Et2O/CH2Cl2 or MeOH/ CH2Cl2), mp 158–159 °C, mp 155–156 °C, [α]D20 = +54.7° (c = 0.17, CHCl3), [α]D20 = −5.6° (c = 0.28, MeOH). Source: Marine-derived bacterium Agrobacterium sp. PH-130 from ascidian Ecteinascidia turbinata. Pharm: Antineoplastic (P338 in vivo); cytotoxic (KB); immunosuppressant. Ref: R. G. Powell, et al, JACS, 1983, 105, 3739│C. Acebal, et al, J. Antibiot., 1998, 51, 64

OH

O

O

H

H

O O

OH

NH

5.2 Piperidine Alkaloids

111

290 Tauropinnaic acid Type: Piperidine alkaloids. C25H41ClN2O6S Source: Greenshell mussel Pteria muricata (viscera). Pharm: cPLA2 inhibitor (IC50 = 0.09 mmol/L; since a cytosolic 85 kDa phospholipase (cPLA2) exhibits specificity for release of arachidonic acid from membrane phospholipids, compounds that inhibit cPLA2 activity have been targeted as anti-inflammatory agents). Ref: M. Kuramoto, et al, Mar. Drugs, 2004, 2, 39

O HO

H

H N

S O

HN H

O

H OH HO

CI

291 Fascularine Type: Cylindricine alkaloids. C20H34N2S Gum. Source: Ascidian Nephteis fascicularis (Federated States of Micronesia). Pharm: DNA damaging activity; cytotoxic (Vero, IC50 = 14 μg/mL). Ref: A. D. Patil, et al, Tet. Lett., 1997, 38, 363

H N

N

S

292 Lepadoformine Type: Cylindricine alkaloids. C19H35NO Oil, mp 272–274 °C. Source: Ascidian Clavelina lepadiformis. Pharm: Cytotoxic (KB, IC50 = 9.2 μg/mL, HT29, IC50 = 0.75 μg/mL, P388, IC50 = 3.10 μg/mL, P388 doxorubicin-resistant, IC50 = 6.3 μg/mL, NSCLC-N6, IC50 = 6.1 μg/mL); one of the strongest neurotoxin (analgetic, local anesthetic, antispasmotic). Ref: J. F. Biard, et al, Tet. Lett., 1994, 35, 2691│K. M. Werner, et al, JOC, 1999, 64, 686; 4865│W. H. Pearson, et al, JOC, 1999, 64, 688│H. Abe, et al, Tet. Lett., 2000, 41, 1205│H. Abe, et al, JACS, 2000, 122, 4583

N HO

112

5 Pyridines and Piperidines

293 Clavepictine A Type: Quinolizidine alkaloids. C22H37NO2 Oil, [α]D = −75.6° (c = 0.7, CH2Cl2). Source: Ascidian Clavelina picta. Pharm: Antineoplastic (inhibits growth of mus leukemia and hmn solid tumor cell lines P388, A549, U251, SN12k1, IC50 = 1.8–8.5 μg/mL, and effectively kill each cell line at less than 25 μg/mL (LC50 = 10.1–24.7 μg/mL) under conventional culture conditions). Ref: M. F. Raub, et al, JACS, 1991, 113, 3178

H N

O

O

294 Clavepictine B 6-(1,3-Decadienyl)octahydro-4-methyl-2H-quinolizin-3-ol Type: Quinolizidine alkaloids. C20H35NO Cryst., mp 70–72 °C, [α]D = +27.1° (c = 0.03, CH2Cl2). Source: Ascidian Clavelina picta. Pharm: Antineoplastic (inhibits growth of mus leukemia and hmn solid tumor cell lines P388, A549, U251, SN12k1, IC50 = 1.8–8.5 μg/mL, and effectively kill each cell line at less than 25 μg/mL (LC50 = 10.1–24.7 μg/mL) under conventional culture conditions). Ref: M. F. Raub, et al, JACS, 1991, 113, 3178

H N

OH

295 Halichlorine Type: Quinolizidine alkaloids. C23H32ClNO3 mp 183.5–185.5 °C, [α]D = +240.7° (c = 0.54, MeOH). Source: Sponge Halichondria okadai (Japan waters). Pharm: Inhibits induction of VCAM-1 (IC50 = 7 μg/mL; drugs that block VCAM-1 may be useful for treating coronary artery diseases, angina, and noncardiovascular inflammatory diseases); antiinflammatory; antimetastatic; immunosuppressive. Ref: M. Kuramoto, et al, Tet. Lett., 1996, 37, 3867│H. Arimoto, et al, Tet. Lett., 1998, 39, 861│D. Trauner, et al, Angew. Chem., Int. Ed., 1999, 38, 3542│M. Kuramoto, et al, Mar. Drugs, 2004, 2, 39

5.2 Piperidine Alkaloids

113

H

N

O

H

O

Cl

OH

296 Isosaraine 1 Type: Quinolizidine alkaloids. C31H50N2O Amorph. solid, [α]D = −23.1° (c = 1.2, CHCl3). Source: Sponge Reniera sarai (Naples). Pharm: Insecticide. Ref: G. Cimino, et al, Tet. Lett., 1989, 30, 133│Y. Guo, et al, Tet. Lett., 1998, 39, 463

N H

9

O

2

N H

1

H

297 Saraine 1 Type: Quinolizidine alkaloids. C31H50N2O Amorphous powder, [α]D = −47.8° (c = 1.2, CHCl3). Source: Sponge Reniera sarai (Mediterranean Sea). Pharm: LD50 (mus, ipr) = 200 mg/kg. Ref: G. Cimino, et al, Bull. Soc. Chim. Belg., 1986, 95, 783

N O

H

H N

298 Aragupetrosine A Type: Xestospongins. C30H52N2O2 [α]D = −188° (CHCl3). Source: Sponge Xestospongia sp. (Okinawa). Pharm: Vasodilator. Ref: M. Kobayashi,et al, Tet. Lett., 1989, 30, 4149

114

5 Pyridines and Piperidines

O

N

H

N

H O

299 Araguspongine B Type: Xestospongins. C28H50N2O2 Source: Sponge Xestospongia sp. (Okinawa). Pharm: Vasodilator; somatostatin inhibitor. Ref: M. Kobayashi, et al, CPB, 1989, 37, 1676│T. R. Hoye, et al, JOC, 1994, 59, 6904 [erratum: 1995, 60, 4958]

N

H O

O N

H

300 (+)-Araguspongine D Xestospongin A Type: Xestospongins. C28H50N2O2 Cryst. (Et2O), mp 135–136 °C, [α]D = +6.9° (c = 0.84, CHCl3), [α]D = +10°. Source: Sponges Xestospongia exigua (Okinawa) and Xestospongia spp. Pharm: Vasodilator. Ref: M. Nakagawa, et al, Tet. Lett., 1984, 25, 3227│M. Kobayashi, et al, CPB, 1989, 37, 1676│T. R. Hoye, et al, JACS., 1994, 116, 2617│R. W. Scott, et al, JACS., 1994, 116, 8853│M. Kobayashi, et al, Heterocycles, 1998, 47, 195 7 9

H

N O

O

5

H

N

5' 9' 7'

301 Araguspongine E Xestospongin C Type: Xestospongins. C28H50N2O2 Cryst. (Et2O), mp 149–150 °C, [α]D = −2.4° (c = 0.54, CHCl3), [α]D = −1.1° (CHCl3). Source: Sponges Xestospongia sp. (Okinawa) and Xestospongia exigua (Okinawa). Pharm: Vasodilator; Calcium channel blocker; Inositol triphosphate Ins(1,4,5)P3 receptor antagonist. Ref: M. Nakagawa, et al, Tet. Lett., 1984, 25, 3227│M. Kobayashi, et al, CPB, 1989, 37, 1676│J. E. Baldwin, et al, JACS, 1998, 120, 8559│T. R. Hoye, et al, JOC, 1994, 59, 6904; 1995, 60, 4958

5.2 Piperidine Alkaloids

N

H O

O N

115

H

302 Petrosine Type: Xestospongins. C30H50N2O2 mp 215–216 °C. Source: Sponges Petrosia seriata (Papua New Guinea) and Xestospongia sp. (Okinawa). Pharm: Ichthyotoxin. Ref: J. C. Braekman, et al, Tet. Lett., 1982, 23, 4277│J. C. Braekman, et al, Bull. Soc. Chim. Belg., 1984, 93, 941; 1988, 97, 519│T. R. Hoye, et al, JACS., 1994, 116, 2617│R. W. Scott, et al, JACS., 1994, 116, 8853│R.W. Scott, et al, JOC, 1998, 63, 5001│C. H. Heathcock, et al, JOC, 1998, 63, 5013 O

N

H

N

H

O

303 Petrosine A Type: Xestospongins. C30H50N2O2 Source: Sponges Petrosia seriata and Xestospongia sp. (Okinawa). Pharm: Ichthyotoxin. Ref: J. C. Braekman, et al, Tet. Lett., 1982, 23, 4277│J. C. Braekman, et al, Bull. Soc. Chim. Belg., 1984, 93, 941; 1988, 97, 519│R. W. Scott, et al, JOC, 1998, 63, 5001│C. H. Heathcock, et al, JOC, 1998, 63, 5013 O

N

H

H

N

O

304 Petrosine B Type: Xestospongins. C30H50N2O2 [α]D = −12° (c = 0.79, CH2Cl2). Source: Sponge Petrosia seriata (Papua New Guinea). Pharm: Ichthyotoxin. Ref: J. C. Braekman, et al, Tet. Lett., 1982, 23, 4277│J. C. Braekman, et al, Bull. Soc. Chim. Belg., 1984, 93, 941; 1988, 97, 519│R. W. Scott, et al, JOC, 1998, 63, 5001│C. H. Heathcock, et al, JOC, 1998, 63, 5013

116

5 Pyridines and Piperidines

O

N

H

H

N

O

305 Xestospongin B Type: Xestospongins. C29H52N2O3 Cryst. (Et2O), mp 179–181 °C, [α]D = +7.10° (c = 0.91, CHCl3). Source: Sponge Xestospongia exigua (Okinawa). Pharm: Vasodilator. Ref: M. Nakagawa, et al, Tet. Lett., 1984, 25, 3227 HO N

H

O

O

H

N

306 Xestospongin D Araguspongine A Type: Xestospongins. C28H50N2O3 Cryst. (Et2O), mp 156–157 °C, [α]D = +18.43° (c = 1.08, CHCl3). Source: Sponge Xestospongia exigua (Okinawa). Pharm: Vasodilator. Ref: M. Nakagawa, et al, Tet. Lett., 1984, 25, 3227│M. Kobayashi, et al, CPB, 1989, 37, 1676 HO 9

N

5'

N

H

O H

5

O

6 Quinolines Isoquinolines and Quinazolines 6.1 Quinoline Alkaloids 307 Ammosamide D Type: Quinoline alkaloids. C12H9ClN4O4 Source: Marine-derived streptomycete Streptomyces variabilis (sediment, Sweetings Cay, Bahamas). Pharm: Cytotoxic (Mia-PaCa-2, modest). Ref: E. Pan, et al, Org. Lett., 2012, 14, 2390 O

NH2 Cl

N

NH2

O O

O

N H

308 4,7-Dihydroxy-8-methoxyquinoline Type: Quinoline alkaloids. C10H9NO3 Source: Soft corals Sinularia polydactyla and Sinularia microclavata. Pharm: Cardiovascular. Ref: K. Long, et al, CA, 1985, 103, 128867; 1990, 112, 118619; 1991, 115, 71358 OH

HO

N O

309 Halytulin Type: Quinoline alkaloids. C35H40N4O4 Orange foaming oil, [α]D = +7.5° (c = 2.8, MeOH). Source: Sponge Haliclona tulearensis (South Africa). Pharm: Cytotoxic (P388, IC50 = 0.025 μg/mL, A549, IC50 = 0.012 μg/mL, HT29, IC50 = 0.012 μg/mL, MEL28, IC50 = 0.025 μg/mL). Ref: Y. Kashman, et al, Tet. Lett., 1999, 40, 997 OH

OH

OH

HO

N

N N N

https://doi.org/10.1515/9783110653908-003

118

6 Quinolines Isoquinolines and Quinazolines

310 Helquinoline Type: Quinoline alkaloids. C12H15NO3 Oil. Source: Marine-derived bacterium Janibacter limosus HeL 1 (psychrophilic, cold water, culture, North Sea). Pharm: Antibacterial (Bacillus subtilis, Streptomyces viridochromogenes, and Staphylococcus aureus, moderate); antifungal. Ref: R. N. Asolkar, et al, J. Antibiot., 2004, 57, 17│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) O

N H O

OH

311 Lepadin A Type: Quinoline alkaloids. C20H33NO3 Oil, [α]D = −8.5° (c = 0.002, MeOH). Source: Marine acoel flatworm Prostheceraeus villatus (psychrophilic, cold water, waters off Bergen, Norway), ascidian Clavelina lepadiformis. Pharm: Cytotoxic (P388, ED50 = 1.2 μg/mL; MCF7, ED50 = 2.3 μg/mL; glioblastoma/astrocytoma U373, ED50 = 3.7 μg/mL; HEY, ED50 = 2.6 μg/mL; LoVo, ED50 = 1.1 μg/mL; A549, ED50 = 0.84 μg/mL). Ref: B. Steffan, Tetrahedron, 1991, 47, 8729│J. Kubanek, et al, Tet. Lett., 1995, 36, 6189│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)

H

N H H

O

OH O

312 (–)-Lepadin B Type: Quinoline alkaloids. C18H31NO [α]D = −96° (MeOH). Source: Marine acoel flatworm Prostheceraeus villatus (psychrophilic, cold water, waters off Bergen, Norway), ascidian Clavelina lepadiformis. Pharm: Cytotoxic (P388, ED50 = 2.7 μg/mL, MCF7, ED50 = 17 μg/mL, U373, ED50 = 10 μg/mL, HEY, ED50 = 15 μg/mL, LoVo, ED50 = 7.5 μg/mL, A549, ED50 = 5.2 μg/mL). Ref: J. Kubanek, et al, Tet. Lett., 1995, 36, 6189│N. Toyooka, et al, JOC, 1999, 64, 2182│N. Toyooka, et al, Tetrahedron, 1999, 55, 10673│T. Ozawa, et al, Org. Lett., 2000, 2, 2955│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)

6.1 Quinoline Alkaloids

H

119

OH

N H H

313 Marinoquinoline A 4-Methyl-3H-pyrrolo[2,3-c]quinoline Type: Quinoline alkaloids. C12H10N2 Needles (Me2CO/CHCl3/hexane). Source: Marine-derived bacterium Rapidithrix thailandica GB009. Pharm: Acetylcholinesterase inhibitor. Ref: A. Kanjana-opas, et al, Acta Cryst. E, 2006, 62, o2728│Y. Sangnoi, et al, Mar. Drugs, 2008, 6, 578

NH

N

314 22-O-(N-Me-L-valyl)-21-epiaflaquinolone B Type: Quinoline alkaloids. C32H42N2O6 Source: Fungus Aspergillus sp. XS-20090B15 Pharm: Antiviral (RSV virus, IC50 = 42 nmol/L) Ref: C. Prieto, et al, Theriogenology 2005, 63, 1 (rev)

N H

O

OH

OH

O

O

N H

O

315 2-Nonyl-4-hydroxyquinoline N-oxide Type: Quinoline alkaloids. C18H25NO2 Leaflets (EtOH), mp 148–149 °C. Source: Marine bacterium Pseudomonas sp.from lithistid sponge Homophymia sp. (Caledonia). Pharm: Cytotoxic (KB, IC50 < 2 μg/mL); antibacterial (Staphylococcus aureus, 20 mm/20 μg). Ref: V. Bultet-Poncé, et al, Mar. Biotechnol., 1999, 1, 384

120

6 Quinolines Isoquinolines and Quinazolines

OH

+

N

–

O

316 2-Nonyl-4-quinolone Type: Quinoline alkaloids. C18H25NO Cryst., mp 138.8–139.2 °C. Source: Marine bacterium Pseudomonas sp. from lithistid sponge Homophymia sp. (Caledonia). Pharm: Antimalarial (Plasmodium falciparum, ID50 = 4.8 μg/mL). Ref: V. Bultet-Poncé, et al, Mar. Biotechnol., 1999, 1, 384 O

N H

317 Penicinolone Type: Quinoline alkaloids. C14H10N2O3 Amorph. yellow powder, mp 350–352 °C. Source: Mangrove-derived fungus Penicillium sp. from mangrove Acanthus ilicifolius (bark, South China Sea). Pharm: Cytotoxic (95-D, IC50 = 0.57 μg/mL; HepG2, IC50 = 6.5 μg/mL; HeLa, KB, KBV200 and Hep2 cells, 4 IC50 > 100 μg/mL); insecticidal (Aphis gossypii, 100% mortality, 1000 ppm; Plutella xylostella, Heliothis virescens, Septoria triticiand Uromyces fabae, 100% mortality, > 1000 ppm). Ref: C. -L. Shao, et al, BoMCL, 2010, 20, 3284 H N

O

N H O OH

318 Penispirolloid A Type: Quinoline alkaloids. C21H21N5O2 Source: Marine-derived fungus Penicillium sp. Pharm: Antifoulant (Bugula neritina larvae). Ref: F. He, et al, Tet. Lett., 2012, 53, 2280

6.1 Quinoline Alkaloids

121

H N N O HN H

N

NH

O

319 2-n-Pentyl-4(1H)-quinolinol Type: Quinoline alkaloids. C14H17NO Cryst., mp 141–142 °C, mp 135 °C. Source: Marine bacterium Pseudomonas sp. Pharm: Antibacterial (Staphylococcus aureus and Vibrio sp.). Ref: S. J. Wratten, et al, Antimicrob. Agents Chemother., 1977, 11, 411 OH

N

320 4,5,8-Trihydroxy-2-quinolinecarboxylic acid Type: Quinoline alkaloids. C10H7NO5 Yellow solid, mp 295–300 °C (dec). Source: Sponge Dendrilla membranosa (Antarctic, pigment). Pharm: Antimicrobial. Ref: T. F. Molinski, et al, Tet. Lett., 1988, 29, 2137 OH

OH

OH

N OH

O

321 Tyrokeradine B (2009) Type: Quinoline alkaloids. C26H28Br2N7O7 Dark green solid. Source: An unidentified sponge (Verongida order, Kerama I., Okinawa). Pharm: Antimicrobial. Ref: H. Mukai, et al, BoMCL, 2009, 19, 1337

122

6 Quinolines Isoquinolines and Quinazolines

H N

HO

OH

Br O NH2

HO

O

N

H N

OH

Br O

HN

NH NH

322 2-Undecen-18-yl-4-quinolone Type: Quinoline alkaloids. C20H27NO Source: Marine bacterium Pseudomonas sp.from lithistid sponge Homophymia sp. (Caledonia). Pharm: Cytotoxic (KB, IC50 = 5 μg/mL); antimalarial (Plasmodium falciparum, ID50 = 3.4 μg/mL). Ref: V. Bultet-Poncé, et al, Mar. Biotechnol., 1999, 1, 384 O

N H

323 2-Undecyl-4-quinolone Type: Quinoline alkaloids. C20H29NO Cryst. (Me2CO), mp 130–132 °C. Source: Marine bacterium Pseudomonas sp. from lithistid sponge Homophymia sp. (Caledonia). Pharm: Cytotoxic (KB, IC50 > 10 μg/mL); anti-HIV-1 (ID50 = 10–3 μg/mL); antimalarial (Plasmodium falciparum, ID50 = 1 μg/mL); dihydrostreptomycin antagonist. Ref: V. Bultet-Poncé, et al, Mar. Biotechnol., 1999, 1, 384 O

N H

324 Viridicatol Type: Quinoline alkaloids. C15H11NO3 Cryst. (EtOAc), mp 280 °C. Source: Marinederived fungus Aspergillus versicolor (sediment, Sakhalin Bay, Sea of Okhotsk, Russia). Pharm: Inhibits sperm fertilizing ability, IC50 = 11.86 mmol/L; at 9.88 mmol/L, showed weak cytostatic and membranolytic effects. Ref: A. N. Yurchenko, et al, Russ. Chem. Bull., 2010, 59, 852

6.1 Quinoline Alkaloids

123

OH

OH

N H

O

325 1-Aminodiscorhabdin D Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H15N4O2S1+ Dark green solid. Source: Four sponges Tsitsikamma pedunculata, Tsitsikamma favus, Latrunculia bellae and Strongylodesma algoaensis (South Africa). Pharm: Cytotoxic (HCT116). Ref: E. M. Antunes, et al, JNP, 2004, 67, 1268 O

H N

H N

S +

N

H 2N H O

326 Batzelline B Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C11H9ClN2O2S Dark brown solid. Source: Sponge Batzella sp. (deep water, Bahamas, Caribbean Sea). Pharm: Herbicide. Ref: S. Sakemi, et al, Tet. Lett., 1989, 30, 2517│H. H. Sun, et al, JOC, 1990, 55, 4964│M. Alvarez, et al, EurJOC, 1999, 1173 S

HN O O Cl

N H

327 Batzelline C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C11H9ClN2O2 Dark brown solid. Source: Sponges Batzella sp. and Zyzzya massalis. Pharm: Herbicide. Ref: S. Sakemi, et al, Tet. Lett., 1989, 30, 2517│T. Izawa, et al, Tet. Lett., 1994, 35, 917│X. L. Tao, et al, Tetrahedron, 1994, 50, 2017│T. Izawa, et al, Tetrahedron, 1994, 50, 13593│M.-G. Dijoux, et al, BoMC, 2005, 13, 6035

124

6 Quinolines Isoquinolines and Quinazolines

O O

N

Cl NH

328 14-Bromo-7,8-didehydro-3-dihydrodiscorhabdin C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H12Br3N3O2 Green solid. Source: Four sponges Tsitsikamma pedunculata, Tsitsikamma favus, Latrunculia bellae and Strongylodesma algoaensis (South Africa). Pharm: Cytotoxic (HCT116). Ref: E. M. Antunes, et al, JNP, 2004, 67, 1268 O

H N

HN Br N Br

H

Br OH

329 14-Bromodihydrodiscorhabdin C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H14Br3N3O2 Dark green oil. Source: Sponge Tsitsikamma favus (latrunculid sponge, yield = 0.01956% dw, South Africa). Pharm: Antibacterial (Bacillus subtilis); cytotoxic. Ref: G. J. Hooper, et al, Tet. Lett., 1996, 37, 7135 O H N Br

H N

13

18

N

Br

Br OH

330 4-Bromodihydrodiscorhabdin C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H15Br3N3O21+ Source: An unidentified sponge (family latrunculidae, South Africa). Pharm: Antimicrobial. Ref: G. J. Hooper, et al, Tet. Lett., 1996, 37, 7135

6.1 Quinoline Alkaloids

O

125

H N

H N Br +

N

H Br

Br OH

331 14-Bromodiscorhabdin C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H12Br3N3O2 Dark green oil. Source: Sponge Tsitsikamma favus (latrunculid sponge, yield = 0.056% dw, South Africa). Pharm: Antibacterial (Bacillus subtilis); cytotoxic. Ref: G. J. Hooper, et al, Tet. Lett., 1996, 37, 7135 O H N Br

H N

13

18

N

Br

Br O

332 Damirone B Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C11H10N2O2 Purple solid, mp 250 °C. Source: Sponges Zyzzya fuliginosa (Fiji) and Damiria sp. Pharm: Cytotoxic (HCT116, IC50 = 0.08 μmol/L; XRS-6, IC50 = 0.02 μmol/L, HF (hypersensitivity factor) IC50 BR1/ IC50 XRS-6 = 2); topoisomerase II inhibitor (in vitro decatenrtion inhibition assay, IC90 > 500 μmol/L). Ref: D. C. Radisky, et al, JACS, 1993, 115, 1632│D. Roberts, et al, Tet. Lett., 1994, 35, 7857 O H N

O 6 5

N

333 Damirone C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C10H8N2O2 Red-brown solid. Source: Sponge Zyzzya fuliginosa (Pohnpei I., Federated States of Micronesia). Pharm: Cytotoxic (HCT116). Ref: E. W. Schmidt, et al, JNP, 1995, 58, 1861

126

6 Quinolines Isoquinolines and Quinazolines

O O

HN

NH

334 7,8-Didehydro-3-dihydrodiscorhabdin C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H13Br2N3O2 Olive-green solid. Source: Four sponges Tsitsikamma pedunculata, Tsitsikamma favus, Latrunculia bellae and Strongylodesma algoaensis (South Africa). Pharm: Cytotoxic (HCT116). Ref: E. M. Antunes, et al, JNP, 2004, 67, 1268

H N

O

H N

N Br

H

Br OH

335 3-Dihydrodiscorhabdin B Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H14BrN3O2S Dark brown-green solid (formate salt). Source: Sponge Latrunculia sp. (psychrophilic, cold water, Aleutian Is., coast of Alaska). Pharm: Anti-HCV; antimalarial; antibacterial. Ref: M. K. Na, et al, JNP, 2010, 73, 383│S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev) O HN

H N S

N Br OH

336 Dihydrodiscorhabdin C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H15Br2N3O2 Source: Sponge Latrunculia sp. (psychrophilic, cold water, Aleutian Is., coast of Alaska). Pharm: Selective antiprotozoal (in vitro, chloroquine-susceptible Plasmodium falciparum, IC50 = 170 nmol/L, CSPF, IC50 = 130 nmol/L); antimalarial negative result (murine model in vivo, high levels of toxicity were observed including weight loss, movement reduction, and dehydration). Ref: S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev)

6.1 Quinoline Alkaloids

O

127

H N

H N

N Br

Br OH

337 Discorhabdin A Prianosin A Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H14BrN3O2S Green solid (hydrochloride), [α]D24 = +248° (c = 0.19, CHCl3), [α]D = +400° (c = 0.05, MeOH) (hydrochloride). Source: Sponges Latrunculia sp. (psychrophilic, cold water, Aleutian Is., coast of Alaska) and Zyzzya fuliginosa (Fiji). Pharm: Cytotoxic (HCT116, IC50 > 50 μmol/ L; XRS-6, IC50 > 50 μmol/L, HF (hypersensitivity factor) = IC50 BR1/IC50 XRS-6 = 1); topoisomerase II inhibitor (in vitro decatenrtion inhibition assay, IC90 > 500 μmol/L); selective anti-protozoal (in vitro, chloroquine-susceptible Plasmodium falciparum, IC50 = 53 nmol/L, CRPF, IC50 = 53 nmol/L); antimalarial negative result (murine model in vivo, high levels of toxicity were observed including weight loss, movement reduction, and dehydration). Ref: J. Kobayashi, et al, Tet. Lett., 1987, 28, 4939│J. Cheng, et al, JOC, 1988, 53, 4621│D. C. Radisky, et al, JACS, 1993, 115, 1632│S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev) O HN

H N S

N Br O

338 Discorhabdin B Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H12BrN3O2S Green solid (hydrochloride), mp > 360 °C (hydrochloride), [α]D = +400° (c = 0.2, MeOH) (hydrochloride). Source: Sponges Latrunculia wellingtonensis and Latrunculia fiordensis. Pharm: Cytotoxic (murine and hmn tumor cell lines, IC50 = 0.1 μmol/ L). Ref: N. B. Perry, et al, Tetrahedron, 1988, 44, 1727│T. Grkovic, et al, JNP, 2010, 73, 1686

128

6 Quinolines Isoquinolines and Quinazolines

O

H N

H N

8S

S

7

6S

N

16 17

5 4

Br O

339 Discorhabdin C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H13Br2N3O2 mp > 360 °C (HCl), [α]D = 0° (HCl). Source: Sponge Latrunculia cf. bocagei (psychrophilic, cold water, New Zealand), sponge Latrunculia apicalis (psychrophilic, cold water, Antarctic). Pharm: Cytotoxic (BSC, P388); cytotoxic (L1210, ED50 < 100 ng/mL); selective anti-protozoal (in vitro, chloroquine-susceptible Plasmodium falciparum, IC50 = 2800 nmol/L, CRPF, IC50 = 2000 nmol/L); antimicrobial (6 mm paper disc assay, 30 μg of test compound, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans, IZD = 2 mm, 8 mm, 0 mm, 0 mm, respectively); LD50 (mus, ipr) = 2 mg/kg. Ref: N. B. Perry, et al, J. Org. Chem. 1986, 51, 5476│N. B. Perry, et al, Tetrahedron, 1988, 44, 1727│Y. Kita, et al, JACS, 1992, 114, 2175│B. R. Copp, et al, JOC, 1994.59, 8233│T. Izawa, et al, Tet. Lett., 1994, 35, 917│X. L. Tao, et al, Tetrahedron, 1994, 50, 2017│T. Izawa, et al, Tetrahedron, 1994, 50, 13593│A. Yang, et al, JNP, 1995, 58, 1596│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)│S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev) O HN

H N

N Br

Br O

340 (+)-(2S,6R,8S)-Discorhabdin D Prianosin D Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H14N3O2S1+ Green solid, mp 300 °C, [α]D26 = +344° (c = 0.01, MeOH). Source: Sponges Latrunculia brevis, Prianos melanos, Latrunculia wellingtonensis, Latrunculia trivetricillata and Sceptrella sp. Pharm: Cytotoxic (murine and hmn tumor cell lines, IC50 = 1–15 μmol/L); antimicrobial action; induces Ca2+ release from sarcoplasmic reticulum. Ref: N. B. Perry, et al, JOC, 1988, 53, 4127│T. Grkovic, et al, JNP, 2010, 73, 1686

6.1 Quinoline Alkaloids

O

129

H N

HN

S

N

+

H O

341 Discorhabdin E Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H14BrN3O2 Red solid (trifluoroacetate). Source: Sponges Latrunculia sp. (New Zealand) and Latrunculia sp. (psychrophilic, cold water, Aleutian Is., coast of Alaska). Pharm: Cytotoxic (BSC, P388); antimicrobial (6 mm paper disc assay, 30 μg of test compound, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans, IZD = 6 mm, 4 mm, 0 mm, 1 mm, respectively). Ref: N. B. Perry, et al, Tetrahedron, 1988, 44, 1727│B. R. Copp, et al, JOC, 1994.59, 8233│S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev) O

H N

HN

N Br O

342 Discorhabdin G‡ Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H15BrN3O21+ Green pigment (trifluoroacetate), [α]D = +27.0° (c = 0.063, MeOH). Source: Sponge Latrunculia apicalis (Antarctic). Pharm: Antifeedant (for major Antarctic sponge predator); antimicrobial (inhibits growth in two common water column microorganisms isolated from the surrounding water). Ref: A. Yang, et al, JNP, 1995, 58, 1596│E. V. Sadanandan, et al, JOC, 1995, 60, 1800│F. Yamada, et al, Heterocycles, 1995, 41, 1905│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)

H N

O

H N

N Br O

130

6 Quinolines Isoquinolines and Quinazolines

343 (+)-Discorhabdin I Discorhabdin G‡ Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H13N3O2S Green solid (trifluoroacetate salt), [α]D = +540° (c = 0.05, MeOH) (trifluoroacetate salt). Source: Sponge Latrunculia brevis. Pharm: Cytotoxic (14 tumor cell lines with strong activities, HT29, GI50 = 0.35 μmol/L). Ref: F. Reyes, et al, JNP, 2004, 67, 463 O

H N

H N

S 5

N

16

4

17

O

344 (–)-Discorhabdin L Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H14N3O3S1+ Green solid (trifluoroacetate salt), mp > 250 °C, [α]D25 = −333° (c = 0.09, MeOH). Source: Sponges Sceptrella sp. (Korea waters) and Latrunculia brevis. Pharm: Cytotoxic (murine and hmn tumor cell lines, IC50 = 1–15 μmol/L); cytotoxic (14 tumor cell lines with strong activities, HT29, GI50 = 0.12 μmol/L). Ref: F. Reyes, et al, JNP, 2004, 67, 463│T. Grkovic, et al, JNP, 2010, 73, 1686 O H N HN

S

N

+

H

HO H O

345 (–)-(1R,2S,6R,8S)-Discorhabdin N Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C20H17N4O4S1+ Red-brown solid; trifluoroacetate salt, dark green oil; [α]D20 = −160°, [α]578 = −260°, [α]546 = −52° (c = 0.05, MeOH). Source: Sponges Latrunculia bellae and Latrunculia wellingtonensis. Pharm: Cytotoxic (murine and hmn tumor cell lines, IC50 = 1–15 μmol/L). Ref: E. M. Antunes, et al, JNP, 2004, 67, 1268│T. Grkovic, et al, JNP, 2010, 73, 1686

6.1 Quinoline Alkaloids

131

O H N

H N

S N

+

H

HN H O

HO O

346 Discorhabdin P N13-Methyl-discorhabdin C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C19H15N3O2Br2 mp > 360 °C (blacked at 162 °C). Source: Sponge Batzella sp. (deep water, Bahamas, Caribbean Sea). Pharm: Cytotoxic (P388, IC50 = 0.025 μg/mL; A549, IC50 = 0.41 μg/mL); inhibits calcineurin (CaN) (IC50 = 0.55 μg/mL); peptidase CPP32 inhibitor (IC50 = 0.37 μg/mL). Ref: S. P. Gunasekera, et al, JNP, 1999, 62, 173 O N

H N

13

N Br

Br O

347 (−)-(6S,8R)-Discorhabdin Q Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H10BrN3O2S Orange solid, [α]D = −452.4° (c = 0.004, CHCl3), [α]D = −904° (c = 0.0125, MeOH). Source: Sponges Latrunculia purpurea and Zyzzya spp. (at least three species) Pharm: Cytotoxic (NCI 60 cell lines, GI50 = 0.5 μg/mL). Ref: M. -G. Dijoux, et al, JNP, 1999, 62, 636 O N

H N S 5

N

16

4 17

Br O

132

6 Quinolines Isoquinolines and Quinazolines

348 Discorhabdin R Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H13N3O3S Green solid, [α]D20 = +161° (c = 0.1, MeOH). Source: Sponges Latrunculia sp. (psychrophilic, cold water, Prydz Bay, Antarctica) and Negombata sp. Pharm: Antibacterial (gram-positive: Staphylococcus aureus, Micrococcus luteus; gram-negative: Serratia marcescens, Escherichia coli). Ref: J. Ford, et al, JNP, 2000, 63, 1527│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)│S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev) O H N

H N S

N

O

O

349 Discorhabdin S Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C20H16BrN3O2S Dark orange solid. Source: Sponge Batzella sp. Pharm: Cytotoxic (PANC1, P388, and A549). Ref: S. P. Gunasekera, et al, JNP, 2003, 66, 1615│T. Grkovic, et al, JNP, 2010, 73, 1686 O N

H N 8 7

S N

16 17

Br O

350 Discorhabdin T Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C20H14BrN3O2S Dark orange solid. Source: Sponge Batzella sp. Pharm: Cytotoxic (PANC1, P388, and A549). Ref: S. P. Gunasekera, et al, JNP, 2003, 66, 1615│T. Grkovic, et al, JNP, 2010, 73, 1686 O N

H N 8 7

S N

16 17

Br O

6.1 Quinoline Alkaloids

133

351 Discorhabdin U Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C20H16BrN3O2S Dark orange solid. Source: Sponge Batzella sp. Pharm: Cytotoxic (murine and hmn tumor cell lines, IC50 = 0.1 μmol/L). Ref: S. P. Gunasekera, et al, JNP, 2003, 66, 1615│T. Grkovic, et al, JNP, 2010, 73, 1686 O

H N

N

8 7

S N

16 17

Br O

352 Discorhabdin V Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H17BrN3O21+ Dark green solid (trifluoroacetate salt). Source: Four sponges Tsitsikamma pedunculata, Tsitsikamma favus, Latrunculia bellae and Strongylodesma algoaensis (South Africa). Pharm: Cytotoxic (HCT116). Ref: E. M. Antunes, et al, JNP, 2004, 67, 1268 O

H N

H N 14

N

+

1

Br OH

353 (S,S)-Discorhabdin W Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C36H22Br2N6O4S2 [α]D = −260° (c = 0.05, MeOH) Source: Sponge Latrunculia sp. (New Zealand). Pharm: Cytotoxic (P388). Ref: G. Lang, et al, JNP, 2005, 68, 1796│T. Grkovic, et al, JOC, 2008, 73, 9133 O H N

H N

H N

S 17

H N

S N

N

16

O

Br

Br O

O

134

6 Quinolines Isoquinolines and Quinazolines

354 (R,R)-Discorhabdin W Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C36H22Br2N6O4S2 [α]D20 = +220° (c = 0.05, MeOH). Source: Sponges Latrunculia fiordensis and Latrunculia sp. Pharm: Cytotoxic (murine and hmn tumor cell lines, IC50 = 0.1 μmol/L). Ref: G. Lang, et al, JNP, 2005, 68, 1796│T. Grkovic, et al, JOC, 2008, 73, 9133│T. Grkovic, et al, JNP, 2010, 73, 1686 O H N

H N

H N

S 17

H N

S N

N

16

O

Br

Br O

O

355 Discorhabdin Y Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H16BrN3O2 Purple solid (formate salt), [α]D25 = +20° (c = 0.01, MeOH). Source: Sponge Latrunculia sp. (psychrophilic, cold water, Aleutian Is., coast of Alaska). Pharm: Anti-HCV; antimalarial; antibacterial. Ref: M. K. Na, et al, JNP, 2010, 73, 383│S. Abbas, Mar. Drugs, 2011, 9, 2423 (rev) O H N

H N

N Br O

356 (−)-Discorhabdin Z Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H18N3O51+ Dark purple solid, [α]D25 = −188° (c = 0.009, MeOH). Source: Sponge Sceptrella sp. (Korea waters). Pharm: Antibacterial (Micrococcus luteus, MIC = 50 μg/mL, MMOA: sortase A inhibitor). Ref: J. E. Jeon, et al, JNP, 2010, 73, 258 O

H N

H N

OH

HO

O N

+

H OH

6.1 Quinoline Alkaloids

135

357 Epinardine A Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H18N3O31+ Green powder. Source: An unidentified sponge (deep water, spinach-green coloured, South Indian Ocean). Pharm: Cytotoxic (in vitro, doxorubicin-resistant L1210/Dx cells, IC50 = (6.8 ± 0.5)μg/mL; L1210 cells, IC50 = (1.7 ± 0.2)μg/mL, resistant index RI = 4; control Doxorubicin, L1210/Dx cells, IC50 = (0.711 ± 0.064)μg/mL; L1210 cells, IC50 = (0.0297 ± 0.004)μg/mL, RI = 24). Ref: M. D‘Ambrosio, et al, Tetrahedron, 1996, 52, 8899 O

H N

H N

N

+

HO OH

358 Epinardine C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H15Br2N3O2 Green powder. Source: An unidentified sponge (deep water, spinach-green coloured, South Indian Ocean). Pharm: Cytotoxic (in vitro, doxorubicin-resistant L1210/Dx cells, IC50 = (0.358 ± 0.02) μg/mL; L1210 cells, IC50 = (0.324 ± 0.004)μg/mL, resistant index RI = 1; control Doxorubicin, L1210/Dx cells, IC50 = (0.711 ± 0.064)μg/mL; L1210 cells, IC50 = (0.0297 ± 0.004)μg/mL, RI = 24). Ref: M. D‘Ambrosio, et al, Tetrahedron, 1996, 52, 8899 O

H N

H N

N Br

Br OH

359 Isobatzelline A Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C12H12ClN3OS Brown solid. Source: Sponge Batzella sp. (deep water, Caribbean Sea). Pharm: Cytotoxic; antifungal. Ref: S. Sakemi, et al, Tet. Lett., 1989, 30, 2517│H. H. Sun, et al, JOC, 1990, 55, 4964│M. Alvarez, et al, EurJOC, 1999, 1173 N S

Cl NH2

N O

136

6 Quinolines Isoquinolines and Quinazolines

360 Isobatzelline B Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C12H13N3OS Red-brown solid. Source: Sponge Batzella sp. (deep water, Caribbean Sea). Pharm: Cytotoxic; antifungal. Ref: S. Sakemi, et al, Tet. Lett., 1989, 30, 2517│H. H. Sun, et al, JOC, 1990, 55, 4964│M. Iwao, et al, Tetrahedron, 1998, 54, 8999│M. Alvarez, et al, Tet. Lett., 1998, 39, 679│G. A. Kraus et al, JOC, 1998, 63, 9846│M. Alvarez, et al, EurJOC, 1999, 1173 N S NH2

N O

361 Isobatzelline C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C11H10ClN3O Green-brown or red solid. Source: Sponge Batzella sp. Pharm: Cytotoxic (HeLa-S3, IC50 = 5.65 μg/mL). Ref: S. Sakemi, et al, Tet. Lett., 1989, 30, 2517│T. Izawa, et al, Tet. Lett., 1994, 35, 917│X. L. Tao, et al, Tetrahedron, 1994, 50, 2017│T. Izawa, et al, Tetrahedron, 1994, 50, 13593 N Cl N

H 2N O

362 Isobatzelline D Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C12H10ClN3OS Red–brown solid. Source: Sponge Batzella sp. Pharm: Cytotoxic; antifungal (moderate). Ref: H. H. Sun, et al, JOC, 1990, 55, 4964 O NH2

N S

Cl 3

N

363 Makaluvamine A Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C11H12N3O1+ Green solid (trifluoroacetate). Source: Sponges Zyzzya fuliginosa (Fiji) and Zyzzya massalis. Pharm: Cytotoxic

6.1 Quinoline Alkaloids

137

(HCT116, IC50 = 1.3 μmol/L; XRS-6, IC50 = 0.41 μmol/L, HF (hypersensitivity factor) = IC50 BR1/IC50 XRS-6 = 9, mechanism of action involving DNA double-stranded breakage, an activity characteristic of topoisomerase I1 inhibitors); topoisomerase II inhibitor (in vitro decatenrtion inhibition assay, IC90 = 41 μmol/L); antineoplastic (in vivo dose 0.5 mg/kg, hmn ovarian carcinoma OVCAR-3, T/C = 62%; P388 murine leukemia, only marginal life extension). Ref: D. C. Radisky, et al, JACS, 1993, 115, 1632│T. Izawa, et al, Tet. Lett., 1994, 35, 917│X. L. Tao, et al, Tetrahedron, 1994, 50, 2017 O NH2

N

N

+

H

364 Makaluvamine B Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C11H10N3O1+ Red solid (trifluoroacetate). Source: Sponges Zyzzya fuliginosa (Fiji) and Zyzzya massalis. Pharm: Cytotoxic (HCT116, IC50 > 50 μmol/L; XRS-6, IC50 = 13.49 μmol/L, HF (hypersensitivity factor) = IC50 BR1/IC50 XRS-6 = 1); topoisomerase II inhibitor (in vitro decatenrtion inhibition assay, IC90 > 500 μmol/L). Ref: D. C. Radisky, et al, JACS, 1993, 115, 1632│T. Izawa, et al, Tet. Lett., 1994, 35, 917│X. L. Tao, et al, Tetrahedron, 1994, 50, 2017 O NH2

N

N

+

H

365 Makaluvamine C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C11H12N3O1+ Green solid (trifluoroacetate). Source: Sponges Zyzzya fuliginosa (Fiji) and Zyzzya massalis. Pharm: Cytotoxic (HCT116, IC50 = 36.2 μmol/L; XRS-6, IC50 = 5.4 μmol/L, HF (hypersensitivity factor) = IC50 BR1/IC50 XRS-6 = 4, mechanism of action involving DNA double-stranded breakage, an activity characteristic of topoisomerase I1 inhibitors); topoisomerase II inhibitor (in vitro decatenrtion inhibition assay, IC90 = 420 μmol/L); antineoplastic (in vivo dose 5.0 mg/kg, hmn ovarian carcinoma OVCAR-3, T/C = 48%; P388 murine leukemia, only marginal life extension). Ref: D. C. Radisky, et al, JACS, 1993, 115, 1632│T. Izawa, et al, Tet. Lett., 1994, 35, 917│X. L. Tao, et al, Tetrahedron, 1994, 50, 2017

138

6 Quinolines Isoquinolines and Quinazolines

O NH2

HN

N

+

366 Makaluvamine D Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H18N3O21+ Brown solid (trifluoroacetate). Source: Sponges Zyzzya fuliginosa (Fiji) and Zyzzya massalis. Pharm: Cytotoxic (HCT116, IC50 = 17.1 μmol/L; XRS-6, IC50 = 14.0 μmol/L, HF (hypersensitivity factor) = IC50 BR1/IC50 XRS-6 = 3, mechanism of action involving DNA double-stranded breakage, an activity characteristic of topoisomerase I1 inhibitors); topoisomerase II inhibitor (in vitro decatenrtion inhibition assay, IC90 = 320 μmol/L). Ref: D. C. Radisky, et al, JACS, 1993, 115, 1632│T. Izawa, et al, Tet. Lett., 1994, 35, 917│X. L. Tao, et al, Tetrahedron, 1994, 50, 2017 O

H N

H N

N

+

H

OH

367 Makaluvamine E Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C19H18N3O21+ Green solid (trifluoroacetate). Source: Sponges Zyzzya fuliginosa (Fiji) and Zyzzya massalis. Pharm: Cytotoxic (HCT116, IC50 = 1.2 μmol/L; XRS-6, IC50 = 1.7 μmol/L, HF (hypersensitivity factor) = IC50 BR1/IC50 XRS-6 = 4, mechanism of action involving DNA doublestranded breakage, an activity characteristic of topoisomerase I1 inhibitors); topoisomerase II inhibitor (in vitro decatenrtion inhibition assay, IC90 = 310 μmol/L). Ref: D. C. Radisky, et al, JACS, 1993, 115, 1632│T. Izawa, et al, Tet. Lett., 1994, 35, 917│X. L. Tao, et al, Tetrahedron, 1994, 50, 2017 O N

H N

+

N H

OH

368 Makaluvamine F Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H15BrN3O2S1+ Orange solid (trifluoroacetate), [α]D = −475.80° (c = 0.0248, MeOH). Source: Sponge Zyzzya fuliginosa (Fiji). Pharm: Cytotoxic (HCT116, IC50 = 0.17 μmol/L; XRS-6, IC50 = 0.08 μmol/L, HF

6.1 Quinoline Alkaloids

139

(hypersensitivity factor) = IC50 BR1/IC50 XRS-6 = 6, mechanism of action involving DNA double-stranded breakage, an activity characteristic of topoisomerase I1 inhibitors); topoisomerase II inhibitor (IC90 = 25 μmol/L). Ref: D. C. Radisky, et al, JACS, 1993, 115, 1632 O

H N

HN

S N

+

Br

H OH

369 Makaluvamine G Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C20H18N3O21+ Green-black powder, mp 250 °C. Source: Sponges Histodermella sp. (Indonesia) and Zyzzya cf. fuliginosa (Vanuatu). Pharm: Cytotoxic; topoisomerase I inhibitor (in vitro, moderate). Ref: J. R. Carney, et al, Tetrahedron, 1993, 49, 8483│A. Casapullo, et al, JNP, 2001, 64, 1354 O

H N

N

9

1

3

4

5

+

N

OH

370 Makaluvamine H Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C12H14N3O1+ Red-brown solid (trifluoroacetate). Source: Sponge Zyzzya fuliginosa (Pohnpei I., Federated States of Micronesia). Pharm: Cytotoxic (HCT116). Ref: E. W. Schmidt, et al, JNP, 1995, 58, 1861 O NH2

N

+

N

371 Makaluvamine I Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C10H10N3O1+ Green solid (trifluoroacetate). Source: Sponges Zyzzya fuliginosa (Pohnpei I., Federated States of Micronesia) and Zyzzya spp. Pharm: Cytotoxic (HCT116); cytotoxic (topoisomerase II sensitive CHO cell-line XVS); topoisomerase II inhibitor (in vitro). Ref: E. W. Schmidt, et al, JNP, 1995, 58, 1861

140

6 Quinolines Isoquinolines and Quinazolines

O NH2

HN

NH

+

372 Makaluvamine J Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C19H20N3O21+ Red-brown solid (trifluoroacetate). Source: Sponges Zyzzya fuliginosa (Pohnpei I., Federated States of Micronesia) and Zyzzya cf. fuliginosa (Vanuatu). Pharm: Cytotoxic (HCT116). Ref: E. W. Schmidt, et al, JNP, 1995, 58, 1861│A. Casapullo, et al, JNP, 2001, 64, 1354 O

H N

HN

N

+

OH

373 Makaluvamine K Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C19H20N3O21+ Red-brown solid (trifluoroacetate). Source: Sponges Zyzzya fuliginosa (Pohnpei I., Federated States of Micronesia), Zyzzya cf. fuliginosa (Vanuatu) and Zyzzya spp. Pharm: Cytotoxic (HCT116); cytotoxic (topoisomerase II sensitive CHO cell-line XVS); topoisomerase II inhibitor (in vitro). Ref: E. W. Schmidt, et al, JNP, 1995, 58, 1861│A. Casapullo, et al, JNP, 2001, 64, 1354 O

H N

N

NH

+

OH

374 Makaluvamine L Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C19H18N3O21+ Green solid (trifluoroacetate). Source: Sponges Zyzzya fuliginosa (Pohnpei I., Federated States of Micronesia) and Zyzzya cf. fuliginosa (Vanuatu). Pharm: Cytotoxic (HCT116). Ref: E. W. Schmidt, et al, JNP, 1995, 58, 1861│A. Casapullo, et al, JNP, 2001, 64, 1354

6.1 Quinoline Alkaloids

O

H N

HN

N

141

+

OH

375 Makaluvamine M Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H16N3O21+ Green solid (trifluoroacetate). Source: Sponge Zyzzya fuliginosa (Pohnpei I., Federated States of Micronesia). Pharm: Cytotoxic (HCT116). Ref: E. W. Schmidt, et al, JNP, 1995, 58, 1861 O

H N

HN

+

N

H

OH

376 Makaluvamine N Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C10H9BrN3O1+ Reddish-brown solid. Source: Sponge Zyzzya fuliginosa (Philippines). Pharm: Topoisomerase II inhibitor. Ref: D. A. Venables, et al, JNP, 1997, 60, 408 O H N

NH2 Br +

N

H

377 Makaluvamine P Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C20H22N3O21+ Violet solid. Source: Sponge Zyzzya cf. fuliginosa (Vanuatu). Pharm: Cytotoxic (KB, 3.2 μg/mL InRt = 64%); antioxidant (high inhibition of xanthine oxidase (an important biological source of superoxide radicals), IC50 = 16.5 μmol/L). Ref: A. Casapullo, et al, JNP, 2001, 64, 1354 O N

H N

+

N

OH

142

6 Quinolines Isoquinolines and Quinazolines

378 Makaluvone Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C11H10BrN2O2 Grey solid. Source: Sponge Zyzzya fuliginosa (Fiji). Pharm: Cytotoxic (HCT116, IC50 > 50 μmol/L; XRS-6, IC50 > 50 μmol/L, HF (hypersensitivity factor) = IC50BR1/IC50 XRS-6 = 1); topoisomerase II inhibitor (in vitro decatenrtion inhibition assay, IC90 > 500 μmol/L). Ref: D. C. Radisky, et al, JACS, 1993, 115, 1632│M.-G. Dijoux, et al, BoMC, 2005, 13, 6035 O N

O

Br NH

379 Prianosin B Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H12BrN3O2S Red cryst., mp 250–251 °C (dec), [α]D30 = +360° (c = 0.1, CHCl3). Source: Sponge Prianos melanos. Pharm: Cytotoxic (L1210). Ref: J. Cheng, et al, JOC, 1988, 53, 4621 O

H N

H N

S 5

N

16 17

4

Br O

380 N-1-β-D-Ribofuranosyldamirone C Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C15H18N2O6 Source: Sponge Strongylodesma aliwaliensis (South Africa). Pharm: Cytotoxic (esophageal cancer cell lines WHCO1, WHCO6, and KYSE30, IC50 = 1.6–85.5 μmol/L). Ref: R. A. Keyzers, et al, Tet. Lett., 2004, 45, 9415│C. E. Whibley, Ann. N. Y. Acad. Sci., 2005, 1056, 405 NH

HO O

N

O O

OH OH

6.1 Quinoline Alkaloids

143

381 N-1-β-D-Ribofuranosylmakaluvamine I Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C15H21N3O5 Source: Sponge Strongylodesma aliwaliensis (South Africa). Pharm: Cytotoxic (esophageal cancer cell lines WHCO1, WHCO6, and KYSE30, IC50 = 1.6–85.5 μmol/L). Ref: R. A. Keyzers, et al, Tet. Lett., 2004, 45, 9415│C. E. Whibley, Ann. N. Y. Acad. Sci., 2005, 1056, 405 NH

HO O

N

NH2 O

OH OH

382 1-Thiomethyldiscorhabdin I Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C19H15N3O2S2 [α]D = +640° (c = 0.5, MeOH) (trifluoroacetate salt). Source: Sponge Latrunculia wellingtonensis [Syn. Biannulata wellingtonesis] (Wellington, New Zealand). Pharm: Cytotoxic. Ref: T. Grkovic, et al, Tetrahedron, 2009, 65, 6335 O H N

H N

S

N S O

383 Tsitsikammamine A Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C18H13N3O2 Dark green oil. Source: Sponge Tsitsikamma favus (latrunculid sponge, yield = 0.04% dw, South Africa), an unidentified sponge. Pharm: Antibacterial (Bacillus subtilis); cytotoxic. Ref: G. J. Hooper, et al, Tet. Lett., 1996, 37, 7135 O H N

H N

N

OH

144

6 Quinolines Isoquinolines and Quinazolines

384 Tsitsikammamine B Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C19H15N3O2 Dark green oil. Source: Sponge Tsitsikamma favus (latrunculid sponge, yield = 0.045% dw, South Africa), an unidentified sponge. Pharm: Antibacterial (Bacillus subtilis); cytotoxic. Ref: G. J. Hooper, et al, Tet. Lett., 1996, 37, 7135 O H N

N

N

OH

385 Veiutamine Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C17H16N3O21+ Green solid (trifluoroacetate). Source: Sponge Zyzzya fuliginosa (Fiji). Pharm: Cytotoxic (HCT116, IC50 = 0.3 μg/mL). Ref: D. A. Venables, et al, Tet. Lett., 1997, 38, 721│Y. Moro-oka, et al, Tet. Lett., 1999, 40, 1713 O NH2

HN

+

N

H

OH

386 Wakayin Type: Pyrrolo[4,3,2-de]quinoline alkaloids. C20H14N4O Source: Ascidian Clavelina sp. Pharm: Cytotoxic (HCT116, IC50 = 0.5 μg/mL); antibacterial (Bacillus subtilis, MIC = 0.3 μg/mL); topoisomerase inhibitor. Ref: B. R. Copp, et al, JOC, 1991, 56, 4596 O H N

H N

N N H

6.1 Quinoline Alkaloids

145

387 9-Aminoisoascididemnin Type: Pyrido[2,3,4-kl]acridines. C18H10N4O Amorph. yellow solid (natural). Source: Sponge Biemna fortis. Pharm: Neuronal differentiation inducer. Ref: Aoki, S. et al, BoMC, 2003, 11, 1969-1 N O NH2

N

9

N

388 Amphimedine Type: Pyrido[2,3,4-kl]acridines. C19H11N3O2 Yellow solid, mp 360 °C. Source: Sponges Xestospongia cf. carbonaria (Urukthapel I., Palau, Oceania) and Amphimedon sp. (depth of 3 m, Pacific, Guam). Pharm: Zebrafish phenotype-based assay (caused a phenotype in zebrafish embryos at 30 μmol/L); cytotoxic; topoisomerase II inhibitor. Ref: F. J. Schmitz, et al,. JACS, 1983, 105, 4835│X. Wei, et al, Mar. Drugs, 2010, 8, 1769

N O N

N O

389 Arnoamine A Type: Pyrido[2,3,4-kl]acridines. C17H10N2O Yellow glass. Source: Ascidian Cystodytes sp. (Arno Atoll, Micronesia). Pharm: Cytotoxic (MCF7, GI50 = 0.3 μg/mL, A549, GI50 = 2.0 μg/mL, HT29, GI50 = 4.0 μg/mL); topoisomerase II inhibitor (iInhibits catalytic activity of topoisomerase II at concentration higher than 90 μmol/L). Ref: A. Plubrukarn, et al, JOC, 1998, 63, 1657│E. Delfourne, et al, JOC, 2000, 65, 5476 N HO N

390 Arnoamine B Type: Pyrido[2,3,4-kl]acridines. C18H12N2O Yellow glass. Source: Ascidian Cystodytes sp. (Arno Atoll, Micronesia). Pharm: Cytotoxic (MCF7, GI50 = 5.0 μg/mL, A549,

146

6 Quinolines Isoquinolines and Quinazolines

GI50 = 2.0 μg/mL, HT29, GI50 = 3.0 μg/mL); topoisomerase II inhibitor (inhibits catalytic activity of topoisomerase II at concentration higher than 90 μmol/L). Ref: A. Plubrukarn, et al, JOC, 1998, 63, 1657│E. Delfourne, et al, JOC, 2000, 65, 5476 N O

N

391 Arnoamine C Type: Pyrido[2,3,4-kl]acridines. C22H17N3O2 Source: Ascidian Cystodytes violatinctus (Solomon Is.). Pharm: Cytotoxic (panel of hmn tumours HTCLs, modest). Ref: N. Bontemps, et al, JNP, 2013, 76, 1801 N OH

N O N H

392 Arnoamine D Type: Pyrido[2,3,4-kl]acridines. C22H17N3O2 Source: Ascidian Cystodytes violatinctus (Solomon Is.). Pharm: Cytotoxic (panel of hmn tumours HTCLs, modest). Ref: N. Bontemps, et al, JNP, 2013, 76, 1801 N OH

N O N H

393 Ascididemin Leptoclinidinone Type: Pyrido[2,3,4-kl]acridines. C18H9N3O Yellow solid, mp 300 °C. Source: Ascidians Polysyncraton echinatum (Farquharson Reef, Queensland, Australia), Didemnum sp. (Okinawa), Cystodytes dellechiajei, Didemnum rubeum and Eudistoma

6.1 Quinoline Alkaloids

147

sp. (Seychelles). Pharm: Antitrypanosomal (Trypanosoma brucei brucei); cytotoxic (IC50 = 30–77 nmol/L, while exhibiting only mild cytotoxicity for control mammalian cell-line); cytotoxic (P388, IC50 = 0.35 μmol/L; A549, IC50 = 0.02 μmol/L; HT29, IC50 = 0.35 μmol/L; SK-MEL-28, IC50 = 0.004 μmol/L); antibacterial (Escherichia coli and Micrococcus luteus, most active pyridoacridine alkaloids); antineoplastic (potent); Ca2+ release agent; DNA intercalator and cleavage agent. Ref: J. Kobayashi, et al, Tet. Lett., 1988, 29, 1177│C. J. Moody, et al, Tetrahedron, 1992, 48, 3589│M. Álvarez, et al, EurJOC, 2000, 849│M. Álvarez, et al, Tetrahedron, 2000, 56, 3703│Y. Feng, et al, Tet. Lett., 2010, 51, 2477 N N

N O

394 Biemnadin Type: Pyrido[2,3,4-kl]acridines. C27H19N5O Yellow cryst. (hydrochloride), mp 300 °C (hydrochloride). Source: Sponges Ecionemia geodides (Moorina Bay, Tasmania, Australia), Biemna sp. (Okinawa) and Biemna fortis. Pharm: Cytotoxic (invasive bladder cancer TSU-Pr1, 10 μmol/L, inactive, control Doxorubicin, 1 μmol/L, InRt = 96%; superficial bladder cancer 5637, 10 μmol/L, InRt = 22%, Doxorubicin, 1 μmol/L, InRt = 99%); cytotoxic (KB, IC50 = 1.73 μg/mL; L1210, IC50 = 4.29 μg/mL); neuronal differentiation inducer. Ref: H. He, et al, JOC, 1991, 56, 5369│C.-M. Zeng, et al, Tetrahedron, 1993, 49, 8337│S. Aoki, et al, BoMC, 2003, 11, 1969│E. C. Barnes, et al, Tetrahedron, 2010, 66, 283 N

N

N H

H N

N

O

395 2-Bromoleptoclinidinone Type: Pyrido[2,3,4-kl]acridines. C18H8BrN3O Yellow powder (CHCl3/MeOH), mp 300 °C. Source: Ascidian Leptoclinides sp. Pharm: Cytotoxic (lymphocytic leukaemia cells in vitro); protein phosphatase inhibitor. Ref: F. S. De Guzman, et al, Tet. Lett., 1989, 30, 1069

148

6 Quinolines Isoquinolines and Quinazolines

N N

N

Br

O

396 Cyclodercitine Type: Pyrido[2,3,4-kl]acridines. C19H14N3S1+ Blue powder (chloride), mp 298 °C (chloride). Source: Sponge Dercitus sp. (deep water). Pharm: Cytotoxic (P388). Ref: G. P. Gunawardana, et al, JOC, 1992, 57, 1523 +

N N S

N 10

9

397 Cystodamine 11-Hydroxyascididemin Type: Pyrido[2,3,4-kl]acridines. C18H9N3O2 Yellow amorph. solid, mp 250 °C. Source: Ascidians Leptoclinides sp. and Cystodytes dellechiajei (Mediterranean Sea). Pharm: Cytotoxic (CEM, IC50 = 1.0 μg/mL). Ref: N. Bontemps, et al, Tet. Lett., 1994, 35, 7023│Y. Kitahara, et al, Tetrahedron, 1998, 54, 8421│Delfourne, E. et al, Tet. Lett., 2000, 41, 3863 N N 9

8

10

11

2

N OH

O

398 Cystodytin A Type: Pyrido[2,3,4-kl]acridines. C22H19N3O2 Yellow cryst., mp 181–183 °C. Source: Ascidians Cystodytes sp. (Fiji) and Cystodytes dellechiajei. Pharm: Topoisomerase II inhibitor; Ca2+ release agent. Ref: J. Kobayashi, et al, JOC, 1988, 53, 1800│L. A. McDonald, et al, JMC, 1994, 37, 3819

6.1 Quinoline Alkaloids

149

N O

N

H N O

399 Cystodytin B Type: Pyrido[2,3,4-kl]acridines. C22H19N3O2 Source: Ascidian Cystodytes dellechiajei. Pharm: Calcium release activity. Ref: J. Kobayashi, et al, JOC, 1988, 53, 1800 N O

N

H N O

400 Cystodytin J Type: Pyrido[2,3,4-kl]acridines. C19H15N3O2 Yellow solid. Source: Ascidian Cystodytes sp. (Fiji). Pharm: Cytotoxic (HCT, IC50 = 1.6 μmol/L, control Etoposide, IC50 = 2.5 μmol/L; XRS-6, IC50 = 135.6 μmol/L, Etoposide, IC50 = 0.14 μmol/L, dosedependent inhibition of proliferation); differential cytotoxicity (ratio BR1 IC50/XRS-6 IC50 = 1); topoisomerase II inhibitor (IC90 = 8.4 μmol/L, control Mitoxantrone, IC90 = 1.1 μmol/L); DNA intercalator (K = 54 μmol/L). Ref: L. A. McDonald, et al, JMC, 1994, 37, 3819 N O

N

H N O

401 N-Deacetylkuanoniamine D Type: Pyrido[2,3,4-kl]acridines. C18H14N4S Amorph. orange powder. Source: Sponge Oceanapia sp. (Truk, Federated States of Micronesia). Pharm: Strong affinity to benzodiazepine binding sites of GABAA receptors; cytotoxic (HeLa, IC50 = 1.2 μg/mL, Mono-Mac-6, IC50 = 2.0 μg/mL). Ref: C. Eder, et al, JNP, 1998, 61,301

150

6 Quinolines Isoquinolines and Quinazolines

N N S

N H

H 2N

402 Dehydrokuanoniamine B Type: Pyrido[2,3,4-kl]acridines. C23H20N4OS Orange solid. Source: Ascidian Cystodytes sp. (Fiji). Pharm: Cytotoxic (HCT, IC50 = 8.3 μmol/L, control Etoposide, IC50 = 2.5 μmol/L; XRS-6, IC50 = 80.0 μmol/L, Etoposide, IC50 = 0.14 μmol/L, dosedependent inhibition of proliferation); differential cytotoxicity (ratio BR1 IC50/XRS6 IC50 = 1); topoisomerase II inhibitor (IC90 = 115 μmol/L, control Mitoxantrone, IC90 = 1.1 μmol/L); DNA intercalator (K > 100 μmol/L). Ref: L. A. McDonald, et al, JMC, 1994, 37, 3819 N N S

N H 2'

HN O

403 Dehydrokuanoniamine F Type: Pyrido[2,3,4-kl]acridines. C23H20N4OS Source: Ascidian Cystodytes violatinctus (Solomon Is.). Pharm: Cytotoxic (panel of hmn tumours HTCLs, modest). Ref: N. Bontemps, et al, JNP, 2013, 76, 1801 N N S

N H

NH O

404 Deoxyamphimedine Type: Pyrido[2,3,4-kl]acridines. C19H12N3O1+ Yellow-brown amorph. solid. Source: Sponges Xestospongia cf. carbonaria (Urukthapel I., Palau, Oceania) and Xestospongia

6.1 Quinoline Alkaloids

151

spp. Pharm: Cytotoxic; DNA-cleaving agent. Ref: D. Tasdemir, et al, JOC, 2001, 66, 3246│K. M. Marshall, et al, Mar. Drugs, 2009, 7, 196│X. Wei, et al, Mar. Drugs, 2010, 8, 1769

N

N

+

N O

405 12-Deoxyascididemin Type: Pyrido[2,3,4-kl]acridines. C18H11N3 Source: Ascidian Polysyncraton echinatum (Farquharson Reef, Queensland, Australia). Pharm: Antitrypanosomal (Trypanosoma brucei brucei); cytotoxic (IC50 = 30–77 nmol/L, while exhibiting only mild cytotoxicity for control mammalian cell-line). Ref: Y. Feng, et al, Tet. Lett., 2010, 51, 2477 N N

N H

406 Dercitamine Type: Pyrido[2,3,4-kl]acridines. C19H16N4S Orange solid, mp 135 °C. Source: Sponge Stelletta sp. (deep water). Pharm: Cytotoxic (P388); immunosuppressant. Ref: G. P. Gunawardana, et al, JOC, 1992, 57, 1523 N N S

N H

HN

407 Dercitin Type: Pyrido[2,3,4-kl]acridines. C21H20N4S Deep violet hygroscopic powder, mp 168 °C. Source: Sponge Dercitus sp. (deep water). Pharm: Antineoplastic; antiviral; immunosuppressant. Ref: G. P. Gunawardana, et al, JOC, 1992, 57, 1523

152

6 Quinolines Isoquinolines and Quinazolines

N N S

N

N

408 8,9-Dihydro-11-hydroxyascididemin Type: Pyrido[2,3,4-kl]acridines. C18H11N3O2 Yellow amorph. powder, mp 300 °C. Source: Sponge Biemna sp. (Okinawa). Pharm: Cytotoxic (KB, IC50 = 0.209 μg/mL; L1210 cells, IC50 = 0.675 μg/mL). Ref: C. –M. Zeng, et al, Tetrahedron, 1993, 49, 8337 N

H N

N O

O

409 Diplamine Type: Pyrido[2,3,4-kl]acridines. C20H17N3O2S Burnt-orange solid, mp 202–204° (dec). Source: Ascidian Diplosoma sp. Pharm: Cytotoxic (HCT, IC50 < 1.4 μmol/L, control Etoposide, IC50 = 2.5 μmol/L; XRS-6, IC50 = 71.2 μmol/L, Etoposide, IC50 = 0.14 μmol/L, dose-dependent inhibition of proliferation); differential cytotoxicity (ratio BR1 IC50/ XRS-6 IC50 = 1); topoisomerase II inhibitor (IC90 = 9.2 μmol/L, control Mitoxantrone, IC90 = 1.1 μmol/L); DNA intercalator (K = 21 μmol/L); antitussive. Ref: G. A. Charyulu, et al, Tet. Lett., 1989, 30, 4201│L. A. McDonald, et al, JMC, 1994, 37, 3819 O HN

N

S

N O

410 Ecionine A Type: Pyrido[2,3,4-kl]acridines. C18H12N4O Light brown solid (trifluoroacetate salt). Source: Sponge Ecionemia geodides (Moorina Bay, Tasmania, Australia). Pharm: Cytotoxic (invasive bladder cancer TSU-Pr1, IC50 = 6.48 μmol/L, control Doxorubicin, 1 μmol/L, InRt = 96%; TSU-Pr1-B1, IC50 = 6.49 μmol/L, Doxorubicin, 1 μmol/L, InRt = 95%; TSU-Pr1-B2, IC50 = 3.55 μmol/L, Doxorubicin, 1 μmol/L, InRt = 99%; superficial bladder cancer cell line 5637, IC50 = 3.66 μmol/L,

6.1 Quinoline Alkaloids

153

Doxorubicin, 1 μmol/L, InRt = 99%). Ref: E. C. Barnes, et al, Tetrahedron, 2010, 66, 283

H N

N

N O

NH

411 Ecionine B Type: Pyrido[2,3,4-kl]acridines. C18H12N4O2 Light brown solid (trifluoroacetate salt). Source: Sponge Ecionemia geodides (Moorina Bay, Tasmania, Australia). Pharm: Cytotoxic (invasive bladder cancer TSU-Pr1-B1, 10 μmol/L, inactive, control Doxorubicin, 1 μmol/L, InRt = 95%; TSU-Pr1-B2, 10 μmol/L, InRt = 51%, Doxorubicin, 1 μmol/L, InRt = 99%; superficial bladder cancer 5637, 10 μmol/L, InRt = 54%, Doxorubicin, 1 μmol/L, InRt = 99%). Ref: E. C. Barnes, et al, Tetrahedron, 2010, 66, 283 HO

H N

N

N O

NH

412 Eilatin Type: Pyrido[2,3,4-kl]acridines. C24H12N4 Bright yellow crystal (CHCl3/MeOH/H2O), mp > 310 °C. Source: Ascidians Polysyncraton echinatum (Farquharson Reef, Queensland, Australia), Eudistoma sp. (Red Sea) and Cystodytes sp. (Red Sea). Pharm: Cytotoxic (HCT, IC50 = 13.8 μmol/L, control Etoposide, IC50 = 2.5 μmol/L, dose-dependent inhibition of proliferation); DNA intercalator (K > 100 μmol/L); Ni chelating agent. Ref: A. Rudi, et al, JOC, 1989, 54, 5331│G. Gellerman, et al, Tet. Lett., 1993, 34, 1827│L. A. McDonald, et al, JMC, 1994, 37, 3819 N

N

N

N

154

6 Quinolines Isoquinolines and Quinazolines

413 9-Hydroxyisoascididemnin Type: Pyrido[2,3,4-kl]acridines. C18H9N3O2 Amorph. yellow solid, mp 293–295 °C (dec) (Me ether). Source: Sponge Biemna fortis. Pharm: Neuronal differentiation inducer Ref: Aoki, S. et al, BoMC, 2003, 11, 1969 N O OH

N

9

N

414 Kuanoniamine A Type: Pyrido[2,3,4-kl]acridines. C16H17N3OS Yellow needles (CHCl3), mp 255–258 °C. Source: Sponge Oceanapia sagittaria (Gulf of Thailand), an unidentified ascidian and its predator prosobranch Chelynotus semperi. Pharm: Cytotoxic (KB, IC50 = 1 μg/mL); cytotoxic (MCF7 (estrogen dependent ER+), GI50 = (0.12 ± 0.07) μmol/L; MDA-MB-231 (estrogen independent ER-), GI50 = (0.73 ± 0.27)μmol/L; SF268, GI50 = (0.91 ± 0.18) μmol/L; NCI-H460, GI50 = (4.67 ± 0.20)μmol/L; UACC-62, GI50 = (1.83)μmol/L; nontumour cell line MRC-5, GI50 = (0.58 ± 0.15)μmol/L; control Doxorubicin: MCF7 (estrogen dependent ER+), GI50 = (42.8 ± 8.2)nmol/L; MDA-MB-231 (estrogen independent ER-), GI50 = (10.86 ± 1.28)nmol/L; SF268, GI50 = (94.0 ± 7.0)nmol/L; NCI-H460, GI50 = (94.0 ± 8.7)nmol/L; UACC62, GI50 = (94.0 ± 9.4)nmol/L). Ref: A. R. Carroll, et al, JOC, 1990, 55, 4426│A. Kijjoa, et al, Mar. Drugs, 2007, 5, 6 N N S

N O

415 Kuanoniamine B Type: Pyrido[2,3,4-kl]acridines. C23H22N4OS Amorph. yellow powder (CHCl3), mp 300 °C. Source: An unidentified ascidian and its predator prosobranch Chelynotus semperi (depth of 25m, Mante Channel, Pohnpei I., Federated States of Micronesia, Oct 1987). Pharm: Cytotoxic (KB, IC50 > 10 μg/mL). Ref: A. R. Carroll, et al, JOC, 1990, 55, 4426

6.1 Quinoline Alkaloids

155

N N S

N H

HN O

416 Kuanoniamine C Dercitamide Type: Pyrido[2,3,4-kl]acridines. C21H18N4OS Amorphous yellow powder, (CHCl3), mp 300 °C, mp 192 °C. Source: Sponges Oceanapia sp. (Truk, Federated States of Micronesia), Oceanapia sagittaria (Gulf of Thailand) and Stelletta sp. (deep water), an unidentified ascidian and its predator prosobranch Chelynotus semperi ((depth of 25 m, Mante Channel, Pohnpei I., Federated States of Micronesia, Oct 1987), ascidian Cystodytes sp. and its predator prosobranch Chelynotus semperi. Pharm: Cytotoxic (MCF7 (estrogen dependent ER+), GI50 = (0.81 ± 0.11)μmol/L; MDA-MB-231 (estrogen independent ER-), GI50 = (10.23 ± 3.35)μmol/L; SF268, GI50 = (21.50 ± 2.44)μmol/L; NCIH460, GI50 = (33.16) μmol/L; UACC-62, GI50 = (15.78)μmol/L); control Doxorubicin: MCF7 (estrogen dependent ER+), GI50 = (42.8 ± 8.2)nmol/L; MDA-MB-231 (estrogen independent ER-), GI50 = (10.86 ± 1.28)nmol/L; SF268, GI50 = (94.0 ± 7.0)nmol/L; NCI-H460, GI50 = (94.0 ± 8.7)nmol/L; UACC62, GI50 = (94.0 ± 9.4)nmol/L); cytotoxic (P388); insecticide (neonate larvae of polyphagous pest insect Spodoptera littoralis, LC50 = 156 ppm); has strong affinity to benzodiazepine binding sites of GABAA receptors; immunosuppressant; toxic (brine shrimp lethality, LC50 = 37 μmol/L). Ref: G. P. Gunawardana, et al, Tet. Lett., 1989, 30, 4359│A. R. Carroll, et al, JOC, 1990, 55, 4426│C. Eder, et al, JNP, 1998, 61, 301│A. Kijjoa, et al, Mar. Drugs, 2007, 5, 6 N N S

N H

HN O

156

6 Quinolines Isoquinolines and Quinazolines

417 Kuanoniamine D Type: Pyrido[2,3,4-kl]acridines. C20H16NO4S Amorph. yellow powder (CHCl3), mp 300 °C. Source: Sponge Oceanapia sp. (Truk, Federated States of Micronesia), an unidentified ascidian and its predator prosobranch Chelynotus semperi (depth of 25 m, Mante Channel, Pohnpei I., Federated States of Micronesia, Oct 1987), ascidian Cystodytes sp. (Fiji). Pharm: Cytotoxic (KB, IC50 = 5 μg/mL) (Carroll, 1990); cytotoxic (in vitro, HCT, IC50 = 7.8 μmol/L, control Etoposide, IC50 = 2.5 μmol/L; XRS-6 cells, IC50 = 88.9 μmol/L, Etoposide, IC50 = 0.14 μmol/L, dose-dependent inhibition of proliferation) (McDonald, 1994); differential cytotoxicity (ratio BR1 IC50/XRS-6 IC50 = 2); topoisomerase II inhibitor (IC90 = 127 μmol/L, control Mitoxantrone, IC90 = 1.1 μmol/ L); DNA intercalator (K = 62 μmol/L); affinity to adenosine receptors (strong affinity to A1-adenosine receptors, Ki = 2.94 μmol/L, A2-adenosine receptors, Ki = 13.7 μmol/ L, benzodiazepine binding sites of GABAA receptors) (Eder, 1998); chelating agent; insecticide (neonate larvae of polyphagous pest insect Spodoptera littoralis, LC50 = 59 ppm) (Eder, 1998); toxic (brine shrimp lethality, LC50 = 19 μg/mL). Ref: A. R. Carroll, et al, JOC, 1990, 55, 4426│G. P. Gunawardana, et al, JOC, 1992, 57, 1523│L. A. McDonald, et al, JMC, 1994, 37, 3819│C. Eder, et al, JNP, 1998, 61,301 N N S

N H 2'

HN O

418 Labuanine A Type: Pyrido[2,3,4-kl]acridines. C18H11N3O2 Amorph. yellow solid. Source: Sponge Biemna fortis. Pharm: Neuronal differentiation inducer. Ref: S. Aoki, et al, BoMC, 2003, 11, 1969 N OH O

N N

419 Meridine Type: Pyrido[2,3,4-kl]acridines. C18H9N3O2 Yellow amorph. solid, mp 250 °C. Source: Sponge Ecionemia geodides (Moorina Bay, Tasmania, Australia) and Corticium sp., ascidian Amphicarpa meridian. Pharm: Cytotoxic (invasive bladder cancer TSU-Pr1,

6.1 Quinoline Alkaloids

157

IC50 = 3.77 μmol/L, control Doxorubicin, 1 μmol/L, InRt = 96%; TSU-Pr1-B1, IC50 = 4.56 μmol/L, Doxorubicin, 1 μmol/L, InRt = 95%; TSU-Pr1-B2, IC50 = 3.76 μmol/ L, Doxorubicin, 1 μmol/L, InRt = 99%; superficial bladder cancer 5637, 10 μmol/L, InRt = 37%, Doxorubicin, 1 μmol/L, 99%); antifungal. Ref: F. J. Schmitz, et al, JOC, 1991, 56, 804│P. J. McCarthy, et al, JNP, 1992, 55, 1664│Y. Kitahara, et al, CPB, 1994, 42, 1363│Y. Kitahara, et al, Tetrahedron, 1998, 54, 8421│E. C. Barnes, et al, Tetrahedron, 2010, 66, 283 N O

N

N

HO

420 Neoamphimedine Type: Pyrido[2,3,4-kl]acridines. C19H11N3O2 Yellow solid, mp > 300 °C. Source: Sponges Xestospongia cf. carbonaria (Urukthapel I., Palau, Oceania) and Xestospongia cf. exigua. Pharm: Cytotoxic; topoisomerase II inhibitor (catenates DNA). Ref: X. Wei, et al, Mar. Drugs, 2010, 8, 1769│F. S. De Guzman, et al, JOC, 1999, 64, 1400│K. M. Marshall, et al, Biochem. Pharmacol., 2003, 66, 447

N

N

N O

O

421 Nordercitin Type: Pyrido[2,3,4-kl]acridines. C20H18N4S Yellowsolid, mp 176 °C. Source: Sponge Stelletta sp. (deep water). Pharm: Cytotoxic (P388, cell proliferation inhibitor); immunosuppressant. Ref: G. P. Gunawardana, et al, Tet. Lett., 1989, 30, 4359│G. P. Gunawardana, et al, JOC, 1992, 57, 1523 N S N

N H

N

158

6 Quinolines Isoquinolines and Quinazolines

422 Pantherinine Type: Pyrido[2,3,4-kl]acridines. C15H8BrN3O Purple powder, mp > 300 °C. Source: Ascidian Aplidium pantherinum. Pharm: Cytotoxic (P388). Ref: J. Kim, et al, JNP, 1993, 56, 1813│S. Nakahara, et al, Tet. Lett., 1998, 39, 5521 N O

Br

H 2N

N

423 Perophoramidine Type: Pyrido[2,3,4-kl]acridines. C21H17BrCl2N4 Amorph. off–white solid, [α]D25 = +3.8° (c = 0.7, CHCl3). Source: Ascidian Perophora nameii (Philippine). Pharm: Cytotoxic (HCT116, IC50 = 60 μmol/L, induces apoptosis via PARP cleavage within 24h) Ref: S. M. Verbitski, et al, JOC, 2002, 67, 7124│H. Wu, JACS, 2010, 132, 14052

N

N

Cl

Br

N

N H

Cl

424 Sebastianine A Type: Pyrido[2,3,4-kl]acridines. C17H9N3O Amorph. yellow solid. Source: Ascidian Cystodytes dellechiajei (Brazil). Pharm: Cytotoxic (against HCT cells in p53 dependent manner, p53+/+ tumor cell lines, IC50 = 5.1 μmol/L, p53–/– tumor cell lines, IC50 = 9.7 μmol/L). Ref: Y. R. Torres, et al, JOC, 2002, 67, 5429 N O

N

N H

425 Sebastianine B Type: Pyrido[2,3,4-kl]acridines. C22H19N3O3 Pale yellow solid. Source: Ascidian Cystodytes dellechiajei (Brazil). Pharm: Cytotoxic (against HCT cells in p53 dependent manner, p53+/+ tumor cell lines, IC50 = 0.92 μmol/L, p53–/– tumor cell lines, IC50 = 2.9 μmol/L). Ref: Y. R. Torres, et al, JOC, 2002, 67, 5429

6.1 Quinoline Alkaloids

N

159

OH O

N

N

O

426 Segoline A Type: Pyrido[2,3,4-kl]acridines. C23H19N3O3 Amorph. powder, mp 276 °C, [α]D24 = −322° (c = 1, CHCl3). Source: Ascidian Eudistoma sp. (Red Sea). Pharm: Cell proliferation inhibitor. Ref: A. Rudi, et al, JOC, 1989, 54, 5331│I. Viracaoundin, et al, Tet. Lett., 2001, 42, 2669 N O N 16 9

O

13

H O

N H

427 Shermilamine B Type: Pyrido[2,3,4-kl]acridines. C21H18N4O2S Fine orange prisms (MeOH), mp 254 °C (dec). Source: An unidentified ascidian and its predator prosobranch Chelynotus semperi (depth of 25 m, Mante Channel, Pohnpei I., Federated States of Micronesia, Oct 1987), ascidians Cystodytes sp. (Fiji), Trididemnum sp., Eudistoma sp. (Red Sea) and predator prosobranch Chelynotus semperi. Pharm: Cytotoxic (KB, IC50 = 5 μg/mL) (Carroll, 1990); cytotoxic (in vitro, HCT, IC50 = 13.8 μmol/L, control Etoposide, IC50 = 2.5 μmol/L; XRS-6 cells, IC50 = 14.9 μmol/L, Etoposide, IC50 = 0.14 μmol/L, dosedependent inhibition of proliferation) (McDonald, 1994); differential cytotoxicity (ratio BR1 IC50/XRS-6 IC50 = 1); topoisomerase II inhibitor (IC90 = 118 μmol/L, control Mitoxantrone, IC90 = 1.1 μmol/L); DNA intercalator (K > 100 μmol/L). Ref: A. R. Carroll, et al, JOC, 1989, 54, 4231│A. Rudi, et al, JOC, 1989, 54, 5331│A. R. Carroll, et al, JOC, 1990, 55, 4426│L. A. McDonald, et al, JMC, 1994, 37, 3819

O

H N

N

N H

S

HN O

160

6 Quinolines Isoquinolines and Quinazolines

428 Shermilamine C Type: Pyrido[2,3,4-kl]acridines. C24H22N4O2S Orange solid. Source: Ascidian Cystodytes sp. (Fiji). Pharm: Cytotoxic (HCT, IC50 = 16.3 μmol/L, control Etoposide, IC50 = 2.5 μmol/L; XRS-6, IC50 = 8.1 μmol/L, Etoposide, IC50 = 0.14 μmol/L, dosedependent inhibition of proliferation); differential cytotoxicity (ratio BR1 IC50/XRS6 IC50 = 1); topoisomerase II inhibitor (IC90 = 138 μmol/L, control Mitoxantrone, IC90 = 1.1 μmol/L); DNA intercalator (K > 100 μmol/L). Ref: L. A. McDonald, et al, JMC, 1994, 37, 3819

O

H N

N

N H

S

HN O

429 Shermilamine D Type: Pyrido[2,3,4-kl]acridines. C21H20N4OS Amorph. orange powder. Source: Ascidian Cystodytes violatinctus (Comoros). Pharm: Antineoplastic; antiviral. Ref: G. Koren-Goldschlager, et al, JOC, 1998, 63, 4601

O

H N

N

S

N H

N

430 Shermilamine E Type: Pyrido[2,3,4-kl]acridines. C21H20N4O2S Amorph. brown powder. Source: Ascidian Cystodytes violatinctus (Comoros). Pharm: Antineoplastic; antiviral. Ref: G. Koren-Goldschlager, et al, JOC, 1998, 63, 4601

O

H N

N

H N

S

O N

6.1 Quinoline Alkaloids

161

431 Shermilamine F Type: Pyrido[2,3,4-kl]acridines. C24H22N4O2S Source: Ascidian Cystodytes violatinctus (Solomon Is.). Pharm: Cytotoxic (panel of hmn tumours HTCLs, modest). Ref: N. Bontemps, et al, JNP, 2013, 76, 1801 N

N H

H N

O

S

NH O

432 Styelsamine A Type: Pyrido[2,3,4-kl]acridines. C17H16N3O21+ Purple solid (bistrifluoroacetate salt). Source: Ascidian Eusynstyela latericius (Indonesia). Pharm: Cytotoxic (HCT116, IC50 = 33 μmol/L). Ref: B. R. Copp, et al, JOC, 1998, 63, 8024 H

+

N

HO

N H HO NH2

433 Styelsamine B Type: Pyrido[2,3,4-kl]acridines. C19H18N3O21+ Purple solid (bistrifluoroacetate salt). Source: Ascidian Eusynstyela latericius (Indonesia). Pharm: Cytotoxic (HCT116, IC50 = 89 μmol/L). Ref: B. R. Copp, et al, JOC, 1998, 63, 8024│D. Skyler, et al, Org. Lett., 2001, 3, 4323 H

+

N

HO

N H

NH O

162

6 Quinolines Isoquinolines and Quinazolines

434 Styelsamine C Type: Pyrido[2,3,4-kl]acridines. C16H11N2O21+ Orange solid (trifluoroacetate salt). Source: Ascidian Eusynstyela latericius (Indonesia). Pharm: Cytotoxic (HCT116, IC50 = 2.8 μmol/L). Ref: B. R. Copp, et al, JOC, 1998, 63, 8024 H

N

+

HO

N H O

H

435 Styelsamine D Type: Pyrido[2,3,4-kl]acridines. C17H16N3O1+ Purple solid (bistrifluoroacetate salt). Source: Ascidian Eusynstyela latericius (Indonesia). Pharm: Cytotoxic (HCT116, IC50 = 1.6 μmol/L). Ref: B. R. Copp, et al, JOC, 1998, 63, 8024 H

+

N

HO

N H

NH2

436 Tintamine Type: Pyrido[2,3,4-kl]acridines. C20H21N3O2S Source: Ascidian Cystodytes violatinctus (Comoros). Pharm: Antineoplastic; antiviral. Ref: G. Koren-Goldschlager, et al, JOC, 1998, 63, 4601

HO

N OH

N

N S

437 Varamine A Type: Pyrido[2,3,4-kl]acridines. C22H23N3O2S Orange solid. Source: Ascidian Lissoclinum vareau. Pharm: Cytotoxic (L1210, IC50 = 0.03 μg/mL); topoisomerase inhibitor. Ref: T. F. Molinski, et al, JOC, 1989, 54, 4256

6.2 Isoquinoline Alkaloids

163

N O

N H

S

HN O

438 Varamine B Type: Pyrido[2,3,4-kl]acridines. C21H21N3O2S Orange solid. Source: Ascidian Lissoclinum vareau. Pharm: Cytotoxic (L1210, IC50 = 0.03 μg/mL); topoisomerase inhibitor. Ref: T. F. Molinski, et al, JOC, 1989, 54, 4256 N O

N H

S

HN O

6.2 Isoquinoline Alkaloids 439 7-Amino-7-demethoxymimosamycin Type: Isoquinoline alkaloids. C11H10N2O3 Light brown solid, mp 300 °C. Source: Sponge Petrosia sp. (India waters). Pharm: cAMP inhibitor. Ref: M. Kobayashi, et al, J. Chem. Res. (S), 1994, 282 O O N

H 2N O

440 4-Aminomimosamycin Type: Isoquinoline alkaloids. C12H12N2O4 Deep red needles, mp 250–251 °C. Source: Sponge Petrosia sp. (India waters). Pharm: cAMP inhibitor. Ref: M. Kobayashi, et al, J. Chem. Res. (S), 1994, 282

164

6 Quinolines Isoquinolines and Quinazolines

O

NH2 4

O

O N

7

O

441 Cribrostatin 1 Type: Isoquinoline alkaloids. C11H10N2O2 Red-orange crystal (CH2Cl2/MeOH), mp 220–235 °C (dec). Source: Sponge Cribrochalina sp. (Maldives). Pharm: Cytotoxic (P388, ED50 = 1.58 μg/mL); antibacterial (Neisseria gonorrheae ATCC 49226, MIC = 0. 39–0.78 μg/disk; PRNG (clinical isolate), MIC = 0.39–0.78 μg/disk). Ref: G. R. Prttit, et al, Can. J. Chem., 1992, 70, 1170│S. Nakahara, et al, Heterocycles, 1995, 41, 651│G. R. Pettit, et al, JNP, 2000, 63, 793 O

N

H 2N O

442 Cribrostatin 2 Type: Isoquinoline alkaloids. C13H13NO4 Golden-yellow solid, mp 194–195 °C. Source: Sponge Cribrochalina sp. (Maldives). Pharm: Cytotoxic (P388, ED50 = 2.73 μg/mL); antifungal (Candida albicans ATCC 90028, MIC = 3.12–6.25 μg/mL; Cryptococcus neoformans ATCC 90112, MIC = 12.5–25 μg/mL; Micrococcus luteus, MIC = 50–100 μg/mL); antibacterial (Neisseria gonorrheae ATCC 49226, MIC = 6.25–12.5 μg/disk; PRNG (clinical isolate), MIC = 1.56–3.12 μg/disk; Bacillus subtilis, MIC = 12.5–25 μg/disk; Streptococcus pneumoniae ATCC 6303, MIC = 6.25–12.5 μg/disk; PRSP (clinical isolate), MIC = 50–100 μg/disk). Ref: G. R. Prttit, et al, Can. J. Chem., 1992, 70, 1170│S. Nakahara, et al, Heterocycles, 1995, 41, 651│G. R. Pettit, et al, JNP, 2000, 63, 793 O O N

O O

443 Cribrostatin 3 Type: Isoquinoline alkaloids. C16H16N2O4 Orange-red needles (CH2Cl2/MeOH), mp 190–192 °C. Source: Sponge Cribrochalina sp. Pharm: Cytotoxic (BXPC3, GI50 > 1 μg/ mL; OVCAR-3, GI50 = 0.77 μg/mL; SF295, GI50 > 1 μg/mL; NCI-H460, GI50 > 1 μg/mL;

6.2 Isoquinoline Alkaloids

165

KM20L2, GI50 > 1 μg/mL; DU145, GI50 > 1 μg/mL; P388, GI50 = 2.49 μg/mL); antibacterial (Neisseria gonorrheae ATCC 49226, MIC = 0.0975–0.195 μg/disk; PRNG (clinical isolate), MIC = 0.39–0.78 μg/disk). Ref: G. R. Pettit, et al, JNP, 2000, 63, 793 O

N

H 2N O

O O

444 Cribrostatin 5 Type: Isoquinoline alkaloids. C17H18N2O4 Red-brown plates (MeOH/CH2Cl2). Source: Sponge Cribrochalina sp. Pharm: Cytotoxic (BXPC3, GI50 = 0.29 μg/mL; OVCAR-3, GI50 = 0.18 μg/mL; CNS SF295, GI50 = 0.36 μg/mL; NCI-H460, GI50 = 0.22 μg/mL; KM20L2, GI50 = 0.14 μg/mL; DU145, GI50 > = 0.30 μg/mL; P388, GI50 = 0.045 μg/mL); antibacterial (Neisseria gonorrheae ATCC 49226, MIC = 6.25–12.5 μg/disk; PRNG (clinical isolate), MIC = 6.25–12.5 μg/disk); antibacterial (Micrococcus luteus (Presque Isle 456), MIC = 50–100 μg/disk). Ref: G. R. Pettit, et al, JNP, 2000, 63, 793 O

N

N H

O O O

445 Cribrostatin 6 Type: Isoquinoline alkaloids. C15H14N2O3 Dark blue needles (Me2CO), mp 169–171 ° C. Source: Sponge Cribrochalina sp. Pharm: Cytotoxic (cancer cell growth inhibitor); antibacterial. Ref: Pettit, G.R. et al, JNP, 2003, 66, 544│R. K. Pettit, et al, J. Med. Microbiol., 2004, 53, 61 O

N

O O

N

166

6 Quinolines Isoquinolines and Quinazolines

446 O-Demethylrenierol acetate Type: Isoquinoline alkaloids. C13H11NO5 Yellow oil. Source: Sponge Petrosia sp. (India waters). Pharm: Antibacterial. Ref: Y. Venkateswarlu, et al, Ind. J. Chem., Sect. B, 1993, 32, 704 O

N

HO O

O

O

447 O-Demethylrenierone Type: Isoquinoline alkaloids. C16H15NO5 Orange solid, mp 135–136 °C. Source: Sponges Cribrochalina sp. (Maldives) and Reniera sp. Pharm: Antibacterial. Ref: D. E. Mclntyre, et al, Tet. Lett., 1979, 4163│ G. R. Pettit, et al, Can. J. Chem., 1992, 70, 1170 O

N

HO O

O

O

448 (–)-N-Formyl-1,2-dihydrorenierone Type: Isoquinoline alkaloids. C18H19NO6 Red non-cryst. solid, [α]D20 = −227° (c = 0.023, MeOH). Source: Sponge Reniera sp. (Fiji). Pharm: Toxic (inhibits cell division in fertilized sea urchin egg). Ref: J. M. Frincke, et al, JACS, 1982, 104, 265 O

N

O O

O

H O O

449 4-Hydroxy-1-(3-hydroxyphenyl)-3(2H)-isoquinolinone Phomopsin A‡ Type: Isoquinoline alkaloids. C15H11NO3 Amorph. solid, mp 250–252 °C. Source: Mangrove-derived fungus Phomopsis sp. ZZ08 from an unidentified mangrove

6.2 Isoquinoline Alkaloids

167

(China waters). Pharm: Cytotoxic (two cell lines, mild). Ref: Y. Tao, et al, Magn. Reson. Chem., 2008, 46, 501 OH O NH

OH

450 7-Methoxy-1,6-dimethyl-5,8-isoquinolinedione Type: Isoquinoline alkaloids. C12H11NO3 mp 188–190 °C (dec). Source: Sponges Reniera sp. and Xestospongia sp. Pharm: Antibacterial (gram-positive bacteria, weak); insecticide. Ref: D. E. Mclntyre, et al, Tet. Lett., 1979, 4163│J. M. Frincke, et al, JACS, 1982, 104, 265│A. Kubo, et al, CPB, 1985, 33. 2582│R. A. Edrada, et al, JNP, 1996, 59, 973 O

N O O

451 N-Methylnorsalsolinol Type: Isoquinoline alkaloids. C10H13NO2 Source: Sponge Xestospongia sp. (Bougainville Reef, Queensland) Pharm: Antioxidant (radical scavenger). Ref: N. K. Utkina, et al, Chem. Nat. Compd., 2012, 48, 715 HO

HO

N

452 Mimosamycin Type: Isoquinoline alkaloids. C12H11NO4 Yellow prisms (MeOH), mp 227–232 °C, mp 219–221 °C, [α]D24 = −1.8° (c = 1, MeOH). Source: Sponges Halichondria spp., Reniera spp., Xestospongia spp., Petrosia spp. and Oceanapia sp. Pharm: Antibacterial (Staphylococcus aureus, 50 μg, DIZ = 14 mm/disk; Bacillus subtilis, 50 μg, DIZ = 11 mm/ disk; Vibrio anguillarum, 10 μg, DIZ = 11 mm/disk; B-392, 10 μg, DIZ = 10 mm/disk); antifungal (Candida albicans, 50 μg, DIZ = 9 mm/disk). Ref: T. Arai, et al, J. Antibiot., 1976, 29, 398│J. M. Frincke, et al, JACS, 1982, 104, 265│M. Kobayashi, et al, J. Chem. Res., Synop., 1994, 282│CRC press, DNP, on DVD, 2012, version 20.2

168

6 Quinolines Isoquinolines and Quinazolines

O O N

O O

453 Perfragilin A Type: Isoquinoline alkaloids. C11H10N2O3S Red needles, mp 219–220 °C. Source: Bryozoan Membranipora perfragilis (Southern Australia). Pharm: Cytotoxic (P388). Ref: Y. -H. Choi, et al, JNP, 1993, 56, 1431│S. K. Rizvi, et al, Acta Cryst. Sect. C, 1993, 49, 151 O S

O N

H 2N O

454 Perfragilin B Type: Isoquinoline alkaloids. C12H11NO3S2 Red needles, mp 163 °C. Source: An unidentified bryozoan (Bass Strait, Tasmania, Australia), bryozoan Membranipora perfragilis (Southern Australia). Pharm: Cytotoxic (P388). Ref: A. J. Blackman, et al, Aust. J. Chem., 1993, 46, 213│Y. -H. Choi, et al, JNP, 1993, 56, 1431 O S

O 7

N

S O

455 Renierol Type: Isoquinoline alkaloids. C12H11NO4 Source: Sponge Xestospongia caycedoi (Fiji). Pharm: Antibiotic. Ref: T. C. McKee, et al, JNP, 1987, 50, 754 O

N

O O

OH

6.2 Isoquinoline Alkaloids

169

456 Renierone Type: Isoquinoline alkaloids. C17H17NO5 mp 91.5–92.5 °C. Source: Sponges Reniera sp. and Cribrochalina sp. (Maldives). Pharm: Antibacterial (Staphylococcus aureus, 10 μg, DIZ = 8 mm/disk; Bacillus subtilis, 10 μg, DIZ = 10 mm/disk; Escherichia coli, 10 μg, DIZ = 8 mm/disk); antifungal; antineoplastic. Ref: J. M. Frincke, et al, JACS, 1982, 104, 265│G. R. Pettit, et al, Can. J. Chem., 1992, 70, 1170│D. E. Mclntyre, et al, Tet. Lett., 1979, 4163 O

N

O O

O O

457 Saldedine A Type: Isoquinoline alkaloids. C18H17Br2NO3 Cryst. Source: An unidentified ascidian (Salary Bay, Madagascar). Pharm: Toxic (brine shrimp, modest). Ref: H. Sorek, et al, J. Nat. Prod., 2009, 72, 784 O N

HO Br O

Br

458 Saldedine B Type: Isoquinoline alkaloids. C18H19Br2NO3 Oil, [α]D20 = −50° (c = 0.2, MeOH). Source: An unidentified ascidian (Salary Bay, Madagascar). Pharm: Toxic (brine shrimp, modest). Ref: H. Sorek, et al, J. Nat. Prod., 2009, 72, 784 O N

HO Br HO

Br

170

6 Quinolines Isoquinolines and Quinazolines

459 Theoneberine Type: Isoquinoline alkaloids. C27H25Br4NO6 Colorless solid, mp 128 °C, [α]D20 = −53° (c = 0.6, CHCl3). Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Antibacterial (gram-positive bacteria MIC = 16 μg/mL; Staphylococcus aureus MIC = 2 μg/mL; Sarcina lutea MIC = 66 μg/mL; Bacillus subtilis MIC = 4 μg/mL; Mycobacterium sp.); cytotoxic (L1210, IC50 = 10 μg/mL; KB, IC50 = 2.9 μg/mL). Ref: J. Kobayashi, et al, JOC, 1992, 57, 6680 O Br

HO

Br O

N

HO Br

H

H

OH

O Br

460 Aaptamine Type: Aaptamines alkaloids. C13H12N2O2 Brilliant green cryst; bright yellow cryst. (MeOH/Me2CO) (hydrochloride), mp 110–113 °C, mp 107 °C (hydrochloride). Source: Sponge Aaptos aaptos. Pharm: α-Adrenoreceptor blocker; antineoplastic. Ref: H. Nakamura, et al, JCS Perkin I, 1987, 173│L. Calcul, et al, Tetrahedron, 2003, 59, 6539│E. L. Larghi, et al, Tetrahedron, 2009, 65, 4257 O 9

N

O HN

461 9-De-O-methylaaptamine Type: Aaptamines alkaloids. C12H10N2O2 Greenish–yellow powder +1.5H2O (hydrochloride), mp 248–251 °C (dec) (hydrochloride). Source: Sponge Aaptos aaptos. Pharm: Cytotoxic; antimicrobial. Ref: H. Nakamura, et al, JCS Perkin I, 1987, 173 O N HO

9

HN

6.2 Isoquinoline Alkaloids

171

462 Demethyloxyaaptamine Type: Aaptamines alkaloids. C12H18N2O2 Fine bright yellow rods (EtOAc), mp 210–212 °C, mp 198–200 °C. Source: Sponges Aaptos aaptos and Xestospongia sp. Pharm: Cytotoxic; antibacterial (gram-positive and -negative bacteria). Ref: H. Nakamura, et al, JCS Perkin I, 1987, 173 O N O

9

N

463 Isoaaptamine Type: Aaptamines alkaloids. C13H12N2O2 Amorph. yellow powder, mp 200–205 °C (dec). Source: Sponges Aaptos aaptos, Hymeniacidon sp. and Suberites sp. Pharm: Antibacterial (Staphylococcus aureus, IC50 = 3.7 μg/mL, MMOA: sortase A inhibitor and fibronectin binding); antineoplastic; β-glucanase inhibitor. Ref: K. H. Jang, et al, BoMCL, 2007, 17, 5366│V. V. Sova, et al, Chem. Nat. Compd. (Engl. Transl.), 1990, 26, 420│A. M. S. Mayer, et al, Comparative Biochemistry and Physiology, Part C 153, 2011, 191 (rev) O 9

N

HO N

464 N4-Methylaaptamine Type: Aaptamines alkaloids. C14H14N2O2 Pale yellow oil. Source: Sponge Aaptos aaptos. Pharm: Antiviral. Ref: A. F. Coutinho, et al, Heterocycles, 2002, 57, 1265 O 9

N

O N

465 3-(4-Morpholinyl)demethyloxyaaptamine Type: Aaptamines alkaloids. C16H15N3O3 Orange powder. Source: Sponge Aaptos sp. (Vang Fong Bay, Vietnam). Pharm: Cytotoxic (inibitor of EGF-induced malignant transformation of murine epidermal cells). Ref: L. K. Shubina, et al, Nat. Prod. Commun., 2009, 4, 1085

172

6 Quinolines Isoquinolines and Quinazolines

O O

N N N

O

466 Suberitine A Type: Aaptamines alkaloids. C28H26N4O6 Source: Sponge Aaptos suberitoides (Xisha Is., South China Sea). Pharm: Cytotoxic (P388, low micromolar inhibitor). Ref: C. Liu, et al, Org. Lett., 2012, 14, 1994

O

O

N

N

O N

N O O

O

467 Suberitine B Type: Aaptamines alkaloids. C6H20N4O5 Source: Sponge Aaptos suberitoides (Xisha Is., South China Sea). Pharm: Cytotoxic (P388, low micromolar inhibitor). Ref: C. Liu, et al, Org. Lett., 2012, 14, 1994 O O

N

N

O N

N O

O

468 Suberitine C Type: Aaptamines alkaloids. C28H26N4O6 Source: Sponge Aaptos suberitoides (Xisha Is., South China Sea). Pharm: Cytotoxic (P388, low micromolar inhibitor). Ref: C. Liu, et al, Org. Lett., 2012, 14, 1994

O

O

N

N

O

O O

O N

N

6.3 Quinazoline Alkaloids

173

469 Suberitine D Type: Aaptamines alkaloids. C6H20N4O5 Source: Sponge Aaptos suberitoides (Xisha Is., South China Sea). Pharm: Cytotoxic (P388, low micromolar inhibitor). Ref: C. Liu, et al, Org. Lett., 2012, 14, 1994

O

O

N

N

O O

O N

N

6.3 Quinazoline Alkaloids 470 Aniquinazoline A Type: Quinazoline alkaloids. C26H25N5O4 Colorless crystal, mp 243–245 °C, [α]D20 = −13° (c = 0.30, MeOH). Source: Mangrove-derived fungus Aspergillus nidulans MA143 (endophytic) from mangrove Rhizophora stylosa (leaves, unspecified location, presumably China). Pharm: Toxic (brine shrimp, LD50 = 1.27 mmol/L, control Colchicines, LD50 = 88.4 mmol/L). Ref: C.-Y. An, et al, Mar. Drugs, 2013, 11, 2682

O

N H N H

O HN

N N

O O

471 Aniquinazoline B Type: Quinazoline alkaloids. C26H27N5O4 Yellowish solid, [α]D20 = −118° (c = 0.28, MeOH). Source: Mangrove-derived fungus Aspergillus nidulans MA-143 (endophytic) from mangrove Rhizophora stylosa (leaves, unspecified location, presumably China). Pharm: Toxic (brine shrimp, LD50 = 2.11 mmol/L, control Colchicines, LD50 = 88.4 mmol/L). Ref: C.-Y. An, et al, Mar. Drugs, 2013, 11, 2682

H O

N H

OH

N

HN N

N H O

O

174

6 Quinolines Isoquinolines and Quinazolines

472 Aniquinazoline C Type: Quinazoline alkaloids. C26H27N5O5 Yellowish solid, [α]D20 = −19° (c = 0.28, MeOH). Source: Mangrove-derived fungus Aspergillus nidulans MA-143 (endophytic) from mangrove Rhizophora stylosa (leaves, unspecified location, presumably China). Pharm: Toxic (brine shrimp, LD50 = 4.95 mmol/L, control Colchicines, LD50 = 88.4 mmol/L). Ref: C.-Y. An, et al, Mar. Drugs, 2013, 11, 2682

OH OH

N H

O

N

HN N

N H

O

O

473 Chrysogine Type: Quinazoline alkaloids. C10H10N2O2 Source: Deep-sea fungus Penicillium commune SD-118 (sediment). Pharm: Cytotoxic (SW1990, IC50 = 20.0 μg/mL). Ref: Z. Shang, et al, Chin. J. Oceanol. Limnol., 2012, 30, 305 O NH N OH

474 Deoxynortryptoquivaline Type: Quinazoline alkaloids. C28H28N4O6 White solid, [α]D25 = +60° (c = 0.1, CHCl3), [α]D25 = +69.5° (c = 0.82, CHCl3). Source: Mangrove-derived fungus Cladosporium sp. PJX-41. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 87 μmol/L, control Ribavirin, IC50 = 87 μmol/L). Ref: J. Buchi, et al, Org. Chem., 1977, 42, 244│J. Peng, et al, JNP, 2013, 76, 1133 O N

O

27S

O

N

O

O 2R

N O

NH H

6.3 Quinazoline Alkaloids

175

475 Deoxytryptoquivaline Type: Quinazoline alkaloids. C29H30N4O6 [α]D25 = +50° (c = 0.1, CHCl3), [α]D25 = +56.8° (c = 0.78, CHCl3). Source: Mangrove-derived fungus Cladosporium sp. PJX-41. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 85 μmol/L, control Ribavirin, IC50 = 87 μmol/L). Ref: J. Buchi, et al, Org. Chem., 1977, 42, 244│J. Peng, et al, JNP, 2013, 76, 1133 O N

O

27S

O

N

O

O 2R

NH

N O

476 Monodontamide F Type: Quinazoline alkaloids. C25H27N5O5 Source: Prosobranch Monodonta labio (Japan waters). Pharm: Serine protease inhibitor (weak). Ref: H. Niwa, et al, Tetrahedron, 1994, 50, 6805 O

H N

H N

N

O

N

O

O

HN O

477 Penipanoid C 2-(4-Hydroxybenzoyl) quinazolin-4(3H)-one Type: Quinazoline alkaloids. C15H10N2O3 Yellowish solid. Source: Marine-derived fungi Penicillium paneum (sediment, South China Sea) and Penicillium oxalicum 0312f1. Pharm: Antibacterial (Staphylococcus aureus and Escherichia coli); antifungal (Alternaria brassicae, Fusarium oxysporium f. sp. vasinfectum, Coniella diplodiella, Physalospora piricola and Aspergillus niger). Ref: S. Shen, et al, Acta Microbiol. Sinic., 2009, 49, 1240│C. -S. Li, et al, JNP, 2011, 74, 1331│S. Shen, et al, Nat. Prod. Res., 2013, 27, 2286 O OH

NH N O

176

6 Quinolines Isoquinolines and Quinazolines

478 Shewanelline C Type: Quinazoline alkaloids. C16H11N3O3 Source: Deep-sea bacterium Shewanella piezotolerans WP3. Pharm: Cytotoxic (HL60, IC50 = 5.91 μg/mL; Bel7402, IC50 = 10.03 μg/mL). Ref: Y. Wang, et al, J. Antibiot., 2014, 67, 395 H N

1

O

3R

H O

N

O

NH

479 Tryptoquivaline Type: Quinazoline alkaloids. C29H30N4O7 Colorless crystals (MeOH−H2O), mp 215 °C, [α]D25 = +120° (c = 0.1, CHCl3), [α]D25 = +130° (c = 0.22, CHCl3). Source: Mangrovederived fungus Cladosporium sp. PJX-41. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 89 μmol/L, control Ribavirin, IC50 = 87 μmol/L). Ref: J. Buchi, et al, Org. Chem., 1977, 42, 244│J. Peng, et al, JNP, 2013, 76, 1133 O N

O

27S

O

N

O

O 2S

N O

OH N

7 Pyrimidines and Pyrazines 7.1 Pyrimidines 480 Auranomide A Type: Pyrimidines. C19H16N4O3 White amorph. powder, [α]D20 = +14.9° (c = 0.10, MeOH). Source: Marine-derived fungus Penicillium aurantiogriseum (mud, Bohai Sea, China). Pharm: Cytotoxic (100 μg/mL: K562, InRt = 20.48%; ACHN, InRt = 16.45%; HepG2, InRt = 16.68%; A549, InRt = 1.04%). Ref: F. Song, et al, Mar. Drugs, 2012, 10, 1297 O –

O O H H

N

+

H N

N N

481 Auranomide B Type: Pyrimidines. C20H19N4O31+ Yellow oil, [α]D20 = +10.8° (c = 0.10, MeOH). Source: Marine-derived fungus Penicillium aurantiogriseum (mud, Bohai Sea, China). Pharm: Cytotoxic (100 μg/mL: K562, InRt = 76.36%; ACHN, InRt = 75.31%; HepG2, InRt = 73.28%; A549, InRt = 30.46%). Ref: F. Song, et al, Mar. Drugs, 2012, 10, 1297 O O O H H

N

+

H N

N N

482 Auranomide C Type: Pyrimidines. C19H16N4O3 Yellow oil, [α]D20 = −63.0° (c = 0.10, MeOH). Source: Marine-derived fungus Penicillium aurantiogriseum (mud, Bohai Sea, China). Pharm: Cytotoxic (100 μg/mL: K562, InRt = 5.78%; ACHN, InRt = 8.74%; HepG2, InRt = 10.72%; A549, InRt = 16.90%). Ref: F. Song, et al, Mar. Drugs, 2012, 10, 1297

https://doi.org/10.1515/9783110653908-004

178

7 Pyrimidines and Pyrazines

O N

O N H

N O NH2

483 Axistatin 1 Type: Pyrimidines. C26H41N5O Source: Sponge Agelas axifera (Koror, Republic of Palau). Pharm: Cytotoxic (various hmn and murine cancer cell lines, low μmol/L); antibacterial (potent broad-spectrum antibiotics against several gram-positive and negative bacteria). Ref: G. R. Pettit, et al, JNP, 2013, 76, 420 O

H HN N N

H H 2N

N

484 Axistatin 2 Type: Pyrimidines. C26H41N5O Source: Sponge Agelas axifera (Koror, Republic of Palau). Pharm: Cytotoxic (various hmn and murine cancer cell lines, low μmol/L); antibacterial (potent broad-spectrum antibiotics against several gram-positive and negative bacteria). Ref: G. R. Pettit, et al, JNP, 2013, 76, 420 O

H HN N N

H H 2N

N

485 Axistatin 3 Type: Pyrimidines. C29H47N5O Source: Sponge Agelas axifera (Koror, Republic of Palau). Pharm: Cytotoxic (various hmn and murine cancer cell lines, low μmol/L); antibacterial (potent broad-spectrum antibiotics against several gram-positive and negative bacteria). Ref: G. R. Pettit, et al, JNP, 2013, 76, 420

7.1 Pyrimidines

O

179

H HN N N N H

N

486 Barbital Type: Pyrimidines. C8H12N2O3 Source: Puffer fish Sphaeroides oblongus (tissues). Pharm: Hypnotic; sedative (long duration); LD50 (mus, orl) = 600 mg/kg. Ref: S. K. Mitra, et al, Chem. Comm., 1989, 16 O HN O

N H

O

487 Convolutamine J Type: Pyrimidines. C14H18Br3N2O1+ Source: Bryozoan Amathia tortuosa (Bass Strait, Tasmania, Australia). Pharm: Antitrypanosomal (Trypanosoma brucei brucei). Ref: R. A. Davis, et al, BoMC, 2011, 19, 6615 O Br

Br

N

N

+

Br

488 Crambescin A1 Type: Pyrimidines. C25H47N6O21+ [α]D20 = +8.9° (c = 0.06, MeOH). Source: Sponge Crambe crambe (Villefranche-Sur-Mer, France). Pharm: Cytotoxic. Ref: S. G. Bondu, et al, RSC Adv., 2012, 2, 2828 H + H N H N N 6

O

O

H N

NH2

6

NH

180

7 Pyrimidines and Pyrazines

489 Crambescin A2 Type: Pyrimidines. C25H47N6O21+ [α]D20 = +12.1° (c = 0.18, MeOH). Source: Sponge Crambe crambe (Villefranche-Sur-Mer, France). Pharm: Cytotoxic. Ref: S. G. Bondu, et al, RSC Adv., 2012, 2, 2828 H + H N H N N 9

O

H N

O

NH2

3

NH

490 Crambescin B Crambine B Type: Pyrimidines. C25H48N6O3 Glassy solid, [α]D = +52° (c = 0.9, MeOH). Source: Sponge Crambe crambe. Pharm: Cytotoxic (L1210); cell reaggregation inhibitor; ichthyotoxin. Ref: B. B. Snider, et al, JOC, 1993, 58, 3828│E. A. JaresErijman, et al, JNP, 1993, 56, 2186 NH2 HN

NH

O O

N H 2N

N H

O

491 Crambescin B1 Type: Pyrimidines. C25H49N6O31+ [α]D20 = −116.3° (c = 0.04, MeOH). Source: Sponge Crambe crambe (Villefranche-Sur-Mer, France). Pharm: Cytotoxic. Ref: S. G. Bondu, et al, RSC Adv., 2012, 2, 2828

7.1 Pyrimidines

181

H + H N H HN N O 6

O

H N

O

NH2

6

NH

492 Crambescin C1 Type: Pyrimidines. C25H49N6O31+ [α]D20 = +33.1° (c = 0.39, MeOH). Source: Sponge Crambe crambe (Villefranche-Sur-Mer, France). Pharm: Cytotoxic. Ref: S. G. Bondu, et al, RSC Adv., 2012, 2, 2828

HO

H + H N H HN N 6

O

O

H N

NH2

6

NH

493 Deoxy-penipanoid C 2-(4-Hydroxybenzyl) quinazolin-4(3H)-one Type: Pyrimidines. C15H12N2O2 Source: Marine-derived fungi Penicillium paneum (sediment, South China Sea) and Penicillium oxalicum 0312f1, terrestrial fungus (Isaria farinose). Pharm: Cytotoxic (A549, IC50 = 17.5 μmol/L, control Fluorouracil, IC50 = 13.7 μmol/L; Bel7402, IC50 = 19.8 μmol/ L, Fluorouracil, IC50 = 21.8 μmol/L); antibacterial (Staphylococcus aureus and Escherichia coli); antifungal (Alternaria brassicae, Fusarium oxysporium f. sp. vasinfectum, Coniella diplodiella, Physalospora piricola and Aspergillus niger); antiviral (TMV virus, EC50 = 399.57 μmol/L). Ref: S. Shen, et al, Acta Microbiol. Sinic., 2009, 49, 1240│C. -S. Li, et al, JNP, 2011, 74, 1331│C. Ma, et al, JNP, 2011, 74, 32│S. Shen, et al, Nat. Prod. Res., 2013, 27, 2286 O NH N

OH

182

7 Pyrimidines and Pyrazines

494 Didehydrocrambescin A1 Type: Pyrimidines. C25H45N6O21+ Source: Sponge Crambe crambe (Villefranche-SurMer, France). Pharm: Cytotoxic. Ref: S. G. Bondu, et al, RSC Adv., 2012, 2, 2828 NH2 N

+

N 8

O

O

H N

NH2

6

NH

495 Homocrambescin A2 Type: Pyrimidines. C26H49N6O21+ [α]D20 = +35.9° (c = 0.1, MeOH). Source: Sponge Crambe crambe (Villefranche-Sur-Mer, France). Pharm: Cytotoxic. Ref: S. G. Bondu, et al, RSC Adv., 2012, 2, 2828 H + H N H N N 10

O

O

H N

NH2

3

NH

496 Homocrambescin B1 Type: Pyrimidines. C26H51N6O31+ [α]D20 = −145.5° (c = 0.07, MeOH). Source: Sponge Crambe crambe (Villefranche-Sur-Mer, France). Pharm: Cytotoxic. Ref: S. G. Bondu, et al, RSC Adv., 2012, 2, 2828 H + H N H HN N O 6

O

O

H N

NH2

7

NH

497 Homocrambescin C1 Type: Pyrimidines. C26H51N6O31+ [α]D20 = +62.7° (c = 0.13, MeOH). Source: Sponge Crambe crambe (Villefranche-Sur-Mer, France). Pharm: Cytotoxic. Ref: S. G. Bondu, et al, RSC Adv., 2012, 2, 2828

7.1 Pyrimidines

183

H H H HO

N

+

HN

N 6

O

H N

O

NH 2

7

NH

498 Hydroxyakalone Type: Pyrimidines. C5H5N5O2 Powder. Source: Marine bacterium Agrobacterium aurantiacum N-81106. Pharm: Xanthine oxidase inhibitor. Ref: H. Izumida, et al, J. Antibiot., 1997, 50, 916 NH2

O

N NH HO

N

N H

499 Meridianin A Psammopemmin A Type: Pyrimidines. C12H10N4O Yellow needles (MeOH aq), mp 164–168 °C. Source: Sponge Psammopemma sp, ascidians Aplidium meridianum (depth of 100 m, near South Georgia I.) and Synoicum sp. (Palmer Station, Antarctica). Pharm: Protein kinases inhibitor (CDK1/cyclin B, IC50 = 2.50 μmol/L, control Rescovitine, IC50 = 0.45 μmol/L; CDK5/p25, IC50 = 3.00 μmol/L, Rescovitine, IC50 = 0.16 μmol/L; PKA, IC50 = 11.0 μmol/L, Rescovitine, IC50 > 1000 μmol/L; PKG, IC50 = 200.0 μmol/L, Rescovitine, IC50 > 1000 μmol/L; GSK3-β, IC50 = 1.30 μmol/L, Rescovitine, IC50 = 130.0 μmol/L; to prevent cell proliferation and induce cell apoptosis). Ref: M. S. Butler, et al, Aust. J. Chem., 1992, 45, 1871│L. H. Franco, et al, JNP, 1998, 61, 1130│ M. Gompel, et al, BoMCL, 2004, 14, 1703│ M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)│ M. D. Lebar, et al, Aust. J. Chem., 2010, 63, 862 N NH2

OH

N

N H

500 Meridianin B Psammopemmin C Type: Pyrimidines. C12H9BrN4O Yellow powder (EtOAc), mp 190 °C (dec). Source: Sponge Psammopemma sp., ascidians Aplidium meridianum (depth of

184

7 Pyrimidines and Pyrazines

100 m, near South Georgia I.) and Synoicum sp. Pharm: Protein kinases inhibitors (CDK1/cyclin B, IC50 = 1.50 μmol/L, control Rescovitine, IC50 = 0.45 μmol/L; CDK5/ p25, IC50 = 1.00 μmol/L, Rescovitine, IC50 = 0.16 μmol/L; PKA, IC50 = 0.21 μmol/L, Rescovitine, IC50 > 1000 μmol/L; PKG, IC50 = 1.00 μmol/L, Rescovitine, IC50 > 1000 μmol/L; GSK3-β, IC50 = 0.5 μmol/L, Rescovitine, IC50 = 130.0 μmol/L; CK1, IC50 = 1.00 μmol/L, Rescovitine, IC50 = 17 μmol/L; most potent inhibitor in meridianins); cytotoxic (LMM3, IC50 = 11.4 μmol/L; P388). Ref: M. S. Butler, et al, Aust. J. Chem., 1992, 45, 1871│L. H. Franco, et al, JNP, 1998, 61, 1130│P. M. Fresneda, et al, Tet. Lett., 2000, 41, 4777│ M. Gompel, et al, BoMCL, 2004, 14, 1703│ M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) N NH2

OH

N

N H

Br

501 Meridianin C Type: Pyrimidines. C12H9BrN4 Yellow powder (MeOH aq), mp 103–106 °C. Source: Ascidians Aplidium meridianum (depth of 100 m, near South Georgia I.) and Synoicum sp. Pharm: Protein kinases inhibitor (CDK1/cyclin B, IC50 = 3.00 μmol/L, control Rescovitine, IC50 = 0.45 μmol/L; CDK5/p25, IC50 = 6.00 μmol/L, Rescovitine, IC50 = 0.16 μmol/L; PKA, IC50 = 0.70 μmol/L, Rescovitine, IC50 > 1000 μmol/L; PKG, IC50 = 0.40 μmol/L, Rescovitine, IC50 > 1000 μmol/L; GSK3-β, IC50 = 2.00 μmol/L, Rescovitine, IC50 = 130.0 μmol/L; CK1, IC50 = 30.0 μmol/L, Rescovitine, IC50 = 17 μmol/L); cytotoxic (LMM3, IC50 = 9.3 μmol/L). Ref: L. H. Franco, et al, JNP, 1998, 61, 1130│ M. Gompel, et al, BoMCL, 2004, 14, 1703│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) N Br

N 4 7

NH2

N H

502 Meridianin D Type: Pyrimidines. C12H9BrN4 Yellow powder (EtOAc/MeOH), mp 218–221 °C. Source: Ascidian Aplidium meridianum (depth of 100 m, near South Georgia I.). Pharm: Protein kinases inhibitor (CDK1/cyclin B, IC50 = 13.0 μmol/L, control Rescovitine, IC50 = 0.45 μmol/L; CDK5/p25, IC50 = 5.50 μmol/L, Rescovitine, IC50 = 0.16 μmol/L; PKA, IC50 = 1.00 μmol/L, Rescovitine, IC50 > 1000 μmol/L; PKG,

7.1 Pyrimidines

185

IC50 = 0.80 μmol/L, Rescovitine, IC50 > 1000 μmol/L; GSK3-β, IC50 = 2.50 μmol/L, Rescovitine, IC50 = 130.0 μmol/L; CK1, IC50 = 100.0 μmol/L, Rescovitine, IC50 = 17 μmol/L); cytotoxic (LMM3, IC50 = 33.9 μmol/L; P388). Ref: L. H. Franco, et al, JNP, 1998, 61, 1130│P. M. Fresneda, et al, Tet. Lett., 2000, 41, 4777│B. Jiang, et al, Heterocycles, 2000, 53, 1489│ M. Gompel, et al, BoMCL, 2004, 14, 1703│ M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) N N 4 7

NH2

N

Br

H

503 Meridianin E Psammopemmin B Type: Pyrimidines. C12H9BrN4O Yellow cryst. (MeOH aq), mp 172–175 °C. Source: Sponge Psammopemma sp. (Antarctic), ascidian Aplidium meridianum (depth of 100 m, near South Georgia I.). Pharm: 25 Protein kinases inhibitors (CDK1/cyclin B, IC50 = 0.18 μmol/L μmol/L, control Rescovitine, IC50 = 0.45 μmol/L; CDK2/cyclin A, IC50 = 0.80 μmol/L; CDK2/cyclin E, IC50 = 1.80 μmol/L; CDK4/cyclin D1, IC50 = 3.00 μmol/L; CDK5/p25, IC50 = 0.15 μmol/L; Erk1, IC50 > 100 μmol/L; Erk2, IC50 > 100 μmol/L; c-Raf, IC50 = 1–10 μmol/L; MAPKK, IC50 > 100 μmol/L; c-Jun Nterminal kinase, IC50 = 1.00 μmol/L; Casein kinase 1, IC50 = 0.40 μmol/L; Casein kinase 2, IC50 > 100 μmol/L; Protein kinase Cα, IC50 = 1.30 μmol/L; Protein kinase Cβ1, IC50 = 1.50 μmol/L; Protein kinase Cβ2, IC50 = 2.00 μmol/L; Protein kinase Cγ, IC50 = 2.00 μmol/L; Protein kinase Cδ, IC50 = 1.20 μmol/L; Protein kinase Cε, IC50 = 4.00 μmol/L; Protein kinase Cη, IC50 = 1.30 μmol/L; Protein kinase Cξ, IC50 = 4.00 μmol/L; cAMP-dependent PK, IC50 = 0.09 μmol/L; cGMP-dependent PK, IC50 = 0.60 μmol/L; GSK3-α, IC50 = 0.90 μmol/L; GSK3-β, IC50 = 2.50 μmol/L; Insulin Receptor Tyrosine Kinase, IC50 = 80.00 μmol/L; most potent inhibitor in meridianins); cytotoxic (LMM3, IC50 = 11.1 μmol/L; P388). Ref: M. S. Butler, et al, Aust. J. Chem., 1992, 45, 1871│L. H. Franco, et al, JNP, 1998, 61, 1130│P. M. Fresneda, et al, Tet. Lett., 2000, 41, 4777│ M. Gompel, et al, BoMCL, 2004, 14, 1703│ M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) N NH2

OH

N

N H Br

186

7 Pyrimidines and Pyrazines

504 Meridianin F Type: Pyrimidines. C12H8Br2N4 Yellow needles (MeOH aq), mp 175 °C. Source: Ascidian Aplidium meridianum (Psychrophilic, cold water, depth of 100 m, South Georgia I., South Atlantic). Pharm: Protein kinases inhibitor (CDK1/cyclin B, IC50 = 20.0 μmol/L, control Rescovitine, IC50 = 0.45 μmol/L; CDK5/p25, IC50 = 20.0 μmol/L, Rescovitine, IC50 = 0.16 μmol/L; PKA, IC50 = 3.20 μmol/L, Rescovitine, IC50 > 1000 μmol/L; PKG, IC50 = 0.60 μmol/L, Rescovitine, IC50 > 1000 μmol/L; GSK3-β, IC50 = 2.00 μmol/L, Rescovitine, IC50 = 130.0 μmol/L) Ref: M. Gompel, et al, BoMCL, 2004, 14, 1703│A. M. Seldes, et al, Nat. Prod. Res., 2007, 21, 555│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) N Br

N 4 7

NH2

N

Br

H

505 Meridianin G Type: Pyrimidines. C12H10N4 Yellow needles (MeOH aq), mp 215 °C (dec). Source: Ascidian Aplidium meridianum (Psychrophilic, cold water, depth of 100 m, South Georgia I., South Atlantic). Pharm: Protein kinases inhibitor (CDK1/cyclin B, IC50 = 150 μmol/L, control Rescovitine, IC50 = 0.45 μmol/L; CDK5/p25, IC50 = 140 μmol/L, Rescovitine, IC50 = 0.16 μmol/L; PKA, IC50 = 120 μmol/L, Rescovitine, IC50 > 1000 μmol/L; PKG, IC50 = 400 μmol/L, Rescovitine, IC50 > 1000 μmol/L; GSK3β, IC50 = 350 μmol/L, Rescovitine, IC50 = 130.0 μmol/L) Ref: M. Gompel, et al, BoMCL, 2004, 14, 1703│A. M. Seldes, et al, Nat. Prod. Res., 2007, 21, 555│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) N N 4 7

NH2

N H

506 N1-Methylmanzacidin C Type: Pyrimidines. C13H16BrN3O4 [α]D23 = +36.4° (c = 0.17, MeOH). Source: Sponge Axinella brevistyla (Japan waters). Pharm: Antifungal (inhibits growth of erg6 mutant of yeast Saccharomyces cerevisiae, 100 μg/disk); cytotoxic. Ref: S. Tsukamoto, et al, JNP, 2001, 64, 1576

7.1 Pyrimidines

187

OH

O Br

N H

N

5 6

O

N

O

507 Norcrambescin B1 Type: Pyrimidines. C24H47N6O31+ [α]D20 = −114.0° (c = 0.05, MeOH). Source: Sponge Crambe crambe (Villefranche-Sur-Mer, France). Pharm: Cytotoxic. Ref: S. G. Bondu, et al, RSC Adv., 2012, 2, 2828 H + H N H HN N O 6

O

H N

O

NH2

5

NH

508 Norcrambescin C1 Type: Pyrimidines. C24H47N6O31+ [α]D20 = +76.3° (c = 0.08, MeOH). Source: Sponge Crambe crambe (Villefranche-Sur-Mer, France). Pharm: Cytotoxic. Ref: S. G. Bondu, et al, RSC Adv., 2012, 2, 2828 H H H HO

HN

N

+

N 6

O

O

H N

NH2

5

NH

509 Pyrostatin B Type: Pyrimidines. C6H10N2O2 Cryst., mp 280 °C, [α]D20 = +140° (c = 1.0, MeOH). Source: Marine-derived streptomycete Streptomyces sp. SA-3501 (marine sediment). Pharm: Osmoprotective. Ref: L. Castellanos, et al, Org. Lett., 2006, 8, 4967

188

7 Pyrimidines and Pyrazines

O

OH N N H

510 3,4,5,6-Tetrahydro-6-hydroxymethyl-3,6-dimethylpyrimidine4-carboxylic acid Type: Pyrimidines. C8H14N2O3 Source: Sponge Protophlitaspongia aga (Palau, Oceania). Pharm: Antifoulant (inhibits settling of larvae of barnacle Balanus amphitrite). Ref: T. Hattori, et al, Fish. Sci., 2001, 67, 690 N

HO

N

O

OH

511 4-Amino-5-bromo-pyrrolo[2,3-d]pyrimidine Type: Pyrrolo[2,3-d]pyrimidines. C6H5BrN4 Needles (EtOH aq), mp 240–241 °C, mp 238–239 °C (dec). Source: Sponge Echinodictyum sp. Pharm: Bronchodilator; CNS activity; cardioactive. Ref: R. Kazlauskas, et al, Aust. J. Chem., 1983, 36, 165 NH2

Br

N N H

N

512 Rigidin Type: Pyrrolo[2,3-d]pyrimidines. C19H13N3O5 Purple solid, mp 300 °C. Source: Ascidian Eudistoma cf. rigida. Pharm: Calmodulin antagonist; phosphodiesterase inhibitor. Ref: J. Kobayashi, et al, Tet. Lett., 1990, 31, 4617│E. D. Edstrom, et al, JOC, 1993, 58, 403│T. Sakamoto, et al, Tet. Lett., 1994, 35, 2919 OH O H N O

N H

OH

N H

O

7.2 Pyrazines

189

7.2 Pyrazines 513 Aflatoxin Type: Pyrazine and quinoxaline alkaloids. C12H20N2O Source: Deep-sea fungus Aspergillus sp. 16-02-1 (sediment). Pharm: Cytotoxic (100 μg/mL: K562, InRt = 33.6%–43.6%, HL60, InRt = 24.1%–53.3%, HeLa, InRt = 18.8%–45.4%, BGC823, InRt = 36.2%–51.2%); antifungal. Ref: X. Chen, et al, Chin. J. Mar. Drugs, 2013, 32, 1 (in Chinese) N

N

O

H

514 Aspidostomide E Type: Pyrazine and quinoxaline alkaloids. C16H10Br5N3O2 Source: Bryozoan Aspidostoma giganteum (Patagonia). Pharm: Cytotoxic (786-0 renal cancer cells, moderate). Ref: L. P. Patiňo, et al, JNP, 2014, 77, 1170 O H N O

Br N

Br

Br Br

Br

N H

515 Botryllazine B Type: Pyrazine and quinoxaline alkaloids. C17H12N2O3 [α]D25 = 0° (c = 0.14, MeOH). Source: Ascidian Botryllus leachi (Spain). Pharm: Cytotoxic (A549, MEL28, ED50 = 5 μg/mL). Ref: R. Durán, et al, Tetrahedron, 1999, 55. 13225 N O

N OH

OH

190

7 Pyrimidines and Pyrazines

516 (R)-6-Debromohamacanthin B Type: Pyrazine and quinoxaline alkaloids. C20H15BrN4O Yellow amorphous powder, [α]D25 = −194° (c = 0.25, MeOH). Source: Sponge Spongosorites sp. Pharm: Cytotoxic (A549, ED50 = 3.71 μg/mL, control Doxorubicin, ED50 = 0.02 μg/mL; SK-OV-3, ED50 = 8.50 μg/mL, Doxorubicin, ED50 = 0.14 μg/mL; SK-MEL-2, ED50 = 7.60 μg/mL, Doxorubicin, ED50 = 0.07 μg/mL; XF498, ED50 = 8.30 μg/mL, Doxorubicin, ED50 = 0.07 μg/mL; HCT15, ED50 = 4.20 μg/mL, Doxorubicin, ED50 = 0.02 μg/mL); antibacterial (A, Streptococcus pyogenes 308A, MIC = 6.3 μg/mL, control Meropenem, MIC = 0.004 μg/mL; B, Streptococcus pyogenes 77A, MIC = 12.5 μg/ mL, Meropenem, MIC = 0.004 μg/mL; C, Streptococcus aureus SG 511, MIC = 12.5 μg/mL, Meropenem, MIC = 0.049 μg/mL; D, Streptococcus aureus 285, MIC = 12.5 μg/mL, Meropenem, MIC = 0.098 μg/mL; E, Streptococcus aureus 503, MIC = 12.5 μg/mL, Meropenem, MIC = 0.049 μg/mL; F, Escherichia coli DC 2, MIC = 25 μg/mL, Meropenem, MIC = 0.013 μg/mL; G, Pseudomonas aeruginosa 1592E, MIC > 25 μg/mL; H, Pseudomonas aeruginosa 1771, MIC = 25 μg/mL; I, Pseudomonas aeruginosa 1771M, MIC > 25 μg/mL; J, Klebsiella oxytoca 1082 E, MIC > 25 μg/mL). Ref: B. Bao, et al, JNP, 2005, 68, 711; 2007, 70, 2 1

H N

O

5R 3''

N 3'

N H

N H

517 (R)-6″-Debromohamacanthin B Type: Pyrazine and quinoxaline alkaloids. C20H15BrN4O Yellow amorphous powder, [α]D25 = −83° (c = 0.5, MeOH). Source: Sponge Spongosorites sp. Pharm: Cytotoxic (A549, ED50 = 7.86 μg/mL, control Doxorubicin, ED50 = 0.02 μg/mL; SK-OV-3, ED50 = 7.85 μg/mL, Doxorubicin, ED50 = 0.14 μg/mL; SK-MEL-2, ED50 = 7.71 μg/mL, Doxorubicin, ED50 = 0.03 μg/mL; XF498, ED50 = 9.21 μg/mL, Doxorubicin, ED50 = 0.04 μg/mL; HCT15, ED50 = 6.31 μg/mL, Doxorubicin, ED50 = 0.10 μg/mL). Ref: B. Bao, et al, JNP, 2005, 68, 711; 2007, 70, 2 1

H N

O Br

5R 3''

N 3'

N H

N H

7.2 Pyrazines

191

518 (3S,5R)-6’,6’’Didebromo-3,4-dihydrohamacanthin B Type: Pyrazine and quinoxaline alkaloids. C20H18N4O Yellow amorphous powder, [α]D25 = +127° (c = 0.08, MeOH). Source: Sponge Spongosorites sp. Pharm: Cytotoxic (A549, ED50 > 10.00 μg/mL, control Doxorubicin, ED50 = 0.04 μg/mL; SK-OV-3, ED50 = 9.64 μg/mL, Doxorubicin, ED50 = 0.05 μg/mL; SK-MEL-2, ED50 > 10.00 μg/ mL; XF498, ED50 > 10.00 μg/mL; HCT15, ED50 > 10.00 μg/mL). Ref: B. Bao, et al, JNP, 2005, 68, 711; 2007, 70, 2 1

H N

O 3S 3'

5R

N

3''

N H

N H

519 (S)-6’,6″-Didebromohamacanthin A Type: Pyrazine and quinoxaline alkaloids. C20H16N4O Yellow amorphous powder, [α]D25 = +59° (c = 0.72, MeOH). Source: Sponge Spongosorites sp. Pharm: Cytotoxic (A549, ED50 = 8.30 μg/mL, control Doxorubicin, ED50 = 0.02 μg/mL; SK-OV-3, ED50 = 11.50 μg/mL, Doxorubicin, ED50 = 0.14 μg/mL; SK-MEL-2, ED50 = 5.00 μg/mL, Doxorubicin, ED50 = 0.07 μg/mL; XF498, ED50 = 17.10 μg/mL, Doxorubicin, ED50 = 0.07 μg/mL; HCT15, ED50 = 4.10 μg/mL, Doxorubicin, ED50 = 0.02 μg/mL); antibacterial (A, Streptococcus pyogenes 308A, MIC = 25 μg/mL, control Meropenem, MIC = 0.004 μg/mL; B, Streptococcus pyogenes 77A, MIC = 25 μg/mL; C, Streptococcus aureus SG 511, MIC > 25 μg/mL; D, Streptococcus aureus 285, MIC > 25 μg/mL; E, Streptococcus aureus 503, MIC > 25 μg/mL; F, Escherichia coli DC 2, MIC > 25 μg/ mL; G, Pseudomonas aeruginosa 1592E, MIC = 25 μg/mL; H, Pseudomonas aeruginosa 1771, MIC = 25 μg/mL; I, Pseudomonas aeruginosa 1771M, MIC > 25 μg/mL; J, Klebsiella oxytoca 1082E, MIC > 25 μg/mL). Ref: B. Bao, et al, JNP, 2005, 68, 711; 2007, 70, 2 H N

1

H N

O

3'' 6S

3'

N H

N

192

7 Pyrimidines and Pyrazines

520 (R)-6’,6″-Didebromohamacanthin B Type: Pyrazine and quinoxaline alkaloids. C20H16N4O Yellow amorphous powder, [α]D25 = −288° (c = 0.4, MeOH). Source: Sponge Spongosorites sp. Pharm: Cytotoxic (A549, ED50 = 11.70 μg/mL, control Doxorubicin, ED50 = 0.02 μg/mL; SKOV-3, ED50 = 12.60 μg/mL, Doxorubicin, ED50 = 0.14 μg/mL; SK-MEL-2, ED50 = 13.70 μg/mL, Doxorubicin, ED50 = 0.07 μg/mL; XF498, ED50 = 24.10 μg/mL, Doxorubicin, ED50 = 0.07 μg/mL; HCT15, ED50 = 4.79 μg/mL, Doxorubicin, ED50 = 0.02 μg/mL); antibacterial (A, Streptococcus pyogenes 308A, MIC > 25 μg/mL, control Meropenem, MIC = 0.004 μg/mL; B, Streptococcus pyogenes 77A, MIC > 25 μg/ mL; C, Streptococcus aureus SG 511, MIC > 25 μg/mL; D, Streptococcus aureus 285, MIC > 25 μg/mL; E, Streptococcus aureus 503, MIC > 25 μg/mL; F, Escherichia coli DC 2, MIC > 25 μg/mL; G, Pseudomonas aeruginosa 1592E, MIC = 25 μg/mL; H, Pseudomonas aeruginosa 1771, MIC = 25 μg/mL; I, Pseudomonas aeruginosa 1771M, MIC > 25 μg/mL; J, Klebsiella oxytoca 1082E, MIC > 25 μg/mL). Ref: B. Bao, et al, JNP, 2005, 68, 711; 2007, 70, 2 1

H N

O

5R 3''

N 3'

N H

N H

521 Dragmacidin Biemnidin Type: Pyrazine and quinoxaline alkaloids. C21H19Br3N4O Powder, [α]D20 = −3° (c = 13.2, Me2CO). Source: Sponge Dragmacidon sp. Pharm: Cytotoxic (P388, IC50 = 15 μg/mL; DAMB, IC50 = 1–10 μg/mL; inhibits growth of A549). Ref: C. R. Whitlock, et al, Tet. Lett., 1994, 35, 371│B. Jiang, et al, JOC, 1994, 59, 6823 H N

Br

H N

OH

H

H N

Br Br

N H

522 Dragmacidin E Type: Pyrazine and quinoxaline alkaloids. C25H20BrN7O2 Yellow solid, [α]D = −34° (c = 0.9, EtOH). Source: Sponge Spongosorites sp. (deep water, Australia). Pharm: Serine threonine protein phosphatase inhibitor. Ref: R. J. Capon, et al, JNP, 1998, 61, 660

7.2 Pyrazines

H N

NH2

H N

N

Br N

N

HO

193

OH

N H

523 (S)-Hamacanthin A Type: Pyrazine and quinoxaline alkaloids. C20H14Br2N4O Pale yellow powder, [α]D24 = +84° (c = 0.1, MeOH). Source: Sponge Hamacantha sp. (deep water). Pharm: Antifungal (Candida albicans and Cryptococcus neoformans); antibacterial (Bacillus subtilis). Ref: S. P. Gunasekera, et al, JNP, 1994, 57, 1437 H N O

H N

Br

S

H N Br

N H

524 (S)-Hamacanthin B Type: Pyrazine and quinoxaline alkaloids. C20H14Br2N4O Pale yellow powder, [α]D24 = +172° (c = 0.1, MeOH). Source: Sponge Hamacantha sp. (deep water). Pharm: Antifungal (Candida albicans and Cryptococcus neoformans); antibacterial (Bacillus subtilis). Ref: S. P. Gunasekera, et al, JNP, 1994, 57, 1437

O

H N H N

Br

N H

S

N H

Br

525 (11S)-Hydroxyl aspergillic acid Type: Pyrazine and quinoxaline alkaloids. C12H20N2O3 Source: Deep-sea fungus Aspergillus sp. 16-02-1 (sediment). Pharm: Cytotoxic (100 μg/mL: K562, InRt = 33.6%–43.6%, HL60, InRt = 24.1%–53.3%, HeLa, InRt = 18.8%–45.4%, BGC823, InRt = 36.2%–51.2%); antifungal. Ref: X. Chen, et al, Chin. J. Mar. Drugs, 2013, 32, 1 (in Chinese)

194

7 Pyrimidines and Pyrazines

N

N

O

OH

OH

526 Hyrtioseragamine A Type: Pyrazine and quinoxaline alkaloids. C16H18N6O2 Yellow amorph. solid. Source: Sponge Hyrtios sp. (Seragaki, Okinawa). Pharm: Antifungal (Aspergillus niger, MIC = 8.33 μg/mL, Cryptococcus neoformans, MIC = 33.3 μg/mL). Ref: Y. Takahashi, et al, Org. Lett., 2011, 13, 628

H N NH2

NH2

H N

O

NH N

O

527 Hyrtioseragamine B Type: Pyrazine and quinoxaline alkaloids. C26H24N8O3 Yellow amorph. solid. Source: Sponge Hyrtios sp. (Seragaki, Okinawa). Pharm: Antifungal (Aspergillus niger, MIC = 16.6 μg/mL, Cryptococcus neoformans, MIC = 16.6 μg/mL). Ref: Y. Takahashi, et al, Org. Lett., 2011, 13, 628

H N

N H 2N

O

H N

NH2 NH

NH O

N O

528 Kasarin Type: Pyrazine and quinoxaline alkaloids. C15H23N3O5 Oil, [α]D26 = +22° (c = 0.3, CHCl3). Source: Marine-derived fungus Hyphomycetes sp. from zoanthid Zoanthus sp. Pharm: Antibacterial (weak). Ref: M. Kita, et al, Tet. Lett., 2007, 48, 8628│K. Suenaga, et al, Heterocycles, 2000, 52, 1033

7.2 Pyrazines

O

195

O NH2

O

N N

O

O

529 Maedamine A Ma’edamine A Type: Pyrazine and quinoxaline alkaloids. C23H24Br3N3O3 Amorph. yellow solid. Source: Sponge Suberea sp. (Okinawa). Pharm: Kinase c-erbB-2 inhibitor (IC50 = 6.7 μg/mL); cytotoxic (L1210, IC50 = 4.3 μg/mL; KB, IC50 = 5.2 μg/mL). Ref: K. Hirano, et al, Tetrahedron, 2000, 56, 8107│ M. Tsuda, et al, JNP, 2001, 64, 980│D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) Br N

O N

Br

N

Br O

O

H

530 Maedamine B Type: Pyrazine and quinoxaline alkaloids. C22H22Br3N3O3 Amorph. yellow solid. Source: Sponge Suberea sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 3.9 μg/mL; KB, IC50 = 4.5 μg/mL). Ref: K. Hirano, et al, Tetrahedron, 2000, 56, 8107│ M. Tsuda, et al, JNP, 2001, 64, 980

H N

Br O

Br

N

N

Br

O

O

H

531 New Aspergillic acid Type: Pyrazine and quinoxaline alkaloids. C12H20N2O2 Source: Deep-sea fungus Aspergillus sp. 16-02-1 (sediment). Pharm: Cytotoxic (100 μg/mL: K562, InRt = 33.6%– 43.6%, HL60, InRt = 24.1%–53.3%, HeLa, InRt = 18.8%–45.4%, BGC823, InRt = 36.2%–51.2%); antifungal. Ref: X. Chen, et al, Chin. J. Mar. Drugs, 2013, 32, 1 (in Chinese)

196

7 Pyrimidines and Pyrazines

N

N

O

OH

532 Ritterazine A Type: Pyrazine and quinoxaline alkaloids. C54H76N2O10 Glassy solid, [α]D = +112.0° (c 0.1, MeOH). Source: Ascidian Ritterella tokioka (Japan waters). Pharm: Cytotoxic (P388, IC50 = 3.5 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484 O H

HO

OH

H O

H

N

22R

H

O

H

O

HO

OH

O

H N H

OH

533 Ritterazine B Type: Pyrazine and quinoxaline alkaloids. C54H78N2O9 [α]D = +43.0° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 0.15 ng/mL; highly promising drug candidate). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484

O

OH

H

12

HO

H

7'

H H

H N O O HO HO

H

O

14

N H

22R

15

H

17'

OH

534 Ritterazine C Type: Pyrazine and quinoxaline alkaloids. C54H78N2O9 Glassy solid, [α]D = +72.0° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 92 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484│S. Fukuzawa, et al, JOC, 1995, 60, 608

7.2 Pyrazines

O

OH

O

N

HO

H

H

H N O

H

H

H

197

H

H HO OH

O OH

535 Ritterazine D Type: Pyrazine and quinoxaline alkaloids. C54H76N2O10 Glassy solid, [α]D = +81.4° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 16 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484│S. Fukuzawa, et al, Tetrahedron, 1995, 51, 6707 O H

HO

O HO

N

O 22S

O

H N

H OH

H

H

H O

OH

H

OH

536 Ritterazine E 24-Methylritterazine D Type: Pyrazine and quinoxaline alkaloids. C55H78N2O10 Glassy solid, [α]D = +70.8° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 3.5 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484│S. Fukuzawa, et al, Tetrahedron, 1995, 51, 6707 O H

HO

N

O HO

H OH

OH

H O

H

22

H O

OH

H N H

O

198

7 Pyrimidines and Pyrazines

537 Ritterazine F Type: Pyrazine and quinoxaline alkaloids. C54H78N2O9 Glassy solid, [α]D = +59.0° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 0.73 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484│S. Fukuzawa, et al, Tetrahedron, 1995, 51, 6707

O

OH

H

12

HO

H

7'

H H

H N O O HO

H

O

14

N

22S

15

H

H

17'

HO

OH

538 Ritterazine G Type: Pyrazine and quinoxaline alkaloids. C54H76N2O9 Glassy solid, [α]D = +91.4° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 0.73 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1995, 60, 608│S. Fukuzawa, et al, Tetrahedron, 1995, 51, 6707

OH

O H

12

HO

H

7'

H N H

H N O O HO HO

H

22

O

14 15

H

17'

OH

539 Ritterazine H Type: Pyrazine and quinoxaline alkaloids. C54H76N2O9 Glassy solid, [α]D = +96.0° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 16 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484│S. Fukuzawa, et al, Tetrahedron, 1995, 51, 6707

7.2 Pyrazines

O

O

H

12

HO

H

7'

H H N

O O HO

H

22

O

14

N

H

199

15

H

H

17'

HO

OH

540 Ritterazine I Type: Pyrazine and quinoxaline alkaloids. C54H76N2O10 Glassy solid, [α]D = +74.5° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 14 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484│S. Fukuzawa, et al, Tetrahedron, 1995, 51, 6707

O

O H

12

HO

H

7'

H N H

H N O O HO

H

O

14

OH

22

15

H

17'

HO

OH

541 Ritterazine J Type: Pyrazine and quinoxaline alkaloids. C54H76N2O11 Glassy solid, [α]D = +66.1° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 13 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484│S. Fukuzawa, et al, Tetrahedron, 1995, 51, 6707 OH HO

HO

H

7'

H

N H

H

O

H

O HO

OH HO

N

H

O OH O

200

7 Pyrimidines and Pyrazines

542 Ritterazine K Type: Pyrazine and quinoxaline alkaloids. C54H76N2O10 Glassy solid, [α]D = +74.0° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 9.5 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484│S. Fukuzawa, et al, Tetrahedron, 1995, 51, 6707

OH HO H

7'

H

N

N

H

O

OH O

H

H

O

17

O

H

HO OH

HO

543 Ritterazine L Type: Pyrazine and quinoxaline alkaloids. C54H76N2O9 Glassy solid, [α]D = +85.5° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 10 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484│S. Fukuzawa, et al, Tetrahedron, 1995, 51, 6707

OH

H

7'

H

N

H

O

17

O OH O

H

H

O

H

N

H

HO OH

HO

544 Ritterazine M Type: Pyrazine and quinoxaline alkaloids. C54H76N2O9 Glassy solid, [α]D = +95.1° (c = 0.1, MeOH). Source: Ascidian Ritterella tokioka [Syn. Ritterella pedunculata]. Pharm: Cytotoxic (P388, IC50 = 15 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484│S. Fukuzawa, et al, Tetrahedron, 1995, 51, 6707

7.2 Pyrazines

OH

H

7'

O

OH O

H

H N

H

O

O

H 17

H

N

201

H

HO OH

HO

545 Ritterazine N Type: Pyrazine and quinoxaline alkaloids. C54H76N2O8 [α]D = +121.7° (c = 0.05, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 0.46 μg/ mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484 O H H O H

O HO

O

H

N

H

22'R

O

H N

H

OH H

H

H

O

546 Ritterazine O Type: Pyrazine and quinoxaline alkaloids. C54H76N2O8 [α]D = +108.6° (c = 0.1, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 2.1 μg/ mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484 O H H O O

H H

HO

H N

O

H

N

H

22'S

OH H

O H

H

O

547 Ritterazine P Type: Pyrazine and quinoxaline alkaloids. C54H78N2O7 [α]D = +42.5° (c = 0.05, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 0.71 μg/ mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484

202

7 Pyrimidines and Pyrazines

O

OH

H O

H

H N

H O

H

H

22 ' R

O

N

H H HO

H

H

O

548 Ritterazine Q Type: Pyrazine and quinoxaline alkaloids. C54H78N2O7 [α]D = +57.8° (c = 0.05, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 0.57 μg/ mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484

O

OH

H O

H

H

22 ' S

O

N

H

O

H

N

H

H

H

H

H HO

O

549 Ritterazine R Type: Pyrazine and quinoxaline alkaloids. C54H80N2O6 [α]D = +26.3° (c = 0.05, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 2.1 μg/ mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484

OH

H H

H H

O 22'R

O

H

OH

H H

O

O

H

N

N

H

H

7.2 Pyrazines

203

550 Ritterazine S Type: Pyrazine and quinoxaline alkaloids. C54H80N2O6 [α]D = +43.3° (c = 0.05, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 0.46 μg/ mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484

OH

N

H

H

H N

H

O

O

H

H H

O

H

H

22'S

H

O

OH

551 Ritterazine T Type: Pyrazine and quinoxaline alkaloids. C54H76N2O8 [α]D = +106.6° (c = 0.1, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 0.46 μg/ mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484 O H

H

N

H

O

O

H

H N

OH O H O H

H

OH OH

552 Ritterazine U Type: Pyrazine and quinoxaline alkaloids. C54H76N2O9 [α]D = +89.0° (c = 0.1, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 2.1 μg/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484

204

7 Pyrimidines and Pyrazines

O H OH

O

H

O

H N

H

HO

O

H

N

H

O

OH H

H

H

O

553 Ritterazine V Type: Pyrazine and quinoxaline alkaloids. C54H76N2O9 [α]D = +109.2° (c = 0.05, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 2.1 μg/ mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484 O H O

OH H O

H N

H O

H

HO

N

H H HO

O

H H

O

554 Ritterazine W Type: Pyrazine and quinoxaline alkaloids. C54H76N2O8 [α]D = +120.4° (c = 0.05, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 3.2 μg/ mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484 O H

OH

H O

H N

22R

H

H

O

N H

O

O

H

H

OH

OH

555 Ritterazine X Type: Pyrazine and quinoxaline alkaloids. C54H76N2O8 [α]D = +108.0° (c = 0.05, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 3.0 μg/ mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484

7.2 Pyrazines

O H

OH

H O

H

N

205

22S

O

H

H N H

H

O H

O

OH

OH

556 Ritterazine Y Type: Pyrazine and quinoxaline alkaloids. C54H78N2O7 [α]D = +57.4° (c = 0.1, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 3.5 ng/mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484

OH

H

H N

H

O

HO

O

H

N

H

O

O

H

H

H

OH

557 Ritterazine Z Type: Pyrazine and quinoxaline alkaloids. C55H78N2O9 [α]D = +105.8° (c = 0.1, CHCl3). Source: Ascidian Ritterella tokioka. Pharm: Cytotoxic (P388, IC50 = 2.0 μg/ mL). Ref: S. Fukuzawa, et al, JOC, 1997, 62, 4484 O H H HO

H

O

O O

OH

N H N

H O

H

H

H

OH

H

O H

206

7 Pyrimidines and Pyrazines

558 Tetroazolemycin A Type: Pyrazine and quinoxaline alkaloids. C34H40N6O6S4 Source: Marine-derived streptomycete Streptomyces olivaceus (deep water, southwest Indian Ocean). Pharm: Binding affinity (for metal ions Fe3+, Cu2+ and Zn2+). Ref: N. Liu, et al, Mar. Drugs, 2013, 11, 1524 O OH

O

N N

H

S

N N

S S

S

H

N

H

N O

OH

O

559 Tetroazolemycin B Type: Pyrazine and quinoxaline alkaloids. C34H40N6O6S4 Source: Marine-derived streptomycete Streptomyces olivaceus (deep water, southwest Indian Ocean). Pharm: Binding affinity (for metal ions Fe3+, Cu2+ and Zn2+). Ref: N. Liu, et al, Mar. Drugs, 2013, 11, 1524 O OH

O

N N

H

S

N N

S S

S

H

N

H

N O

OH

O

560 Hanishin racemic methyl ester Type: Pyrrolo[1,2-α]pyrazines. C10H10Br2N2O3 [α]D25 = 0° (c = 0.95, MeOH). Source: Sponge Homaxinella sp. (deep water, Japan). Pharm: Cytotoxic (P388, ED50 = 30 μg/ mL). Ref: I. Mancini, et al, Tet. Lett., 1997, 38, 6271│A. Umeyama, et al, JNP, 1998, 61, 1433 O N

Br N Br

O O

7.2 Pyrazines

207

561 (S)-Longamide A Type: Pyrrolo[1,2-α]pyrazines. C7H6Br2N2O2 [α]D = +86° (c = 0.001, MeOH). Source: Sponges Agelas longissima, Agelas dispar and Acanthella carteri. Pharm: Antibacterial (gram-positive and -negative bacteria, MIC = 60 μg/mL). Ref: F. Cafieri, et al, Tet. Lett., 1995, 36, 7893│F. Cafieri, et al, JNP, 1998, 61,122│I. Mancini, et al, Tet. Lett., 1997, 38, 6271 Br Br

O N NH

HO

S

562 Longamide B Type: Pyrrolo[1,2-α]pyrazines. C9H8Br2N2O3 Amorph. solid, [α]D25 = 0° (c = 0.004, MeOH). Source: Sponges Agelas dispar (Caribbean Sea), Agelas longissima and Acanthella carteri. Pharm: Antibacterial (Mueller-Hinton agar test, gram-positive bacteria: Bacillus subtilis ATCC 6633, MIC = 45 μg/mL; Staphylococcus aureus ATCC6538, MIC = 55 μg/mL) (Cafieri, 1998). Ref: F. Cafieri, et al, Tet. Lett., 1995, 36,7893│F. Cafieri, et al, JNP, 1998, 61,122│I. Mancini, et al, Tet. Lett., 1997, 38, 6271 O NH

Br N Br

OH O

563 Phakellin Type: Pyrrolo[1,2-α]pyrazines. C11H11Br2N5O2 Source: Sponge Agelas sp. Pharm: Antibacterial (Staphylococcus epidermidis, MIC > 51 μmol/L). Ref: T. Hertiani, et al, BoMC, 2010, 18, 1297 NH2 HN Br

Br

N

HO N

N O

208

7 Pyrimidines and Pyrazines

564 2-Bromolavanducyanin Type: Phenazine alkaloids. C22H23BrN2O Source: Marine-derived streptomycete Streptomyces sp. (source unspecified). Pharm: LPS-induced NO production inhibitor (RAW 264.7 cells, IC50 > 48.6 μmol/L, control Resveratrol, IC50 = (31.9 ± 1.8)μmol/L); PGE2 production inhibitor (RAW 264.7 cells, IC50 = (7.5 ± 2.03)μmol/L, Resveratrol, IC50 = (2.5 ± 0.43)μmol/L, possibly due to inhibition of cyclooxygenases in addition to the expression of COX-2); COX inhibitor (ovine COX-1, IC50 = (11.0 ± 0.53)μmol/L, control Indomethacin, IC50 = (0.42 ± 0.21)μmol/L; hmn COX-2, IC50 = (4.0 ± 0.41) μmol/L, control Celecoxib, IC50 = (0.05 ± 0.03)μmol/L; selectivity COX-1/COX-2, 2.75). Ref: T. P. Kondratyuk, et al, Mar. Drugs, 2012, 10, 451 O N

Br

N

565 2-Bromo-5-(2-methyl-2-butylene)phenazinone Type: Phenazine alkaloids. C17H15BrN2O Source: Marine-derived streptomycete Streptomyces sp. (source unspecified). Pharm: LPS-induced NO production inhibitor (RAW 264.7 cells, IC50 = (15.1 ± 2.7)μmol/L, control Resveratrol, IC50 = (31.9 ± 1.8) μmol/L); PGE2 production inhibitor (RAW 264.7 cells, IC50 = (0.89 ± 0.22)μmol/L Resveratrol, IC50 = (2.5 ± 0.43)μmol/L, possibly due to inhibition of cyclooxygenases in addition to the expression of COX-2); COX inhibitor (ovine COX-1, IC50 = (5.6 ± 0.61) μmol/L, control Indomethacin, IC50 = (0.42 ± 0.21)μmol/L; hmn COX-2, IC50 = (7.2 ± 0.13)μmol/L, control Celecoxib, IC50 = (0.05 ± 0.03)μmol/L; selectivity COX-1/ COX-2, 0.78). Ref: T. P. Kondratyuk, et al, Mar. Drugs, 2012, 10, 451 O N

Br

N

566 Dermacozine A Type: Phenazine alkaloids. C15H14N4O2 Source: Marine-derived actinomycete Dermacoccus abyssi sp. nov. (piezotolerant, depth of 10898 m, sediment, Mariana Trench, Pacific Ocean). Pharm: Cytotoxic (K562, IC50 = 140 μmol/L); antioxidant

7.2 Pyrazines

209

(DPPH scavenger, IC50 = 77.5 μmol/L, control Ascorbic acid, IC50 = 12.1 μmol/L). Ref: W. M. Abdel-Mageed, et al, Org. Biomol. Chem., 2010, 8, 2352 O

NH2

N

N H H 2N

O

567 Dermacozine B Type: Phenazine alkaloids. C22H18N4O3 Source: Marine-derived actinomycete Dermacoccus abyssi sp. nov. (piezotolerant, depth of 10898 m, sediment, Mariana Trench, Pacific Ocean). Pharm: Cytotoxic (K562, IC50 = 220 μmol/L); antioxidant (DPPH scavenger, IC50 = 38.0 μmol/L, control Ascorbic acid, IC50 = 12.1 μmol/L). Ref: W. M. Abdel-Mageed, et al, Org. Biomol. Chem., 2010, 8, 2352 O

O

NH2

N

N H H 2N

O

568 Dermacozine C Type: Phenazine alkaloids. C22H17N3O4 Source: Marine-derived actinomycete Dermacoccus abyssi sp. nov. (piezotolerant, depth of 10898 m, sediment, Mariana Trench, Pacific Ocean). Pharm: Cytotoxic (K562, IC50 = 180 μmol/L); antioxidant (DPPH scavenger, IC50 = 8.4 μmol/L, more potent than control, control Ascorbic acid, IC50 = 12.1 μmol/L). Ref: W. M. Abdel-Mageed, et al, Org. Biomol. Chem., 2010, 8, 2352 O

O

NH2

N

N H HO

O

569 Dermacozine D Type: Phenazine alkaloids. C24H19N3O5 Source: Marine-derived actinomycete Dermacoccus abyssi sp. nov. (piezotolerant, depth of 10898 m, sediment, Mariana

210

7 Pyrimidines and Pyrazines

Trench, Pacific Ocean). Pharm: Cytotoxic (K562, IC50 = 100 μmol/L); antioxidant (DPPH scavenger, IC50 = 106.9 μmol/L, control Ascorbic acid, IC50 = 12.1 μmol/L). Ref: W. M. Abdel-Mageed, et al, Org. Biomol. Chem., 2010, 8, 2352 O

O O O

N

N H H 2N

O

570 Dermacozine E Type: Phenazine alkaloids. C23H16N4O3 Source: Marine-derived actinomycete Dermacoccus abyssi sp. nov. (piezotolerant, depth of 10898 m, sediment, Mariana Trench, Pacific Ocean). Pharm: Cytotoxic (K562, IC50 = 145 μmol/L). Ref: W. M. AbdelMageed, et al, Org. Biomol. Chem., 2010, 8, 2352

O

H N

O

N

N H 2N

O

571 Dermacozine F Type: Phenazine alkaloids. C23H15N3O4 Source: Marine-derived actinomycete Dermacoccus abyssi sp. nov. (piezotolerant, depth of 10898 m, sediment, Mariana Trench, Pacific Ocean). Pharm: Cytotoxic (K562, IC50 = 9 μmol/L, moderate). Ref: W. M. Abdel-Mageed, et al, Org. Biomol. Chem., 2010, 8, 2352 O

O

O

N

N H 2N

O

572 Dermacozine G Type: Phenazine alkaloids. C23H15N3O5 Source: Marine-derived actinomycete Dermacoccus abyssi sp. nov. (piezotolerant, depth of 10898 m, sediment, Mariana Trench, Pacific Ocean). Pharm: Cytotoxic (K562, IC50 = 7 μmol/L, moderate). Ref: W. M. Abdel-Mageed, et al, Org. Biomol. Chem., 2010, 8, 2352

7.2 Pyrazines

O

O

211

O

N

N

OH

O

H 2N

573 5,10-Dihydrophencomycin methyl ester Type: Phenazine alkaloids. C16H14N2O4 Orange needles (CHCl3/MeOH), mp 231 °C. Source: Marine-derived streptomycete Streptomyces sp. B8251 from marine sediment sample (Gulf of Mexico). Pharm: Antimicrobial. Ref: K. Puseker, et al, J. Antibiot., 1997, 50, 479 O

O H N

N H O

O

574 Geranylphenazinediol Type: Phenazine alkaloids. C22H24N2O2 Source: Marine-derived streptomycete Streptomyces sp. (sediment, Kiel Fjord, Baltic Sea). Pharm: Acetylcholinesterase inhibitor. Ref: B. Ohlendorf, et al, JNP, 2012, 75, 1400

OH N

N OH

575 Griseoluteic acid Type: Phenazine alkaloids. C15H12N2O4 Orange cryst. Source: Marine bacterium Pelagiobacter variabilis (gram-negative) from macro alga Pocockiella variegata (Palau, Oceania), marine bacterium LL-14I352 (halophilic) from an unidentified ascidian (orange, Fiji). Pharm: DNA damaging agent. Ref: K. Yagishita, J. Antibiot., Ser. A, 1960, 13, 83│N. Imamura, et al, J. Antibiot., 1997, 50, 8│ M. P. Singh, et al, J. Antibiot., 1997, 50, 785

212

7 Pyrimidines and Pyrazines

COOH

O N 9

N OH

576 6-(Hydroxymethyl)-1-phenazinecarboxamide Type: Phenazine alkaloids. C14H11N3O2 Yellow powder. Source: Marine-derived bacterium Brevibacterium sp. KMD 003 from sponge Callyspongia sp. (purple vase sponge, Kyung-Po, R. O. Korea). Pharm: Antibacterial (Enterococcus hirae and Micrococcus luteus, MIC = 5 μmol/L). Ref: E. J. Choi, et al, J. Antibiot., 2009, 62, 621 O

NH2

N

N HO

577 Lavanducyanin Type: Phenazine alkaloids. C22H24N2O Deep blue prisms (MeOH/Et2O), mp 161–162 °C, mp 135–136 °C. Source: Marine-derived streptomycetes Streptomyces spp. Pharm: LPSinduced NO production inhibitor (RAW 264.7 cells, IC50 = (8.0 ± 0.39)μmol/L, control Resveratrol, IC50 = (31.9 ± 1.8)μmol/L); PGE2 production inhibitor (RAW 264.7 cells, IC50 = (0.63 ± 0.16)μmol/L Resveratrol, IC50 = (2.5 ± 0.43)μmol/L, possibly due to inhibition of cyclooxygenases in addition to the expression of COX-2); COX inhibitor (ovine COX-1, IC50 = (30.0 ± 1.08)μmol/L, control Indomethacin, IC50 = (0.42 ± 0.21)μmol/L; hmn COX-2, IC50 = (34.0 ± 1.1)μmol/L, control Celecoxib, IC50 = (0.05 ± 0.03)μmol/L; selectivity COX-1/COX-2, 0.88); cytotoxic; testosterone 5α-reductase inhibitor. Ref: Imai, H. et al, J. Antibiot., 1989, 42, 1196│Nakayama, O. et al, J. Antibiot., 1989, 42, 1221; 1230; 1235│Imai, S. et al, J. Antibiot., 1993, 46, 1232│T. P. Kondratyuk, et al, Mar. Drugs, 2012, 10, 451 O N

N

7.2 Pyrazines

213

578 Pelagiomicin A Type: Phenazine alkaloids. C20H21N3O6 Red-orange needles, mp 130 °C (dec), [α]D20 = +19.8° (c = 1, CHCl3). Source: Marine bacterium Pelagiobacter variabilis (gram-negative) from macro alga Pocockiella variegata (Palau, Oceania); marine bacterium LL-14I352 (halophilic) from an unidentified ascidian (orange, Fiji). Pharm: Cytotoxic; antibiotic; DNA damaging agent. Ref: K. Yagishita, J. Antibiot., Ser. A, 1960, 13, 83│N. Imamura, et al, J. Antibiot., 1997, 50, 8│ M. P. Singh, et al, J. Antibiot., 1997, 50, 785 HO

O

O

N N O H 2N

O OH

579 Pelagiomicin B Type: Phenazine alkaloids. C20H21N3O5 Red-orange needles. Source: Marine bacterium Pelagiobacter variabilis (gram-negative) from macro alga Pocockiella variegata (Palau, Oceania). Pharm: Cytotoxic; antibiotic. Ref: K. Yagishita, J. Antibiot., Ser. A, 1960, 13, 83│N. Imamura, et al, J. Antibiot., 1997, 50, 8│ M. P. Singh, et al, J. Antibiot., 1997, 50, 785 HO

O

O

N N O H 2N

O

580 Pelagiomicin C Type: Phenazine alkaloids. C17H15N3O5 Red-orange solid. Source: Marine bacterium Pelagiobacter variabilis (gram-negative) from macro alga Pocockiella variegata (Palau, Oceania). Pharm: Cytotoxic; antibiotic; antibacterial (gram-positive and negative bacteria). Ref: K. Yagishita, J. Antibiot., Ser. A, 1960, 13, 83│N. Imamura, et al, J. Antibiot., 1997, 50, 8│ M. P. Singh, et al, J. Antibiot., 1997, 50, 785

214

7 Pyrimidines and Pyrazines

OH

O

O N N O H 2N

O

581 Phenazine Alkaloid 1 3’-L-Quinovosyl saphenate Type: Phenazine alkaloids. C21H22N2O7 Amorphous yellow solid, [α]D = −40° (c = 0.73, MeOH). Source: Marine-derived streptomycete Streptomyces sp. CNB-253 (Bodega Bay, California, shallow sediments). Pharm: Antibacterial (Hemophilus influenzae, MIC = 1.0 μg/mL; Clostridium perfringens, MIC = 4.0 μg/mL). Ref: C. Pathirana, et al, JOC, 1992, 57, 740 OH N

N O

H O

HO O

H O OH

582 Phenazine Alkaloid 2 2’-L-Quinovosyl saphenate Type: Phenazine alkaloids. C21H22N2O7 Amorphous yellow solid, [α]D = −35° (c = 0.49, MeOH). Source: Marine-derived streptomycete Streptomyces sp. CNB-253 (Bodega Bay, California, shallow sediments). Pharm: Antibacterial (Escherichia coli, MIC = 4.0 μg/mL; Salmonella enteritidis, MIC = 4.0 μg/ mL; Clostridium perfringens, MIC = 4.0 μg/mL). Ref: C. Pathirana, et al, JOC, 1992, 57, 740 OH N

N O

H O

O

HO HO

OH

7.2 Pyrazines

215

583 Phenazine Alkaloid 3 Type: Phenazine alkaloids. C21H22N2O7 Source: Marine-derived streptomycete Streptomyces sp. CNB-253 (Bodega Bay, California, shallow sediments). Pharm: Antimicrobial (moderate). Ref: C. Pathirana, et al, JOC, 1992, 57, 740 OH N

N O

OH O

O HO

H OH

584 Phenazine Alkaloid 4 Type: Phenazine alkaloids. C21H22N2O7 Source: Marine-derived streptomycete Streptomyces sp. CNB-253 (Bodega Bay, California, shallow sediments). Pharm: Antimicrobial (moderate). Ref: C. Pathirana, et al, JOC, 1992, 57, 740 OH N

N

OH

HO O

O

O H

OH

585 1,6-Phenazinedimethanol Type: Phenazine alkaloids. C14H12N2O2 Yellow powder. Source: Marine-derived bacterium Brevibacterium sp. KMD 003 from sponge Callyspongia sp. (purple vase sponge, Kyung-Po, R. O. Korea). Pharm: Antibacterial (Enterococcus hirae and Micrococcus luteus, MIC = 5 μmol/L). Ref: E. J. Choi, et al, J. Antibiot., 2009, 62, 621 OH N

N HO

216

7 Pyrimidines and Pyrazines

586 Streptophenazine A Type: Phenazine alkaloids. C24H28N2O5 Amorph. yellow solid, [α]D20 = −50° (c = 0.1, MeOH). Source: Marine-derived streptomycete Streptomyces sp. HB202. Pharm: Antibacterial (Bacillus subtilis, 46.9 μg/mL; Staphylococcus lentus, 62.5 μg/mL). Ref: M. I. Mitova, et al, JNP, 2008, 71, 824 O

OH

O

6'

N 6

N O

O

587 Streptophenazine B Type: Phenazine alkaloids. C24H28N2O5 Amorph. yellow solid, [α]D20 = −45° (c = 0.1, MeOH). Source: Marine-derived streptomycete Streptomyces sp. HB202. Pharm: Antibacterial (Staphylococcus lentus, 62.5 μg/mL). Ref: M. I. Mitova, et al, JNP, 2008, 71, 824 O

OH

O

6'

N 6

N O

O

588 Streptophenazine C Type: Phenazine alkaloids. C23H26N2O5 Amorph. red solid, [α]D20 = −36° (c = 0.02, MeOH). Source: Marine-derived streptomycete Streptomyces sp. HB202. Pharm: Antibacterial (Bacillus subtilis, 15.6 μg/mL; Staphylococcus lentus, 46.9 μg/mL). Ref: M. I. Mitova, et al, JNP, 2008, 71, 824 O O N 6

N O

OH

OH 6'

7.2 Pyrazines

217

589 Streptophenazine D Type: Phenazine alkaloids. C23H26N2O5 Amorph. yellow solid, [α]D20 = −41° (c = 0.02, MeOH). Source: Marine-derived streptomycete Streptomyces sp. HB202. Pharm: Antibacterial (Bacillus subtilis, 62.5 μg/mL). Ref: M. I. Mitova, et al, JNP, 2008, 71, 824 O

OH

O N 6

N O

O

590 Streptophenazine E Type: Phenazine alkaloids. C22H24N2O5 Amorph. yellow solid, [α]D20 = −34° (c = 0.02, MeOH). Source: Marine-derived streptomycete Streptomyces sp. HB202. Pharm: Antibacterial (Bacillus subtilis, 62.5 μg/mL). Ref: M. I. Mitova, et al, JNP, 2008, 71, 824 O

OH

O N 6

N O

O

591 Streptophenazine H Type: Phenazine alkaloids. C24H28N2O6 Amorph. red solid, [α]D20 = −24° (c = 0.02, MeOH). Source: Marine-derived streptomycete Streptomyces sp. HB202. Pharm: Antibacterial (Bacillus subtilis, 15.6 μg/mL). Ref: M. I. Mitova, et al, JNP, 2008, 71, 824 O O N 6

N O

O

OH

OH 6'

218

7 Pyrimidines and Pyrazines

592 Bioxalomycin α1 Type: Naphthyridinomycins. C20H25N3O5 Powder. Source: Marine-derived streptomycetes Streptomyces viridostaticus ssp. littoralis LL-31F508. Pharm: Antimicrobial (poteny); antineoplastic (potent). Ref: V. S. Bernan, et al, J. Antibiot., 1994, 47, 1417│J. Zaccardi, et al, JOC, 1994, 59, 4045 OH

O H

H

O

H N H NH H

H

N

OH

H O

593 Bioxalomycin α2 Type: Naphthyridinomycins. C21H27N3O5 Powder, [α]D25 = +31° (MeOH). Source: Marine-derived streptomycetes Streptomyces viridostaticus ssp. littoralis LL-31F508. Pharm: Antimicrobial (poteny); antineoplastic (potent). Ref: V. S. Bernan, et al, J. Antibiot., 1994, 47, 1417│J. Zaccardi, et al, JOC, 1994, 59, 4045 OH

O H

H

O

H N H N H OH

H

N H O

594 Bioxalomycin β1 Type: Naphthyridinomycins. C20H23N3O5 Source: Marine-derived streptomycetes Streptomyces viridostaticus ssp. littoralis LL-31F508. Pharm: Antimicrobial (poteny); antineoplastic (potent). Ref: V. S. Bernan, et al, J. Antibiot., 1994, 47, 1417│J. Zaccardi, et al, JOC, 1994, 59, 4045 O

O H

H

O

H N H

NH H

O

H

N H O

7.2 Pyrazines

219

595 Bioxalomycin β2 Type: Naphthyridinomycins. C21H25N3O5 Source: Marine-derived streptomycetes Streptomyces viridostaticus ssp. littoralis LL-31F508. Pharm: Antimicrobial (poteny); antineoplastic (potent). Ref: V. S. Bernan, et al, J. Antibiot., 1994, 47, 1417│J. Zaccardi, et al, JOC, 1994, 59, 4045 O

O

H

H

O

H H

N N

O

H

H

N O

H

596 Cribrostatin 4 Renieramycin H Type: Saframycins. C30H30N2O10 Red prisms (MeOH), mp 190–192 °C (dec). Source: Sponges Cribrochalina sp. and Haliclona cribicutis (India waters). Pharm: Cytotoxic (BXPC3, GI50 = 5.6 μg/mL; SK-N-SH, GI50 = 3.6 μg/mL; OVCAR-3, GI50 = 2.2 μg/mL; SF295, GI50 > 10 μg/mL; SW1736, GI50 > 10 μg/mL; NCI-H460, GI50 > 10 μg/mL; KM20L2, GI50 > 10 μg/mL; FADU, GI50 = 0.26 μg/mL; DU145, GI50 > 10 μg/mL; P388, GI50 = 24.6 μg/mL); antibacterial (Neisseria gonorrheae ATCC 49226, MIC = 6.25–12.5 μg/disk; PRNG (clinical isolate), MIC = 1.56–3.12 μg/disk; Bacillus subtilis (Presque Isle 620), MIC = 12.5–25 μg/disk; Streptococcus pneumoniae (ATCC 6303), MIC = 6.25–12.5 μg/disk; PRSP (clinical isolate), MIC = 50–100 μg/disk). Ref: P. S. Pasameswaran, et al, Ind. J. Chem., Sect. B, 1998, 37, 1258│G. R. Pettit, et al, JNP, 2000, 63, 793│N. Saito, et al, Heterocycles, 2001, 55, 21 O HO O OH N O

N

O O

O

O

O

597 Ecteinascidin 583 Type: Saframycins. C29H35N3O9S Light yellow solid, [α]D22 = −47° (c = 0.14, CHCl3/MeOH 6:1). Source: Ascidian Ecteinascidia turbinata. Pharm: Cytotoxic (P388, IC50 = 10 ng/mL; A549, IC50 = 10 ng/mL; HT29, IC50 = 10 ng/mL; MEL28, IC50 = 5.0 ng/mL; CV-1,

220

7 Pyrimidines and Pyrazines

IC50 = 25 ng/mL); protein synthesis inhibitor (IC50 = 1.0 μg/mL); DNA synthesis inhibitor (IC50 = 1.0 μg/mL); RNA synthesis inhibitor (IC50 = 0.4 μg/mL); RNA polymerase inhibitor (IC50 = 0.5 μg/mL); antibacterial (Bacillus subtilis, MIC = 0.74 μg/disk). Ref: R. Sakai, et al, JACS, 1996, 118, 9017 O

O

HO

O

H

H NH

N

O OH O

H OH

S

O NH2

598 Ecteinascidin 594 Type: Saframycins. C30H32N2O10S Light yellow solid, [α]D22 = −58° (c = 1.1, CHCl3). Source: Ascidian Ecteinascidia turbinata (Caribbean Sea). Pharm: Cytotoxic (P388, IC50 = 10 ng/mL; A549, IC50 = 20 ng/mL; HT29, IC50 = 25 ng/mL; MEL28, IC50 = 25 ng/ mL; CV-1, IC50 = 25 ng/mL); protein synthesis inhibitor (IC50 = 0.8 μg/mL); DNA synthesis inhibitor (IC50 = 0.5 μg/mL); RNA synthesis inhibitor (IC50 = 0.5 μg/mL); RNA polymerase inhibitor (IC50 = 1.0 μg/mL); antibacterial (Bacillus subtilis, MIC = 0.37 μg/disk). Ref: R. Sakai, et al, JACS, 1996, 118, 9017 O

O

HO

O

H

H N

N

H

O O

S

O

OH

O O

599 Ecteinascidin 729 Type: Saframycins. C38H41N3O11S Source: Ascidian Ecteinascidia turbinata. Pharm: Cytotoxic (P388, IC50 = 0.2 ng/mL; A549, IC50 = 0.2 ng/mL; HT29, IC50 = 0.5 ng/mL; MEL28, IC50 = 5.0 ng/mL; CV-1, IC50 = 2.5 ng/mL); protein synthesis inhibitor (IC50 > 1 μg/mL); DNA synthesis inhibitor (IC50 = 0.2 μg/mL); RNA synthesis inhibitor (IC50 = 0.02 μg/mL); DNA polymerase inhibitor (IC50 = 1.5 μg/mL); RNA polymerase inhibitor (IC50 = 0.05 μg/mL); antibacterial (Bacillus subtilis, MIC = 0.08 μg/

7.2 Pyrazines

221

disk); immunoregulator; antineoplastic (P388, 12.5 μg/kg per day, T/C = 190% (1/6 survivors); B16, 12.5 μg/kg per day, T/C = 253%; Lewis lung carcinoma, 25 μg/kg per day, T/C = 0.00%; LX-1, 25 μg/kg per day, T/C = 0.00%; M5076, 12.5 μg/kg per day, T/C > 204% (5/10 survivors); MX-1, 37.5 μg/kg per day, T/C = 0.05%) (Sakai, 1992). Ref: A. E. Wright, et al, JOC, 1990, 55, 4508│K. L. Rinehart, et al, JOC, 1990, 55, 4512│Sakai, et al, Proc. Natl. Acad. Sci. U.S.A., 1992, 89, 11456│R. Sakai, et al, JACS, 1996, 118, 9017 O

O HO O

H S

O O

12 21

N

NH

OH

O

O O

NH

HO

600 Ecteinascidin 736 Type: Saframycins. C40H42N4O9S Fine needles (MeCN aq), mp 140–150 °C (dec), [α]D = −76° (c = 0.5, CHCl3). Source: Ascidian Ecteinascidia turbinata. Pharm: Cytotoxic (plate assay, L1210, 5.0 ng/mL, InRt = 90%). Ref: R. Sakai, et al, Proc. Natl. Acad. Sci. U.S.A., 1992, 89, 11456│R. Sakai, et al, JACS, 1996, 118, 9017 O

O O

HO H

H

12

N

N H

O O

S

OH

O O

H N HN

601 Ecteinascidin 743 Type: Saframycins. C39H43N3O11S Source: Ascidian Ecteinascidia turbinata. Pharm: Cytotoxic (P388, IC50 = 0.2 ng/mL; A549, IC50 = 0.2 ng/mL; HT29, IC50 = 0.5 ng/mL; MEL28, IC50 = 5.0 ng/mL; CV-1, IC50 = 1.0 ng/mL); protein synthesis inhibitor (IC50 > 1 μg/mL); antineoplastic (investigated for treatment of a variety of hmn tumours including soft tissue sarcomas, osteosarcoma, melanoma and breast cancer,

222

7 Pyrimidines and Pyrazines

mechanisms of action include inhibition of minor-groove-interacting transcription factors, in phase II clinical trials, 2003, granted orphan drug status by FDA (2004) for treatment of soft tissue sarcoma); DNA synthesis inhibitor (IC50 = 0.1 μg/mL); RNA synthesis inhibitor (IC50 = 0.03 μg/mL); DNA polymerase inhibitor (IC50 = 2 μg/ mL); RNA polymerase inhibitor (IC50 = 0.1 μg/mL); antibacterial (Bacillus subtilis, MIC = 0.02 μg/disk). Ref: A. E. Wright, et al, JOC, 1990, 55, 4508│K. L. Rinehart, et al, JOC, 1990, 55, 4512│R. Sakai, et al, JACS, 1996, 118, 9017│J. Jimeno, et al, Mar. Drugs, 2004, 2, 14 (rev) O

O

HO

O

S

12

N

N

21

O O

OH

O

O O

NH

HO

602 Ecteinascidin 745 Type: Saframycins. C39H43N3O10S Source: Ascidian Ecteinascidia turbinata. Pharm: Antineoplastic; immunoregulator. Ref: A. E. Wright, et al, JOC, 1990, 55, 4508│K. L. Rinehart, et al, JOC, 1990, 55, 4512│R. Sakai, et al, JACS, 1996, 118, 9017 O

O HO O H S N

12 21

N

O O

O

O O

NH

HO

603 Ecteinascidin 759B Type: Saframycins. C39H43N3O12S Source: Ascidian Ecteinascidia turbinata. Pharm: Antineoplastic. Ref: R. Sakai, et al, JACS, 1996, 118, 9017│R. S. Cvetkovic, et al, Drugs, 2002, 62, 1185

7.2 Pyrazines

223

O

O

HO

O

O S

12

N

N

21

O O

OH

O

O O

NH

HO

604 Ecteinascidin 770 Type: Saframycins. C40H42N4O10S Prisms (MeOH), mp 216–218 °C (dec), [α]D24 = −58.5° (c = 1, CHCl3). Source: Ascidians Ecteinascidia turbinata and Ecteinascidia thurstoni. Pharm: Cytotoxic (HCT116, IC50 = 1.2 nmol/L; QG56, IC50 = 3.9 nmol/L; NCI-H460, IC50 = 0.64 nmol/L; DLD-1, IC50 = 2.4 nmol/L); immunoregulator. Ref: K. Suwanborirux, et al, JNP, 2002, 65, 935; 2003, 66, 1441 O HO O

O

S

H 12

N

N

21

O O

CN O

O O

NH

HO

605 Jorumycin Type: Saframycins. C27H30N2O9 Unstable pale yellow powder, [α]D = −57° (c = 0.05, CHCl3). Source: Nudibranch Jorunna funebris from sponge Oceanapia sp. (Mandapam coast of India). Pharm: Cytotoxic (NIH3T3, 50 μg/mL, inhibitive rate = 100%; different tumor cell lines, IC50 = 125.5 μg/mL); antibacterial (inhibits growth of various grampositive bacteria at lower than 50 ng/mL). Ref: A. Fontana, et al, Tetrahedron, 2000, 56, 7305

224

7 Pyrimidines and Pyrazines

O O O

H

O

N N

O O

O

OH

606 Renieramycin A Type: Saframycins. C30H34N2O9 [α]D20 = −36.3° (c = 0.16, MeOH). Source: Sponge Reniera sp. Pharm: Antibacterial (Staphylococcus aureus and Bacillus subtilis). Ref: J. M. Frincke, et al, JACS, 1982, 104, 265│H. He, et al, JOC, 1989, 59, 5822│T. Fukuyama, et al, Tet. Lett., 1990, 31, 5989 O O 18

O

15

H 4

N

O O

O N

3 21

14

OH

O O

607 Renieramycin B Type: Saframycins. C32H38N2O9 [α]D20 = −32.2° (c = 0.15, MeOH). Source: Sponge Reniera sp. Pharm: Antibacterial. Ref: J. M. Frincke, et al, JACS, 1982, 104, 265│H. He, et al, JOC, 1989, 59, 5822│T. Fukuyama, et al, Tet. Lett., 1990, 31, 5989 O O O

H

O N

N

O O

O O

O

7.2 Pyrazines

225

608 Renieramycin C Type: Saframycins. C30H32N2O10 [α]D20 = −89.2° (c = 0.065, MeOH). Source: Sponge Reniera sp. Pharm: Antibacterial. Ref: J. M. Frincke, et al, JACS, 1982, 104, 265│H. He, et al, JOC, 1989, 59, 5822│T. Fukuyama, et al, Tet. Lett., 1990, 31, 5989 O O O

H

O N OH

N

O O

O

O

O

609 Renieramycin D Type: Saframycins. C32H36N2O10 [α]D20 = −100.7° (c = 0.092, MeOH). Source: Sponge Reniera sp. Pharm: Antibacterial. Ref: J. M. Frincke, et al, JACS, 1982, 104, 265│H. He, et al, JOC, 1989, 59, 5822│T. Fukuyama, et al, Tet. Lett., 1990, 31, 5989 O O O

H

O N O

N

O O

O

O

O

610 Renieramycin G Type: Saframycins. C30H32N2O9 Source: Sponge Xestospongia caycedoi (Fiji). Pharm: Cytotoxic (KB, MIC = 0.5 μg/mL; LoVo, MIC = 1.0 μg/mL). Ref: B. S. Davidson, Tet. Lett., 1992, 33, 3721

226

7 Pyrimidines and Pyrazines

O O O O N

O O

O

N

O

O

611 Renieramycin I Type: Saframycins. C31H32N2O10 Source: Sponge Haliclona cribricutis (India waters). Pharm: Antimicrobial. Ref: P. S. Parameswaran, et al, Ind. J. Chem., Sect. B, 1998, 37, 1258 O O 18

O

15

O 4

N

O O

N

3

22

O

21

14

O

O

O

612 Renieramycin M Type: Saframycins. C31H33N3O8 Dark yellow prisms (EtOAc), mp 194.5–197 °C, [α]D20 = −49.5° (c = 1, CHCl3). Source: Sponge Xestospongia sp. (pre-treated with KCN, maior metabolite, Thailand). Pharm: Cytotoxic (HCT116, IC50 = 7.9 nmol/L; QG56, IC50 = 19 nmol/L; NCI-H460, IC50 = 5.9 nmol/L; DLD-1, IC50 = 9.6 nmol/L). Ref: K. Suwanborirux, et al, JNP, 2003, 66, 1441; 2004, 67, 1023

7.2 Pyrazines

227

O O 18

O

O

4

N

3

N

O O

15

H 14

21

22

O

N

O

613 Renieramycin N Type: Saframycins. C31H35N3O9 Pale yellow prisms (EtOH), mp 162.5–164 °C, [α]D20 = −24.7° (c = 0.01, MeOH). Source: Sponge Xestospongia sp. (pre-treated with KCN, maior metabolite, Thailand). Pharm: Cytotoxic (HCT116, IC50 = 5.6 nmol/L; QG56, IC50 = 11 nmol/L; NCI-H460, IC50 = 6.7 nmol/L; DLD-1, IC50 = 5.7 nmol/L). Ref: K. Suwanborirux, et al, JNP, 2003, 66, 1441; 2004, 67, 1023 O HO O

H

OH N OH

N

O O

O

CN

O

614 Renieramycin O Type: Saframycins. C31H33N3O9 Pale yellow powder, [α]D20 = −134.4° (c = 0.7, CHCl3), oxidation product of Renieramycin N. Source: Sponge Xestospongia sp. (pre-treated with KCN, yield = 0.27%, Thailand). Pharm: Cytotoxic (HCT116, IC50 = 0.028 μmol/L; QG56, IC50 = 0.040 μmol/L). Ref: K. Suwanborirux, et al, JNP, 2003, 66, 1441; 2004, 67, 1023

228

7 Pyrimidines and Pyrazines

O O O

H

O N OH

N

O O

O

CN

O

615 Renieramycin Q Type: Saframycins. C31H33N3O9 Pale yellow solid, [α]D18 = −69.8° (c = 0.1, CHCl3). Source: Sponge Xestospongia sp. (pre-treated with KCN, yield = 0.11%, Thailand). Pharm: Cytotoxic (HCT116, IC50 = 0.059 μmol/L; QG56, IC50 = 0.071 μmol/L). Ref: K. Suwanborirux, et al, JNP, 2003, 66, 1441; 2004, 67, 1023 O HO O

H

OH N O

N

O O

O

CN

O

616 Renieramycin R Type: Saframycins. C32H35N3O9 Pale yellow solid, [α]D18 = −17.6° (c = 0.1, CHCl3). Source: Sponge Xestospongia sp. (pre-treated with KCN, yield = 0.62%, Thailand). Pharm: Cytotoxic (HCT116, IC50 = 0.023 μmol/L; QG56, IC50 = 0.029 μmol/L). Ref: K. Suwanborirux, et al, JNP, 2003, 66, 1441; 2004, 67, 1023

7.2 Pyrazines

229

O O O

H

O N O

N

O O

O

CN

O

617 Renieramycin S Type: Saframycins. C30H31N3O8 Pale yellow needles (EtOAc/petrol), mp 179–180 °C, [α]D20 = −38.8° (c = 0.1, CHCl3). Source: Sponge Xestospongia sp. (pre-treated with KCN, yield = 0.09%, Thailand). Pharm: Cytotoxic (HCT116, IC50 = 0.015 μmol/L; QG56, IC50 = 0.026 μmol/L). Ref: K. Suwanborirux, et al, JNP, 2003, 66, 1441; 2004, 67, 1023 O O O

H

O N

N

HO O

O

CN

O

618 Xestomycin Type: Saframycins. C27H30N2O9 Yellow powder, [α]D = −56° (MeOH). Source: Sponge Xestospongia sp. Pharm: Antibacterial. Ref: N. K. Gulavita, et al, CA, 1992, 117, 230454q

230

7 Pyrimidines and Pyrazines

O O 18

O

15

H

O

4

N

3 21

N

O O

14

OH

22

O O

619 Aniquinazoline D Type: Tryptoquivalines. C24H22N4O4 Yellowish solid, [α]D20 = −33° (c = 0.37, MeOH). Source: Mangrove-derived fungus Aspergillus nidulans MA-143 (endophytic) from mangrove Rhizophora stylosa (leaves, unspecified location, presumably China). Pharm: Toxic (brine shrimp, LD50 = 3.42 μmol/L, control Colchicines, LD50 = 88.4 mmol/L). Ref: C. -Y. An, et al, Mar. Drugs, 2013, 11, 2682

O

N N HO

O H N

N

O

620 Cladoquinazoline Type: Tryptoquivalines. C23H22N4O4 Source: Mangrove-derived fungus Cladosporium sp. PJX-41. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 100–150 μmol/L, weak). Ref: J. Peng, et al, JNP, 2013, 76, 1133

3R

N

NH

4

N

1 14R

O

16R

O O

HO NH

7.2 Pyrazines

231

621 epi-Cladoquinazoline Type: Tryptoquivalines. C23H22N4O4 Source: Mangrove-derived fungus Cladosporium sp. PJX-41. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 100–150 μmol/L, weak). Ref: J. Peng, et al, JNP, 2013, 76, 1133

3S

N

NH

4 1

N

14R

O

16R

O O

HO NH

622 Fumiquinazoline A Type: Tryptoquivalines. C24H23N5O4 Cryst. (CH2Cl2), mp 178–182 °C, [α]D33 = −214.5° (c = 0.47, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from fish Pseudolabrus japonicus. Pharm: Cytotoxic (P388, ED50 = 6.1 μg/mL) Ref: A. Numata, et al, Tet. Lett., 1992, 33, 1621│C. Takahashi, et al, JCS Perkin I, 1995, 2345│B. B. Snider, et al, Org. Lett., 2000, 2, 4103

HN

N 4

N

O

H

HO

O

H N

NH

O

623 Fumiquinazoline B Type: Tryptoquivalines. C24H23N5O4 Cryst. (Me2CO), mp 174–176 °C, [α]D21 = −196.7° (c = 0.38, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from fish Pseudolabrus japonicus. Pharm: Cytotoxic (P388, ED50 = 16.0 μg/mL) Ref: A. Numata, et al, Tet. Lett., 1992, 33, 1621│C. Takahashi, et al, JCS Perkin I, 1995, 2345│B. B. Snider, et al, Org. Lett., 2000, 2, 4103

232

7 Pyrimidines and Pyrazines

4

HN

H

N N

O HO

O H NH

N O

624 Fumiquinazoline C Type: Tryptoquivalines. C24H21N5O4 Cryst. +1Me2CO (Me2CO), mp 244–246 °C, [α]D21 = −193.7° (c = 0.31, CHCl3); mp 239-243 °C (ethylacetate), [α]D22 = −160.4° (c = 0.027, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from fish Pseudolabrus japonicus (gastrointestinal tract), marine-derived fungus Aspergillus fumigatus KMM 4631. Pharm: Cytotoxic (P388, ED50 = 52.0 μg/mL). Ref: A. Numata, et al, Tet. Lett., 1992, 33, 1621│C. Takahashi, et al, JCS Perkin I, 1995, 2345│S. S. Afiyatullov, et al, Chem. Nat. Compd. (Engl. Transl.), 2005, 41, 236 O N

HN H O N

NH N H

O

O

625 Fumiquinazoline D Type: Tryptoquivalines. C24H21N5O4 Prisms (Me2CO), mp 214–216 °C, [α]D22 = +86.2° (c = 0.15, CHCl3); mp 210-214 °C (ethylacetate), mp 212–215 °C (ethylacetate), [α]D22 = +86.2° (c = 0.15, CHCl3). Source: Marine-derived fungi Aspergillus fumigatus from fish Pseudolabrus japonicus (gastrointestinal tract), and Aspergillus fumigatus KMM 4631. Pharm: Cytotoxic (P388, ED50 = 13.5 μg/mL) Ref: A. Numata, et al, Tet. Lett., 1992, 33, 1621│C. Takahashi, et al, JCS Perkin I, 1995, 2345│S. S. Afiyatullov, et al, Chem. Nat. Compd. (Engl. Transl.), 2005, 41, 236

7.2 Pyrazines

233

N NH N O O

OH

H N N O

626 Fumiquinazoline E Type: Tryptoquivalines. C25H25N5O5 Pale yellow powder, mp 168–172 °C, [α]D = −143.3° (c = 0.2, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from fish Pseudolabrus japonicus (gastrointestinal tract). Pharm: Cytotoxic (P388, ED50 = 13.8 μg/mL) Ref: A. Numata, et al, Tet. Lett., 1992, 33, 1621│C. Takahashi, et al, JCS Perkin I, 1995, 2345 O N

HN

4

N

O

H

HO

H

O H N

N O

627 Fumiquinazoline F Type: Tryptoquivalines. C21H18N4O2 Pale yellow powder, mp 88–90 °C, [α]D = −411.2° (c = 1.4, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from fish Pseudolabrus japonicus (gastrointestinal tract). Pharm: Cytotoxic (P388, ED50 = 14.6 μg/mL). Ref: A. Numata, et al, Tet. Lett., 1992, 33, 1621│C. Takahashi, et al, JCS Perkin I, 1995, 2345│B. B. Snider, et al, Org. Lett., 2000, 2, 4103│H. Wang, et al, JOC, 2000, 65, 1022

N 4

NH

N

O

O

N

234

7 Pyrimidines and Pyrazines

628 Fumiquinazoline G Type: Tryptoquivalines. C21H18N4O2 Pale yellow powder, mp 119–121 °C, [α]D = −462.8° (c = 0.6, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from fish Pseudolabrus japonicus (gastrointestinal tract). Pharm: Cytotoxic (P388, ED50 = 17.7 μg/ mL). Ref: A. Numata, et al, Tet. Lett., 1992, 33, 1621│C. Takahashi, et al, JCS Perkin I, 1995, 2345│B. B. Snider, et al, Org. Lett., 2000, 2, 4103│H. Wang, et al, JOC, 2000, 65, 1022

N 4

NH

N

O

O

N

629 Fumiquinazoline H Type: Tryptoquivalines. C27H27N5O4 Pale yellow solid, mp 144–147 °C, [α]D = −59° (c = 0.001, CHCl3). Source: Marine-derived fungus Acremonium sp. from ascidian Ecteinascidia turbinata (Bahamas). Pharm: Antifungal (broth microdilution assay, Candida albicans, 0.5 mg/mL (1 mmol/L). weak). Ref: G. N. Belofsky, et al, Chem. Eur. J., 2000, 6, 1355 O N N H

H

O

N NH N H O

O

630 Fumiquinazoline I Type: Tryptoquivalines. C27H29N5O4 Solid, mp 116–120 °C, [α]D = −138° (c = 0.001, CHCl3). Source: Marine-derived fungus Acremonium sp. from ascidian Ecteinascidia turbinata (Bahamas). Pharm: Antifungal (broth microdilution assay, Candida albicans, 0.5 mg/mL (1 mmol/L). weak). Ref: G. N. Belofsky, et al, Chem. Eur. J., 2000, 6, 1355

7.2 Pyrazines

235

N NH N

O

O HO

H H N N O

631 Fumiquinazoline J Type: Tryptoquivalines. C20H19N3O4 Source: Marine-derived fungus Aspergillus fumigatus H1-04. Pharm: Cytotoxic (tsFT210, P388, HL60, A549 and Bel7402). Ref: X. -X. Han, et al, Chin. J. Med. Chem., 2007, 17, 232 O

N

O H H N

O

N O

632 Fumiquinazoline L (Zhou, 2013) Type: Tryptoquivalines. C25H23N5O5 Source: Marine-derived fungus Aspergillus sp. from sponge Tethya aurantium (Limski canal, N. Adriatic Sea, Croatia). Pharm: Na/ K-ATPase inhibitor (IC50 = 20 μmol/L, weak). Ref: Y. Zhou, et al, EurJOC, 2013, 5, 894│L. Liao, et al, .JNP, 2015, 78, 349 HO N

NH N

O

O

OH

N

NH

O

633 Fumiquinazoline S Type: Tryptoquivalines. C29H31N5O5 Pale yellow amorphous solid, [α]D25 = −105 ° (c = 0.5, MeOH), [α]D25 = −151° (c = 0.25, CHCl3). Source: Marine-derived fungus

236

7 Pyrimidines and Pyrazines

Aspergillus sp. Pharm: Na/K-ATPase inhibitor (IC50 = 34 μmol/L, weak). Ref: L. Liao, et al, .JNP, 2015, 78, 349

N S

N

N

O

R

O

HO

O

H N

R

N

R

O

634 Fumitremorgin C Type: Tryptoquivalines. C22H25N3O3 Cryst. (EtOAc), [α]D28 = −13° (c = 0.53, MeOH). Source: Marine-derived fungus Aspergillus sydowi PFW1-13 (from driftwood sample, China). Pharm: Tremorgenic; mycotoxin; reverses of multidrug resistance in cells transfected (breast cancer resistance protein). Ref: M. Zhang, et al, JNP, 2008, 71, 985 O H N N O

N H H

H O

635 3-Hydroxyglyantrypine Type: Tryptoquivalines. C20H16N4O3 Source: Mangrove-derived fungus Cladosporium sp. PJX-41. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 100–150 μmol/L, weak). Ref: J. Peng, et al, JNP, 2013, 76, 1133 OH N NH

4 3

N

1 14R

O

O

16

NH

7.2 Pyrazines

237

636 Isochaetominine A Type: Tryptoquivalines. C22H18N4O4 Pale yellow amorphous solid, [α]D25 = −63° (c = 0.5, MeOH). Source: Marine-derived fungus Aspergillus sp. Pharm: Na/KATPase inhibitor (IC50 = 78 μmol/L, weak). Ref: L. Liao, et al, .JNP, 2015, 78, 349

O N

N

HO

14R

H N

O

N

O

637 Isochaetominine B Type: Tryptoquivalines. C23H20N4O4 Pale yellow amorphous solid, [α]D25 = −73° (c = 0.6, MeOH). Source: Marine-derived fungus Aspergillus sp. Pharm: Na/KATPase inhibitor (IC50 = 20 μmol/L, weak). Ref: L. Liao, et al, .JNP, 2015, 78, 349

O N

N

HO

14R

H N

O

N

O

638 Isochaetominine C Type: Tryptoquivalines. C24H22N4O4 Pale yellow amorphous solid, [α]D25 = −90° (c = 0.6, MeOH). Source: Marine-derived fungus Aspergillus sp. Pharm: Na/KATPase inhibitor (IC50 = 38 μmol/L, weak). Ref: L. Liao, et al, .JNP, 2015, 78, 349

O N

N

HO

14R

H N O

N

O

238

7 Pyrimidines and Pyrazines

639 14-epi-Isochaetominine C Type: Tryptoquivalines. C24H22N4O4 Pale yellow amorphous solid, [α]D25 = +33° (c = 0.7, MeOH). Source: Marine-derived fungus Aspergillus sp. Pharm: Na/KATPase inhibitor (IC50 = 57 μmol/L, weak). Ref: L. Liao, et al, .JNP, 2015, 78, 349

O N

N

HO

14S

H

O

N

N O

640 Norquinadoline A Type: Tryptoquivalines. C26H25N5O4 White solid, [α]D25 = −2.7° (c = 0.1, MeOH). Source: Mangrove-derived fungus Cladosporium sp. PJX-41. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 82 μmol/L, control Ribavirin, IC50 = 87 μmol/L). Ref: J. Peng, et al, JNP, 2013, 76, 1133 16

N

8

NH

4 3 1

N O

15

30

19

27

O

14

HO

N

21

NH H

O

641 (14R)-Oxoglyantrypine Type: Tryptoquivalines. C20H14N4O3 Yellow powder, [α]D25 = +230° (c = 0.1, CHCl3). Source: Mangrove-derived fungus Cladosporium sp. PJX-41. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 100–150 μmol/L, weak). Ref: J. Peng, et al, JNP, 2013, 76, 1133

7.2 Pyrazines

239

O N

NH

4 3 1

N

14R

O

O

16

NH

642 (14S)-Oxoglyantrypine Type: Tryptoquivalines. C20H14N4O3 Yellow powder, [α]D25 = −230° (c = 0.1, CHCl3). Source: Mangrove-derived fungus Cladosporium sp. PJX-41. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 85 μmol/L, control Ribavirin, IC50 = 87 μmol/L). Ref: J. Peng, et al, JNP, 2013, 76, 1133 O N

NH

4 3 1

N

14S

O

O

16

NH

643 Quinadoline B Type: Tryptoquivalines. C25H21N5O3 Source: Mangrove-derived fungus Cladosporium sp. PJX-41. Pharm: Antiviral (influenza A H1N1 virus, IC50 = 82 μmol/L, control Ribavirin, IC50 = 87 μmol/L). Ref: N. Koyama, et al, Org. Lett., 2008, 10, 5273│J. Peng, et al, JNP, 2013, 76, 1133 H

O N

N H

HN

N N O

O

8 Purines and Pteridines 8.1 Purines and Analogues 644 Adenine Vitamin B4 Type: Purines and analogues. C5H5N5 Needles +3H2O (H2O), mp 360–365 °C (anhydrous) dec. Source: Marine-derived streptomycete Streptomyces sp. Act8015, animals and plants tissues, in DNA and RNA. Pharm: Antiviral; vitamin. Ref: K. A. Shaaban, et al, J. Antibiot., 2008, 61, 736 NH2 N

N

N H

N

9

9H form

645 (–)-Ageloxime D Type: Purines and analogues. C26H40N5O1+ Source: Sponge Agelas nakamurai (Menjangan I., Bali, Indonesia). Pharm: Cytotoxic (L5178Y, IC50 = 12.5 μmol/L); antibacterial (Staphylococcus epidermidis, MIC > 45 μmol/L). Ref: T. Hertiani, et al, BoMC, 2010, 18, 1297

N N

+

N

N N H

OH

H

646 Aphrocallistin Type: Purines and analogues. C20H24Br2N6O2 Light brown oil. Source: Hexactinellid Sponge Aphrocallistes beatrix (unique marine natural product isolated from hexactinellid sponges (Hexactinellida) up to now, Fort Pierce, Florida). Pharm: Cytotoxic (causes G1 arrest in cells). Ref: A. E. Wright, et al, JNP, 2009, 72, 1178

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8 Purines and Pteridines

Br N

N N H

O

O

Br

N N N

647 Caissarone Type: Purines and analogues. C8H11N5O HCl: Needels (MeOH aq), mp 285–290 °C; Picrate: Crystal (EtOH), mp 245–250 °C. Source: Sea anemone Bunodosoma caissarum. Pharm: Toxic (teratogen). Ref: R. Zelnik, et al, JCS Perkin I, 1986, 2051│T. Saito, et al, CPB, 1993, 41, 1746 N H N

N

O N

N

648 Desmethylphidolopin Type: Purines and analogues. C13H11N5O5 Yellow amorph. powder. Source: Bryozoans Phidolopora pacifica and Diaperoecia californica. Pharm: Antifungal. Ref: M. Tischler, et al, Comp. Biochem. Physiol., B: Comp. Biochem., 1986, 84, 43 OH O H

N

N N

O

N

O

O

N

649 3,7-Dimethylisoguanine Type: Purines and analogues. C7H9N5O Source: Sponges Agelas longissima (Caribbean Sea) and Zyzzya fuliginosa. Pharm: Antiserotonin; actomyosin ATPase activator; immunostimulant; antimicrobial. Ref: F. Cafieri, et al, Tet. Lett., 1995, 36, 7893 NH2 N

N 7

1 3

O

N

N

8.1 Purines and Analogues

243

650 1,3-Dimethylisoguanine (1997) Type: Purines and analogues. C7H9N5O Powder; cryst. (salt). Source: Sponge Amphimedon viridis (Bermuda, Brazil). Pharm: Cytotoxic (26 hmn cancer cell lines assay, the highest cytotoxicity to ovarian cancer cell line, IC50 = 2.1 μg/mL). Ref: S. S. Mitchell, et al, JNP, 1997, 60, 727│C. C. Chehade, et al, JNP, 1997, 60, 729 NH N

N 1 3

O

N

N H

651 2-Hydroxy-1’-methylzeatin Type: Purines and analogues. C11H15N5O2 mp 300 °C, [α]D19 = +41.6° (c = 0.288, MeOH). Source: An unidentified green alga NIO-143, fungus Alternaria brassicae. Pharm: Cytokinin; stimulator of plant growth. Ref: A. H. A. Farooqi, et al, Phytochemistry, 1990, 29, 2061│J. S. Dahiya, et al, Phytochemistry, 1991, 30, 2825│T. Fujii, et al, Heterocycles, 1992, 34, 21

OH HN N

N HO

N

N H

652 Malonganenone A Type: Purines and analogues. C26H38N4O2 Colorless glass. Source: Gorgonians Leptogorgia gilchristi (near Ponto Malongane, Mozambique), Euplexaura robusta (Weizhou I., Guangxi, China) and Euplexaura nuttingi (Pemba I., Tanzania). Pharm: Cytotoxic (oesophageal cancers: WHCO1, IC50 = 17.0 μmol/L, WHCO5, IC50 = 31.6 μmol/L, WHCO6, IC50 = 29.1 μmol/L, KYSE70, IC50 = 35.9 μmol/L, KYSE180, IC50 = 21.7 μmol/L, KYSE520, IC50 = 17.8 μmol/L, MCF12, IC50 = 20.7 μmol/L; HeLa, IC50 = 1.56 μmol/L, control ADM, IC50 = 0.38 μmol/L, K562, IC50 = 0.35 μmol/L, ADM, IC50 = 0.23 μmol/L). 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

244

8 Purines and Pteridines

O 11'

O N

N N

N

653 Malonganenone D Type: Purines and analogues. C26H38N4O2 Oil. Source: Gorgonians Euplexaura nuttingi (Pemba I., Tanzania) and Euplexaura robusta (Weizhou I., Guangxi, China). Pharm: Cytotoxic (inhibits growth of K562 and UT7 cells); induces apoptosis (transformed mammalian cells, 1.25 μg/mL); cytotoxic (HeLa, IC50 = (7.62 ± 0.38)μmol/L, control ADM, IC50 = (0.38 ± 0.05)μmol/L; K562, IC50 = (4.54 ± 0.21)μmol/L, ADM, IC50 = (0.23 ± 0.02)μmol/L); kinase inhibitor (c-Met kinase, 10 μmol/L) (J. -R. Zhang, 2012). Ref: H. Sorek, et al, JNP, 2007, 70, 1104│J. -R. Zhang, et al, Chem. Biodiversity, 2012, 9, 2218 O N

N N

O

N

654 Malonganenone E Type: Purines and analogues. C26H38N4O2 Oil. Source: Gorgonians Euplexaura nuttingi (Pemba I., Tanzania) and Euplexaura robusta (Weizhou I., Guangxi, China). Pharm: Cytotoxic (inhibits growth of K562 and UT7 cells); induces apoptosis (transformed mammalian cells, 1.25 μg/mL); cytotoxic (HeLa, IC50 = (5.65 ± 0.35)μmol/L, control ADM, IC50 = (0.38 ± 0.05)μmol/L; K562, IC50 = (2.70 ± 0.28)μmol/L, ADM, IC50 = (0.23 ± 0.02)μmol/L) (J. -R. Zhang, 2012). Ref: H. Sorek, et al, JNP, 2007, 70, 1104│J. -R. Zhang, et al, Chem. Biodiversity, 2012, 9, 2218 O N

N N

O

N

655 Malonganenone I Type: Purines and analogues. C26H38N4O2 Colorless oil. Source: Gorgonian Euplexaura robusta (Weizhou I., Guangxi, China). Pharm: Cytotoxic (HeLa, IC50 = (10.82 ± 0.45)

8.1 Purines and Analogues

245

μmol/L, control ADM, IC50 = (0.38 ± 0.05)μmol/L; K562, IC50 = (8.69 ± 0.45)μmol/L, ADM, IC50 = (0.23 ± 0.02)μmol/L). Ref: J. -R. Zhang, et al, Chem. Biodiversity, 2012, 9, 2218 O O N

N

2

N

N

656 Malonganenone J Type: Purines and analogues. C26H38N4O Colorless oil. Source: Gorgonian Euplexaura robusta (Weizhou I., Guangxi, China). Pharm: Cytotoxic (HeLa, IC50 = (53.23 ± 2.24) μmol/L, control ADM, IC50 = (0.38 ± 0.05)μmol/L; K562, IC50 = (58.01 ± 2.38)μmol/L, ADM, IC50 = (0.23 ± 0.02)μmol/L). Ref: J. -R. Zhang, et al, Chem. Biodiversity, 2012, 9, 2218 O N

N

3

N

N

657 1-Methylherbipoline Type: Purines and analogues. C8H12N5O Source: Sponge Jaspis sp. ( Japan). Pharm: Collagenase inhibitor (Clostridium histolyticum collagenase, 1.25 mg/mL). Ref: H. Yagi, et al, JNP, 1994, 57, 837 O N

N H 2N

N

+

N

658 1-Methyl-6-iminopurine Type: Purines and analogues. C6H7N5 Cryst. (H2O), mp 296–299 °C (dec). Source: Sponges Geodia gigas and Hymeniacidon sanguinea, starfishes Asterias amurensis, Asterias rubens and Marthasterias glacialis. Pharm: Spawning-inducing factor in Asterias. Ref: G. Cimino, et al, JNP, 1985, 48, 523│CRC press, DNP on DVD, 2012, version 20.2

246

8 Purines and Pteridines

NH N

N

N H

N

659 Microxine Type: Purines and analogues. C8H11N5O4S Amorph. solid. Source: Sponge Microxina sp. (Australia). Pharm: cdc2 Kinase inhibitor (weak). Ref: K. B. Killday, et al, JNP, 2001, 64, 525│D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) O S

HN

OH O

N

N

O N

N

H

660 Mucronatine Type: Purines and analogues. C7H9N5O Solid, mp 200–202 °C. Source: Sponge Stryphnus mucronatus (Mediterranean Sea, France). Pharm: Toxic (brine shrimp, 2.8 mmol/L, InRt = 50%); antifoulant (phenoloxydase inhibitor, InRt = 37%). Ref: M. Bourguet-Kondracki, et al, Tet. Lett., 2001, 42, 7257 NH2 N

N

N

N

O

661 Nuttingine A Type: Purines and analogues. C27H40N4O3 Colorless oil. Source: Gorgonian Euplexaura nuttingi (Pemba I., Tanzania). Pharm: Cytotoxic (inhibits growth of K562 and UT7); induces apoptosis (transformed mammalian cells, 1.25 μg/mL). Ref: H. Sorek, et al, JNP, 2007, 70, 1104 O

O N

N 1 4

O

N

N 9

1'

3'

7'

11'

13'

8.1 Purines and Analogues

247

662 Nuttingine B Type: Purines and analogues. C27H40N4O3 Colorless oil. Source: Gorgonian Euplexaura nuttingi (Pemba I., Tanzania). Pharm: Cytotoxic (inhibits growth of K562 and UT7); induces apoptosis (transformed mammalian cells, 1.25 μg/mL). Ref: H. Sorek, et al, JNP, 2007, 70, 1104 O N

N 1

1'

3'

11'

7'

13'

4

O

O

N

N

9

663 Nuttingine C Type: Purines and analogues. C27H42N4O2 Colorless oil. Source: Gorgonian Euplexaura nuttingi (Pemba I., Tanzania). Pharm: Cytotoxic (inhibits growth of K562 (at 0.4 μg/mL, induced 30% inhibition of cell growth) and UT7 cells (0.4 μg/mL, induced 50% inhibition of cell growth) in dose- and time-dependent manner); induces apoptosis (transformed mammalian cells, 1.25 μg/mL). Ref: H. Sorek, et al, JNP, 2007, 70, 1104 O

O N

N

1'

3'

7'

11'

13'

1 4

N

N

9

664 Nuttingine D Type: Purines and analogues. C27H42N4O2 Colorless oil. Source: Gorgonian Euplexaura nuttingi (Pemba I., Tanzania). Pharm: Cytotoxic (inhibits growth of K562 (at 0.4 μg/mL, induced 30% inhibition of cell growth) and UT7 cells (0.4 μg/mL, induced 50% inhibition of cell growth) in dose- and time-dependent manner); induces apoptosis (transformed mammalian cells, 1.25 μg/mL). Ref: H. Sorek, et al, JNP, 2007, 70, 1104 O

O N

N 1

1'

3'

7'

11'

13'

4

N

N 9

665 Nuttingine E Type: Purines and analogues. C27H42N4O2 Colorless oil. Source: Gorgonian Euplexaura nuttingi (Pemba I., Tanzania). Pharm: Cytotoxic (inhibits growth of K562 (at 0.4 μg/mL,

248

8 Purines and Pteridines

induced 30% inhibition of cell growth) and UT7 cells (0.4 μg/mL, induced 50% inhibition of cell growth) in dose- and time-dependent manner); induces apoptosis (transformed mammalian cells, 1.25 μg/mL). Ref: H. Sorek, et al, JNP, 2007, 70, 1104 O N

N

3'

1'

7'

1

N

11' 13'

4

O

N 9

666 Phidolopin Type: Purines and analogues. C14H13N5O5 Cryst. (MeOH), mp 226–227 °C. Source: Bryozoan Phidolopora pacifica. Pharm: Antifungal; algicide. Ref: S. W. Ayer, et al, JOC, 1984, 49, 3869│K. Hirota, et al, Tet. Lett., 1985, 26, 2355 OH O N O

NO2 N

N

N

8.2 Pteridines and Analogues 667 Lumichrome Type: Pteridines and analogues. C12H10N4O2 Pale yellow cryst. (CHCl3 or AcOH aq), mp 300 °C (dec). Source: Ascidian Halocynthia roretzi. Pharm: Natural metamorphosis inducer (larvae of Halocynthia roretzi). Ref: S. Tsnkamoto, et al, Eur J. Biochem., 1999, 264, 785

N

H N

O NH

N O

668 Urochordamine A Type: Pteridines and analogues. C22H26BrN7O [α]D = +11.7° (c = 0.263, CHCl3). Source: Ascidians Ciona savignyi and Botrylloides sp. Pharm: Promotes larvae settlement and metamorphosis in ascidian Ciona savignyi; antibacterial. Ref: S. Tsukamoto, et al, Tet. Lett., 1993, 34, 4819

8.2 Pteridines and Analogues

N

HN

249

N H

N N O N N H

Br

H

669 Urochordamine B Type: Pteridines and analogues. C22H26BrN7O [α]D = −36.6° (c = 0.174, CHCl3). Source: Ascidians Ciona savignyi and Botrylloides sp. Pharm: Promotes larvae settlement and metamorphosis in ascidian Ciona savignyi; antibacterial. Ref: S. Tsukamoto, et al, Tet. Lett., 1993, 34, 4819

N

HN

N H

N

N

9

O Br

N N H

H

9 Sesquiterpene and Sesterterpene Alkaloids 9.1 Sesquiterpene Alkaloids 670 (‒)-Cavernothiocyanate Ax10 Type: Axane sesquiterpene slkaloids. C16H25NS [α]D = −37.8° (c = 0.037, CHCl3). Source: Sponges Acanthella cavernosa and Acanthella cf. cavernosa, nudibranch Phyllidia ocellata. Pharm: Larval metamorphosis inhibitor. Ref: N. Fusetani, et al, Tet. Lett., 1992, 33, 6823│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16

N

H S

671 7-Isothiocyanato-11-oppositene Ax9 Type: Axane sesquiterpene slkaloids. C16H25NS [α]D = −52.0° (c = 0.1, CHCl3). Source: Sponges Acanthella cavernosa (Japan waters) and Acanthella cf. cavernosa. Pharm: Antifoulant (inhibits settlement and metamorphosis of barnacle larvae). Ref: H. Hirota, et al, Tetrahedron, 1996, 52, 2359│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review)

H SCN

672 4-Formamidoeudesm-7-ene Eu27 Type: Eudesmane sesquiterpene alkaloids. C16H27NO Source: Sponge Axinyssa sp. (South China Sea). Pharm: Cytotoxic (hmn cancer cell lines CNE2, IC50 = 13.8 μg/ mL, HeLa, IC50 = 7.5 μg/mL, LO2, IC50 = 38.0 μg/mL). Ref: W. -J. Lan, et al, Helv. Chim. Acta, 2008, 91, 426│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review)

O H

H NH

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252

9 Sesquiterpene and Sesterterpene Alkaloids

673 Halichonadin C Eu11 Type: Eudesmane sesquiterpene alkaloids. C16H25N Amorph. solid, [α]D19 = −130° (c = 1, CHCl3). Source: Sponge Halichondria sp. Pharm: Antibacterial (Micrococcus luteus, MIC = 0.52 μg/mL). Ref: H. Ishiyama, et al, Tetrahedron, 2005, 61, 1101│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review)

10 7

5

H

6

NC

674 4-Isothiocyanato-7α-eudesm-11-ene Eu20 Type: Eudesmane sesquiterpene alkaloids. C16H25NS Cryst. (Et2O), mp 62.3 °C, [α]D25 = +142.9° (c = 0.035, CHCl3). Source: Sponges Acanthella klethra (Pelorus Is., Queensland, Australia; Great Barrier Reef), Acanthella cavernosa (Heron I., Great Barrier Reef, Australia), Acanthella cavernosa (Mudjimba I., Mooloolaba, Australia) and Axinyssa isabela (Isabel I., Nayarit, Mexico). Pharm: Antiplasmodial (Plasmodium falciparum, chloroquine-sensitive strain D6, IC50 = 4000 ng/mL, chloroquine-resistant strain W2, IC50 = 550 ng/mL). Ref: G. M. König, et al, JNP, 1992, 55, 633│R. J. Clark, et al, Tetrahedron, 2000, 56, 3071│P. Jumaryatno, et al, JNP, 2007, 70, 1725│E. Zubía, et al, JNP, 2008, 71, 2004│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review)

H

SCN

675 4-Isothiocyanato-7β-eudesm-11-ene Eu24 Type: Eudesmane sesquiterpene alkaloids. C16H25NS Oil, [α]D25 = +180° (c = 0.025, CHCl3). Source: Sponges Acanthella klethra (Pelorus Is., Queensland, Australia; Great Barrier Reef) and Acanthella sp., dorid nudibranch Cadlina luteomarginata (Conehead Point, Rennell Sound, Graham I., British Columbia). Pharm: Antiplasmodial (Plasmodium falciparum, chloroquine-sensitive strain D6, IC50 > 10 μg/ mL, chloroquine-resistant strain W2, IC50 > 10 μg/mL, inversion of configuration at C-7 leads to a drastic activity reduction). Ref: G. M. König, et al. JNP, 1992, 55, 633│D. L. Burgoyne, et al, Tetrahedron, 1993, 49, 4503│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review)

9.1 Sesquiterpene Alkaloids

253

H SCN

676 11-Isothiocyano-7βH-eudesm-5-ene Eu17 Type: Eudesmane sesquiterpene alkaloids. C16H25NS Oil, [α]D = −89.7° (c = 0.8, CHCl3). Source: Sponges Axinella cannabina (Taranto, near Porto Cesareo, Italy), Acanthella pulcherrima (Weed Reef, Darwin, Australia), Phyllidia pustulosa (Negros I., Cebu I., San Sebastian, Cebu, Philippines) and Acanthella klethra (Pelorus Is., Queensland, Australia), sponge Acanthella sp. and dorid nudibranch Cadlina luteomarginata (Conehead Point, Rennell Sound, Graham I., British Columbia), sponges Axinyssa ambrosia (Santa Marta Bay, Caribbean Sea, Colombia) and Acanthella cavernosa (Coral Gardens, Gneerings Reef, Mooloolaba, Australia). Pharm: Cytotoxic (cultured KB-3 cells, IC50 > 20 μg/mL); antiplasmodial (Plasmodium falciparum, chloroquine-sensitive strain D6, IC50 = 2240 ng/mL, chloroquine-resistant strain W2, IC50 = 610 ng/mL). Ref: P. Ciminiello, et al, Can. J. Chem., 1987, 65, 518│R. Capon, et al, Aust. J. Chem., 1988, 41, 979│K. E. Kassuhlke, et al, JOC, 1991, 56, 3747│G. M. König, et al, JNP, 1992, 55, 633│C. K. Angerhofer, et al, JNP, 1992, 55, 1787│D. L. Burgoyne, et al, Tetrahedron, 1993, 49, 4503│N. V. Petrichtcheva, et al, JNP, 2002, 65, 851│P. Jumaryatno, et al, JNP, 2007, 70, 1725│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review)

NCS

677 Axiplyn C Ca34 Type: Cadinane sesquiterpene alkaloids. C16H25NOS Source: Sponge Axinyssa sp. (Gulf of California). Pharm: Antifoulant (larvae of the acorn barnacle Balanus Amphitrite, ID50 = 1.8 μg/mL). Ref: E. Zubía, et al, JNP, 2008, 71, 608 NCS

H HO

4

1

10 7

678 Axiplyn D Fu16 Type: Cadinane sesquiterpene alkaloids. C16H25NO3S Source: Sponge Axinyssa aplysinoides (Misali I., Tanzania). Pharm: Antifoulant (larvae of the acorn barnacle

254

9 Sesquiterpene and Sesterterpene Alkaloids

Balanus Amphitrite, IC50 = 1.6 μg/mL). Ref: H. Sorek, et al, Tet. Lett., 2008, 49, 2200│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review) NCS O H OH

HO

679 Axiplyn E Fu17 Type: Cadinane sesquiterpene alkaloids. C16H25NO3S Source: Sponge Axinyssa aplysinoides (Misali I., Tanzania). Pharm: Antifoulant (larvae of the acorn barnacle Balanus Amphitrite, IC50 = 1.5 μg/mL). Ref: H. Sorek, et al, Tet. Lett., 2008, 49, 2200│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review) NCS

HO HO

H O

680 (–)-10-Isocyano-4-amorphene Ca2 Type: Cadinane sesquiterpene alkaloids. C16H25N Source: Sponges Halichondria sp. (North coast of O’ahu, Hawaii), Axinyssa sp. (Gun Beach, Guam) and Acanthella acuta, dorid nudibranch Phyllidia ocellata (Kamikoshiki-jima I., Japan). Pharm: Antifoulant (larvae of acorn barnacle Balanus Amphitrite, IC50 = 7.2 μg/mL). Ref: B. J. Burreson, et al, J. Chem. Soc., Chem. Commun. 1974, 1035│B. J. Burreson, et al, JACS, 1975, 97, 201│B. J. Burreson, et al, Tetrahedron, 1975, 31, 2015│A. H. Marcus, et al, JOC, 1989, 54, 5184│T. Okino, et al, Tetrahedron, 1996, 52, 9447 NC

H 10 4

1 7

H

681 10-Isocyano-4-cadinene Ca13 Type: Cadinane sesquiterpene alkaloids. C16H25N Source: Dorid nudibranches Phyllidia pustulosa and Phyllidia varicosa (Kamikoshiki-jima/Shimokoshiki I., Japan). Pharm: Antifoulant (larvae of acorn barnacle Balanus Amphitrite, IC50 = 0.14 μg/mL). Ref: T. Okino, et al, Tetrahedron, 1996, 52, 9447

9.1 Sesquiterpene Alkaloids

NC

H 10

1

4

255

7

H

682 (1S*,4S*,7R*,10S*)-10-Isocyano-5-cadinen-4-ol Ca21 Type: Cadinane sesquiterpene alkaloids. C16H25NO [α]D = +88.8° (c = 0.025, CHCl3). Source: Dorid nudibranch Phyllidia pustulosa (Katsuura, Kii Penisula, Japan). Pharm: Antifoulant (larvae of acorn barnacle Balanus Amphitrite, IC50 = 0.17 μg/mL). Ref: H. Hirota, et al, Tetrahedron, 1998, 54, 13971 NC

H HO

4

10

1

7

683 10-Isocyano-5-cadinen-4-ol Type: Cadinane sesquiterpene alkaloids. C16H25NO Source: Dorid nudibranch Phyllidia pustulosa (Japan waters). Pharm: Antifoulant. Ref: H. Hirota, et al, Tetrahedron, 1998, 54, 13971 H

NC

HO

684 10-Isocyano-5-cadinen-4-ol Type: Cadinane sesquiterpene alkaloids. C16H25NO [α]D = +88.8° (c = 0.025, CHCl3). Source: Dorid nudibranch Phyllidia pustulosa (Japan waters). Pharm: Antifoulant. Ref: H. Hirota, et al, Tetrahedron, 1998, 54, 13971 H

HO

NC

256

9 Sesquiterpene and Sesterterpene Alkaloids

685 10-isothiocyanato-4,6-amorphadiene Type: Cadinane sesquiterpene alkaloids. C16H23NS Oil, [α]D = +74.4° (c = 9.8, CHCl3). Source: Sponge Axinyssa fenestratus (Fiji). Pharm: Anthelmintic. Ref: K. A. Alvi, et al, JNP, 1991, 54, 71 NCS

686 (–)-10-Isothiocyanato-4-amorphene Ca3 Type: Cadinane sesquiterpene alkaloids. C16H25NS [α]D = −63° (c = 7.4, CCl4). Source: Sponge Halichondria sp. (North coast of O’ahu, Hawaii), dorid nudibranches Phyllidia pustulosa (Yakushima I., Japan) and Phyllidiella pustulosa (Vietnam). Pharm: Antifoulant (larvae of acorn barnacle Balanus Amphitrite, IC50 = 0.70 μg/mL); antiplasmodial (Plasmodium falciparum strains K1 and NF 54, IC50 = 5.7 μmol/L). Ref: B. J. Burreson, et al, J. Chem. Soc., Chem. Commun. 1974, 1035│B. J. Burreson, et al, JACS, 1975, 97, 201│B. J. Burreson, et al, Tetrahedron, 1975, 31, 2015│T. Okino, et al, Tetrahedron, 1996, 52, 9447│E. G. Lyakhova,et al, Chem. Nat. Compd., 2010, 46, 534 NCS

H 4

1

10 7

H

687 4-Isothiocyanato-9-amorphene 4-Isothiocyanato-9-cadinene Type: Cadinane sesquiterpene alkaloids. C16H25NS Oil, [α]D = +111.7° (c = 2.5, CCl4). Source: Sponge Axinyssa fenestratus. Pharm: Anthelmintic. Ref: K. A. Alvi, et al, JNP, 1991, 54, 71 H SCN H

688 10-Isothiocyanatoamorph-5-en-4-ol Ca22 Type: Cadinane sesquiterpene alkaloids. C16H25NOS Oil. Source: Sponges Axinella fenestratus (Fiji), Topsentia sp. and Acanthella cavernosa (Thailand). Pharm: Anthelmintic. Ref: K. A. Alvi, et al, JNP, 1991, 54, 71

9.1 Sesquiterpene Alkaloids

257

NCS

H

HO

689 (+)-Axisonitrile 3 Sp2 Type: Spiroasane sesquiterpene alkaloids. C16H25N [α]D = +68.4° (CHCl3, c = 1). Source: Sponges Axinella cannabina (Bay of Taranto, Italy), Acanthella acuta (Mediterranean sea), Topsentia sp. (Thailand), Acanthella klethra (Pelorus Is., Queensland, Australia), Acanthella cf. cavernosa (Hachijo-jima I., Japan), Axinyssa aplysinoides (Mutok Harbor, Pohnpei I., Federated States of Micronesia), Acanthella cavernosa (Tani’s Reef, Gneerings Reef, Mooloolaba, Australia), Acanthella sp. (Yalong Bay, Hainan Province, China), dorid nudibranches Phyllidia ocellata (Hachijo-jima I., Japan), Phyllidia pustulosa (Yakushima/Kuchinoerabu-jima/Tenegashima Is., Japan) and Phyllidia ocellata (Mudjimba I., Mooloolaba, Australia). Pharm: Antiplasmodial (Plasmodium falciparum chloroquine-sensitive strain D6: IC50 = 142 ng/mL, chloroquine-resistant strain W2: IC50 = 16.5 ng/mL). Ref: B. Di Blasio, et al, Tetrahedron, 1976, 32, 473│J. C. Braekman, et al, Bull. Soc. Chim. Belg., 1987, 96, 539│K. A. Alvi, et al, JNP,1991, 54, 71│G. M. König, et al, JNP, 1992, 55, 633│H. Y. He, et al, JOC,1992, 57, 3191│N. Fusetani, et al, Tet. Lett., 1992, 33, 6823│T. Okino, et al, Tetrahedron, 1996, 52, 9447│P. Jumaryatno, et al, JNP, 2007, 70, 1725│J. -Z. Sun, et al, Arch. Pharmacal Res., 2009, 32, 1581│A. M. White, et al, JNP, 2015, 78, 1422

10

4

7 2

1

CN

690 (‒)-Axisonitrile 3 Sp6 Type: Spiroasane sesquiterpene alkaloids. C16H25N [α]D26 = ‒79° (CHCl3, c = 1.93). Source: Sponge Halichondria sp. (PP I., Andaman Sea, Southern Thailand). Pharm: Antifoulant (larvae of acorn barnacle Balanus Amphitrite, IC50 = 3.2 μg/mL). Ref: H. Prawat, et al, Tetrahedron, 2011, 67, 5651

10

4 2

1

CN

7

258

9 Sesquiterpene and Sesterterpene Alkaloids

691 10-epi-Axisonitrile 3 Sp8 Type: Spiroasane sesquiterpene alkaloids. C16H25N Source: Sponge Geodia exigua (Oshima, Kagoshima Prefecture, Japan), dorid nudibranch Phyllidia pustulosa (Yakushima/Kuchinoerabu-jima Is., Japan). Pharm: Antifoulant (larvae of acorn barnacle Balanus Amphitrite, IC50 = 10 μg/mL). Ref: T. Okino, et al, Tetrahedron, 1996, 52, 9447│ M. M. Uy, et al, Tetrahedron, 2003, 59, 731

10

4 2

1

7

CN

692 (+)-Axisothiocyanate 3 Sp3 Type: Spiroasane sesquiterpene alkaloids. C16H25NS [α]D = +165.2° (CHCl3, c = 1). Source: Sponges Axinella cannabina (Bay of Taranto, Italy), Acanthella klethra (Pelorus Is., Queensland, Australia), Acanthella cf. cavernosa (Hachijojima I., Japan), Acanthella cavernosa (Hachijo-jima I., Japan), Acanthella cavernosa (Tani’s Reef, Gneerings Reef, Mooloolaba, Australia), dorid nudibranch Phyllidia ocellata (Hachijo-jima I., Japan). Pharm: Antiplasmodial (Plasmodium falciparum chloroquine-sensitive strain D6: IC50 = 12,340 ng/mL, chloroquineresistant strain W2: IC50 = 3,110 ng/mL). Ref: B. Di Blasio, et al, Tetrahedron, 1976, 32, 473│G. M. König, et al, JNP, 1992, 55, 633│N. Fusetani, et al, Tet. Lett., 1992, 33, 6823│H. Hirota, et al, Tetrahedron, 1996, 52, 2359│P. Jumaryatno, et al, JNP, 2007, 70, 1725

10

4

7 2

1

SCN

693 Halochonadin F Ar11 Type: Aromadendrane sesquiterpene alkaloids. C15H27N Source: Sponge Halichondria sp. (Unten Port, Okinawa, Japan). Pharm: Antibacterial (Micrococcus luteus, MIC = 4 μg/mL); antifungal (Trichophyton mentagrophytes, MIC = 8 μg/mL); antibacterial (Cryptococcus neoformans, MIC = 16 μg/mL). Ref: H. Ishiyama, et al, JNP, 2008, 71, 1301

9.1 Sesquiterpene Alkaloids

259

H 2N H

H

694 (1R,4S,5S,6R,7S,10R)-(+)-Isothiocyanatoalloaromadendrane Ar9 Type: Aromadendrane sesquiterpene alkaloids. C16H25NS Oil, [α]D = +8° (c = 0.1, CHCl3). Source: Sponges Acanthella cavernosa (Hachijo-jima I., Japan) and Acanthella sp. (Yalong Bay, Hainan Province, China), nudibranch Phyllidiella pustulosa (Vietnam). Pharm: Antifoulant (larvae of acorn barnacle Balanus Amphitrite). Ref: H. Hirota, et al, Tetrahedron, 1996, 52, 2359│J. -Z. Sun, et al, Arch. Pharmacal Res., 2009, 32, 1581│E. G. Lyakhova, et al, Chem. Nat. Compd., 2010, 46, 534 SCN H

H

695 epi-Polasin B Axisothiocyanate 2; Ar4 Type: Aromadendrane sesquiterpene alkaloids. C16H25NS [α]D = +91.2° (c = 1.0, CHCl3) (epi-Polasin B); [α]D = +12.8° (c = 1.5, CHCl3) (Axisothiocyanate 2). Source: Sponges Acanthella cavernosa (Hachijo-jima I., Japan), Acanthella cavernosa (Tani’s Reef, Gneerings Reef, Mooloolaba, Australia), Axinella cannabina (Bay of Taranto, Italy), Axinyssa sp. (Tsutsumi I., Fukuoka prefecture, Japan), Axinyssa aplysinoides (Ant Atoll, Pohnpei I., Federated States of Micronesia) and Epipolasis kushimotoensis. Pharm: Antifoulant (larvae of acorn barnacle Balanus Amphitrite). Ref: E. Fattorusso, et al, Tetrahedron, 1974, 30, 3911│H. Tada, et al, CPB, 1985, 33, 1941│H. Y. He, et al, JOC, 1992, 57, 3191│H. Hirota, et al, Tetrahedron, 1996, 52, 2359│K. Kodama, et al, Org. Lett., 2003, 5, 169│P. Jumaryatno, et al, JNP, 2007, 70, 1725 NCS

H

H

260

9 Sesquiterpene and Sesterterpene Alkaloids

696 epi-Polasinthiourea B Epipolasinthiourea B Type: Aromadendrane sesquiterpene alkaloids. C24H36N2S Source: Sponge Epipolasis kushimotoensis. Pharm: Cytotoxic (L1210, ED50 = 3.7 μg/ mL). Ref: H. Tada, et al, CPB, 1985, 33, 1941

H N

S N H

H H

697 (+)-epi-Polasin A Ep5 Type: Epimaaliane sesquiterpene alkaloids. C16H25NS [α]D = +7.6° (c = 1, CHCl3). Source: Sponges Epipolasis kushimotoensis and Axinyssa aplysinoides (Ant Atoll, Pohnpei I., Federated States of Micronesia), sponge Axinella sp. (California). Pharm: Antiplasmodial (Plasmodium falciparum chloroquine-sensitive strain D6: IC50 = 5,600 ng/mL, chloroquine-resistant strain W2: IC50 = 5,550 ng/mL). Ref: J. E. Thompson, et al, Tetrahedron, 1982, 38, 1865│H. Tada, et al, CPB,1985, 33, 1941│H. Y. He, et al, JOC, 1992, 57, 3191

H

NCS

698 9-Isocyanopupukeanane Pu2 Type: Pupukeanane sesquiterpene alkaloids. C16H25N Oil. Source: Sponges Hymeniacidon sp. and Hymeniacidon sp., dorid nudibranches Phyllidia varicosa and Phyllidia sp. Pharm: Ichthyotoxin; antiplasmodial (Plasmodium falciparum, strain D6, IC50 = 2,520 ng/mL, strain W2, IC50 = 1,610 ng/mL, weak). Ref: B. J. Burreson, et al, JACS, 1975, 97, 4763│E. J. Corey, et al, JACS, 1979, 101, 1608│ M. R. Hagadone, et al,; H. Yamamoto, et al, JACS, 1979, 101,, p. 1609│E. Piers, Justus Liebigs Ann. Chem., 1982, 973│N. Fusetani, et al, Tet. Lett., 1990, 5623│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review)

9.1 Sesquiterpene Alkaloids

261

NC

H

699 9-epi-9-Isocyanopupukeanane Pu3 Type: Pupukeanane sesquiterpene alkaloids. C16H25N Oil, [α]D = +31° (c = 0.048, CHCl3). Source: Dorid nudibranches Phyllidia bourguini and Phyllidia pustulosa. Pharm: Ichthyotoxic; antifungal. Ref: M. R. Hagadone, et al, Helv. Chim. Acta, 1979, 62, 2484│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review) H

NC 9

700 2-Isocyanopupukeanane Pu7 Type: Pupukeanane sesquiterpene alkaloids. C16H25N Crystal (MeOH aq), mp 81–82 °C. Source: Sponge Hymeniacidon sp. (Hawaii), dorid nudibranch Phyllidia varicosa (Pupukea, north shore of O’ahu, Hawaii). Pharm: Ichthyotoxin. Ref: M. R. Hagadone, et al, Helv. Chim. Acta, 1979, 62, 2484│E. J. Corey, et al, Tet. Lett., 1979, 2745│G. Frater, et al, Helv. Chim. Acta, 1984, 67, 1702

CN

701 (–)-9-Isothiocyanatopupukaenane Type: Pupukeanane sesquiterpene alkaloids. C16H25NS Source: Sponge Axinyssa sp. (Great Barrier Reef, 146°50´E 18°00´S). Pharm: Cytotoxic (KB, IC50 > 20000 ng/mL), antiplasmodial (Plasmodium falciparum, clones D6, IC50 = 2520 ng/mL, Plasmodium falciparum, clones W2, IC50 = 1610 ng/mL). Ref: J. S. Simpson, et al, Aust. J. Chem., 1997, 50, 1123

262

9 Sesquiterpene and Sesterterpene Alkaloids

SCN

702 9-Isothiocyanatopupukeanane Pu4 Type: Pupukeanane sesquiterpene alkaloids. C16H25NS Source: Sponge Axinyssa sp. nov. (Great Barrier Reef). Pharm: Antiplasmodial (Plasmodium falciparum, strain D6, IC50 = 3,290 ng/mL, strain W2, IC50 = 890 ng/mL). Ref: J. S. Simpson, et al, Aust. J. Chem., 1997, 50, 1123

SCN H

703 2-Thiocyanatoneopupukaenane Type: Pupukeanane sesquiterpene alkaloids. C16H25NS Oil, [α]D = −71.5° (c = 0.5, CHCl3) (−31°). Source: Sponges Phycopsis terpnis (Okinawa), Axinyssa aplysinoides and an unidentified sponge. Pharm: Antifoulant (larval settlement inhibitor); crustacean metamorphosis inhibitor. Ref: A. T. Pham, et al, Tet. Lett., 1991, 32, 4843│H. -Y. He, et al, JOC, 1992, 57, 3191│J. S. Simpson, et al, Aust. J. Chem., 1997, 50, 1123

S N

704 2-Thiocyanatoneopupukeanane Pu12 Type: Pupukeanane sesquiterpene alkaloids. C16H25NS Source: Sponges Phycopsis terpnis (Okinawa, Japan and Pohnpei) and Axinyssa aplysinoides (Mutok Harbor, Pohnpei I., Federated States of Micronesia), dorid nudibranch Phyllidia pustulosa (Kuchinoerabu/Tanegoshima I., Japan). Pharm: Antiplasmodial (Plasmodium falciparum, strain D6, IC50 = 4,700 ng/mL, strain W2, IC50 = 890 ng/mL). Ref: A. T. Pham, et al, Tet. Lett., 1991, 32, 4843│H. Y. He, et al, JOC, 1992, 57, 3191│T. Okino, et al, Tetrahedron, 1996, 52, 9447

9.1 Sesquiterpene Alkaloids

263

9 7 1

H

4 2

S

N

705 9-Thiocyanatopupukeanane Pu5 Type: Pupukeanane sesquiterpene alkaloids. C16H25NS Source: Dorid nudibranch Phyllidia varicosa and its sponge-prey Axinyssa aculeata (Pramuka I., Indonesia), nudibranch Phyllidiella pustulosa (Vietnam). Pharm: Antifoulant (larvae of acorn barnacle Balanus Amphitrite, IC50 = 4.6 μg/mL). Ref: Y. Yasman, et al, JNP, 2003, 66, 1512│E. G. Lyakhova, et al, Chem. Nat. Compd., 2010, 46, 534

N

S H

706 9-epi-Thiocyanatopupukeanane Pu6 Type: Pupukeanane sesquiterpene alkaloids. C16H25NS Source: Dorid nudibranch Phyllidia varicosa and its sponge-prey Axinyssa aculeata (Pramuka I., Indonesia), dorid nudibranch Phyllidiella pustulosa (Vietnam). Pharm: Antifoulant (larvae of acorn barnacle Balanus Amphitrite, IC50 = 2.3 μg/mL). Ref: Y. Yasman, et al, JNP, 2003, 66, 1512│E. G. Lyakhova, et al, Chem. Nat. Compd., 2010, 46, 534

H S N

707 3-Isocyanotheonellin Bi2 Type: Bisabolane sesquiterpene alkaloids. C16H25N Source: Sponges Lipastrotethya ana (Lingshui Bay, Hainan) and Raphoxya sp. (Blue Hole, Guam), dorid nudibranches Phyllidia sp. (Colombo, Sri Lanka), Phyllidia pustulosa (Hachijo-jima I., Japan) and Phyllidiella pustulosa (Hainan I., South China Sea). Pharm: Antifoulant (larvae of the

264

9 Sesquiterpene and Sesterterpene Alkaloids

acorn barnacle Balanus Amphitrite, IC50 = 0.13 μg/mL, potent). Ref: N. K. Gulavita, et al, JOC, 1986, 51, 5136│N. Fusetani, et al, Tet. Lett., 1991, 32, 7291│E. Manzo, et al, JNP,2004, 67, 1701│S. -C. Mao, et al, Tetrahedron, 2007, 63, 11108│A. D. Wright, et al, JNP, 2012, 75, 502│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review)

7

11

1

CN

3

5

H

708 Axinyssimide A Type: Farnesane sesquiterpene slkaloids C16H24Cl3NO [α]D = +1.7° (c = 0.06, CHCl3). Source: Sponge Axinyssa sp. Pharm: Antifoulant (cypris larvae of barnacle Balanus amphitrite). Ref: H. Hirota, et al, Tetrahedron, 1998, 54, 13971 Cl N

Cl

O Cl

709 Axinyssimide B Type: Farnesane sesquiterpene slkaloids C16H26Cl3NO2 [α]D = −22.5° (c = 0.02, CHCl3). Source: Sponge Axinyssa sp. Pharm: Antifoulant (cypris larvae of barnacle Balanus amphitrite). Ref: H. Hirota, et al, Tetrahedron, 1998, 54, 13971 Cl

HO 10

N

Cl

Cl

OH

710 Axinyssimide C Type: Farnesane sesquiterpene slkaloids C16H26Cl3NO2 [α]D = +7.3° (c = 0.015, CHCl3). Source: Sponge Axinyssa sp. Pharm: Antifoulant (cypris larvae of barnacle Balanus amphitrite). Ref: H. Hirota, et al, Tetrahedron, 1998, 54, 13971 Cl

HO 10

N 10-epimer of Axinyssimide B

OH

Cl

Cl

711 Farneside A Type: Farnesane sesquiterpene slkaloids C24H38N2O7 Source: Marine-derived streptomycete Streptomyces sp. (sediment, Nacula I., Yasawa I., Fiji). Pharm:

9.1 Sesquiterpene Alkaloids

265

Antiplasmodial (Plasmodium falciparum, modest). Ref: E. Z. Ilan, et al, JNP, 2013, 76, 1815 O

O

O O

NH

N O

HO

OH

712 Oceanapamine Type: Farnesane sesquiterpene slkaloids C20H33N3 Oil (trifluoroacetate), [α]D22 = −6.4° (c = 3.1, MeOH) (trifluoroaceta). Source: Sponge Oceanapia sp. (Philippines). Pharm: Antibacterial (Bacillus subtilis and Escherichia coli, 25 μg/disk, Pseudomonas aeruginosa, 100 μg/disk, Staphylococcus aureus 50 μg/disk); antifungal (Candida albicans, 50 μg/disk). Ref: K. G. Boyd, et al, JNP, 1995, 58, 302 H 2N

H N N

713 Drimentine G Type: Miscellaneous bicyclic sesquiterpene alkaloids. C32H44N2O2 Source: Marinederived streptomycete Streptomyces sp. CHQ-64. Pharm: Cytotoxic (HCT8, IC50 = 2.81 μmol/L, Bel7402, IC50 = 1.38 μmol/L, A549, IC50 = 1.01 μmol/L, A2780, IC50 = 2.54 μmol/L); topoisomerase I inhibitor (weak). Ref: Q. Che, et al, Org. Lett., 2012, 14, 3438│Q. Che, et al, JNP, 2013, 76, 759 H N

O

H

NH H

O

H

714 Indosespene Type: Miscellaneous bicyclic sesquiterpene alkaloids. C23H29NO3 Source: Mangrovederived 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

266

9 Sesquiterpene and Sesterterpene Alkaloids

OH O H

H OH

N H

715 3’-Methylaminoavarone Type: Miscellaneous bicyclic sesquiterpene alkaloids. C22H31NO2 Red cryst., mp 153–155 °C. Source: Sponge Dysidea avara. Pharm: Cell division inhibitor (sea urchin eggs). Ref: K. A. Alvi, et al, JOC, 1992, 57, 6604│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev) HN O

O

4

12

716 4ʹ-Methylaminoavarone Type: Miscellaneous bicyclic sesquiterpene alkaloids. C22H31NO2 Red cryst., mp 160–163 °C. Source: Sponge Dysidea avara. Pharm: Cytotoxic (melanoma Fem-X, IC50 = 2.4 μmol/L; normal lymphocytes, inactive); cell division inhibitor (sea urchin eggs); antimicrobial; antimutagenic; antimitotic. Ref: G. Cimino, et al, Experientia, 1982, 38, 896│R. Puliti, et al, Acta Crystallogr., Sect. C, 1998, 54, 1954│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)

O

H N

O

4

12

717 Nakijinol B diacetate Type: Miscellaneous bicyclic sesquiterpene alkaloids. C26H33NO5 Source: Sponge Dactylospongia elegans (Pugh Shoal, Northern Territory, Australia). Pharm: Cytotoxic (SF268, GI50 = 9.0 μmol/L; MCF7, GI50 = 19 μmol/L; H460, GI50 = 6.8 μmol/L; HT29,

9.1 Sesquiterpene Alkaloids

267

GI50 = 15 μmol/L; CHO-K1, GI50 = 5.2 μmol/L). Ref: S. P. B. Ovenden, et al, JNP, 2011, 74, 65 O O

O O

N H

O

718 Nakijiquinone A Type: Miscellaneous bicyclic sesquiterpene alkaloids. C23H31NO5 Red solid, mp 156–158 °C, [α]D20 = −71.7° (c = 1, MeOH). Source: An unidentified sponge (family Spongiidae, Okinawa). Pharm: Cytotoxic (L1210, IC50 = 3.8 μg/mL; KB, IC50 = 7.6 μg/ mL); c-erbB-2 kinase inhibitor (IC50 = 30 μg/mL); PKC inhibitor (IC50 = 270 μg/mL); inhibitors of variety of kinases (EGFR, IC50 > 400 μg/mL; tyrosine kinase VEGFR2). Ref: H. Shigemori, et al, Tetrahedron, 1994, 50, 8347│J. Kobayashi, et al, Tetrahedron, 1995, 51, 10867│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)│D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) OH

HN O

O

O H

OH

4

11

719 Nakijiquinone B Type: Miscellaneous bicyclic sesquiterpene alkaloids. C26H37NO5 Red solid, [α]D20 = −282.3° (c = 0.13, CHCl3). Source: An unidentified sponge (family Spongiidae, Okinawa). Pharm: Cytotoxic (L1210, IC50 = 2.8 μg/mL; KB, IC50 = 5.0 μg/mL); c-erbB-2 kinase inhibitor (IC50 = 95 μg/mL); PKC inhibitor (IC50 = 200 μg/mL); inhibitors of variety of kinases (EGFR, IC50 = 250 μg/mL; tyrosine kinase VEGFR2). Ref: H. Shigemori, et al, Tetrahedron, 1994, 50, 8347│J. Kobayashi, et al, Tetrahedron, 1995, 51, 10867│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)│D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev)

268

9 Sesquiterpene and Sesterterpene Alkaloids

HN

OH S

O

O

O H

OH

720 Nakijiquinone C Type: Miscellaneous bicyclic sesquiterpene alkaloids. C24H33NO6 Red amorph. solid, mp 198–200 °C, [α]D20 = −73° (c = 0.03, EtOH). Source: An unidentified sponge (family Spongiidae, Okinawa). Pharm: Cytotoxic (L1210, IC50 = 5.8 μg/mL, KB, IC50 = 6.2 μg/mL); c-erbB-2 kinase inhibitor (IC50 = 26 μmol/L); kinase PKC inhibitor (IC50 = 23 μmol/L); inhibitors of variety of kinases (EGFR, kinase c-erbB-2, tyrosine kinase VEGFR2); selectively inhibits Her-2/Neu protooncogene; EGFR kinase inhibitor (IC50 = 170 μg/mL). Ref: J. Kobayashi, et al, Tetrahedron, 1995, 51, 10867│J. Kobayashi, et al, Tet. Lett., 1995, 36, 5589│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)│D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) OH OH

HN O

O

O H

OH

721 Nakijiquinone D Type: Miscellaneous bicyclic sesquiterpene alkaloids. C25H35NO6 Red amorph. solid, mp 188–191 °C, [α]D20 = −172° (c = 0.2, EtOH). Source: An unidentified sponge (family Spongiidae, Okinawa). Pharm: Cytotoxic (L1210, IC50 = 8.1 μg/mL; KB, IC50 = 1.2 μg/ mL); c-erbB-2 kinase inhibitor (IC50 = 29 μg/mL); PKC inhibitor (IC50 = 220 μg/mL); inhibitors of variety of kinases (EGFR, IC50 > 400 μg/mL; tyrosine kinase VEGFR2). Ref: J. Kobayashi, et al, Tetrahedron, 1995, 51, 10867│J. Kobayashi, et al, Tet. Lett.,

9.1 Sesquiterpene Alkaloids

269

1995, 36, 5589│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)│D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) OH OH HN O

O

O H

OH

722 Nakijiquinone G Type: Miscellaneous bicyclic sesquiterpene alkaloids. C26H35N3O3 Amorph. red solid, [α]D24 = +109° (c = 0.25, MeOH). Source: An unidentified sponge (family Spongiidae, Okinawa). Pharm: Cytotoxic (P388, L1210, KB, IC50 = 2.4 μg/mL to > 10 μg/mL, kinase HER2 inhibitor). Ref: Y. Takahashi, et al, BoMC, 2008, 16, 7561│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)│D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) N NH HN

O

O HO H 4

11

723 Nakijiquinone H Type: Miscellaneous bicyclic sesquiterpene alkaloids. C26H40N4O3 Amorph. red solid, [α]D22 = +66° (c = 0.25, MeOH). Source: An unidentified sponge (family Spongiidae, Okinawa). Pharm: Cytotoxic (P388, L1210, KB, IC50 = 2.4 μg/mL to > 10 μg/mL, kinase HER2 inhibitor). Ref: Y. Takahashi, et al, BoMC, 2008, 16, 7561│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)│D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev)

270

9 Sesquiterpene and Sesterterpene Alkaloids

H N

HN

NH2 NH

O

O HO H 4

11

724 Nakijiquinone I Type: Miscellaneous bicyclic sesquiterpene alkaloids. C25H37NO4S Amorph. red solid, [α]D24 = +158° (c = 0.25, MeOH). Source: An unidentified sponge (family Spongiidae, Okinawa). Pharm: Cytotoxic (P388, L1210, KB, IC50 = 2.4 μg/mL to > 10 μg/mL, kinase HER2 inhibitor). Ref: Y. Takahashi, et al, BoMC, 2008, 16, 7561│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)│D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev) HN

S O

O

O HO H

4

11

725 Nakijiquinone N Type: Miscellaneous bicyclic sesquiterpene alkaloids. C26H39NO3 Purple–red amorph. solid, [α]D21 = +124° (c = 0.25, CHCl3). Source: An unidentified sponge (family Spongiidae, Okinawa). Pharm: HER2 tyrosine kinase inhibitor (1 mmol/L, InRt = 66%). Ref: Y. Takahashi, et al, JNP, 2010, 73, 467│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)

9.1 Sesquiterpene Alkaloids

271

HN O

O H

OH

4

11

726 Nakijiquinone O Type: Miscellaneous bicyclic sesquiterpene alkaloids. C25H37NO3 Purple–red amorph. solid, [α]D23 = +160° (c = 1, CHCl3). Source: An unidentified sponge (family Spongiidae, Okinawa). Pharm: HER2 tyrosine kinase inhibitor (1 mmol/L, InRt = 59%). Ref: Y. Takahashi, et al, JNP, 2010, 73, 467│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev) HN O

O H

OH

4

11

727 Nakijiquinone P Type: Miscellaneous bicyclic sesquiterpene alkaloids. C29H37NO3 Purple–red amorph. solid, [α]D21 = −14° (c = 0.2, CHCl3). Source: An unidentified sponge (family Spongiidae, Okinawa). Pharm: EGFR tyrosine kinase inhibitor (1 mmol/L, InRt = 76%). Ref: Y. Takahashi, et al, JNP, 2010, 73, 467│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)

272

9 Sesquiterpene and Sesterterpene Alkaloids

HN O

O H

OH

728 Nakijiquinone R Type: Miscellaneous bicyclic sesquiterpene alkaloids. C23H33NO6S Purple–red amorph. solid, [α]D22 = +38° (c = 0.2, CHCl3). Source: An unidentified sponge (family Spongiidae, Okinawa). Pharm: EGFR tyrosine kinase inhibitor (1 mmol/L, InRt = 99%); HER2 tyrosine kinase inhibitor (1 mmol/L, InRt = 52%). Ref: Y. Takahashi, et al, JNP, 2010, 73, 467│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev) O S HN

OH

O

O

O H

OH

4

11

729 Reticulidin A Type: Miscellaneous bicyclic sesquiterpene alkaloids. C16H22Cl3NO Glass, [α]D26 = +11 ° (c = 0.32, CHCl3). Source: Dorid nudibranch Reticulidia fungia (Okinawa). Pharm: Cytotoxic (KB, IC50 = 0.41 μg/mL, L1210, IC50 = 0.59 μg/mL). Ref: J. Tanaka, et al, JNP, 1999, 62, 1339 HO

Cl

N

Cl Cl

H

9.1 Sesquiterpene Alkaloids

273

730 Reticulidin B Type: Miscellaneous bicyclic sesquiterpene alkaloids. C16H22Cl3NO Glass, [α]D26 = −26° (c = 0.092, CHCl3). Source: Nudibranch Reticulidia fungia (Okinawa). Pharm: Cytotoxic (KB, IC50 = 0.42 μg/mL, L1210, IC50 = 0.11 μg/mL). Ref: J. Tanaka, et al, JNP, 1999, 62, 1339 HO

N

Cl Cl

Cl

H

731 Smenospongiarine Type: Miscellaneous bicyclic sesquiterpene alkaloids. C26H39NO3 Cryst., mp 170–172 ° C. Source: Sponges Spongia sp. (Australia), Smenospongia sp., Hippospongia sp. and Dactylospongia elegans. Pharm: Immune system activity (IL-8 release enhancer, IC50 (apparent) > 1 μg/mL); cytotoxic (L1210, IC50 = 4.0 μg/mL); antimicrobial. Ref: T. Oda, et al, J. Nat. Med., 2007, 61, 434│S. Aoki, et al, CPB, 2004, 52, 935│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev) O HO

NH H

O 10

4

5

11

732 5-epi-Smenospongiarine Type: Miscellaneous bicyclic sesquiterpene alkaloids. C26H39NO3 Oil, [α]D = +96.7° (c = 0.12, CHCl3). Source: Sponges Dysidea elegans (Papua New Guinea and Thailand) and Dactylospongia elegans. Pharm: Cytotoxic (in vitro: A549, IC50 = 0.8 μg/mL; HT29, IC50 = 0.9 μg/mL; B16/F10, IC50 = 0.6 μg/mL; P388, IC50 = 0.7 μg/mL). Ref: J. Rodriguez, et al, Tetrahedron, 1992, 48, 6667│S. Aoki, et al, CPB, 2004, 52, 935│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)

274

9 Sesquiterpene and Sesterterpene Alkaloids

O HO

NH H

O 10 5

4

11

733 Smenospongidine Type: Miscellaneous bicyclic sesquiterpene alkaloids. C29H37NO3 Cryst. (MeOH), mp 168–170 °C. Source: Sponges Smenospongia sp., Hippospongia sp. and Dactylospongia elegans. Pharm: Cytotoxic (differentiation-inducing activity to K562 cells into erythroblast, lowest effective concentration = 2 μmol/L); antimicrobial; immune system activity (IL-8 release enhancer, IC50 (apparent) > 1 μg/mL). Ref: T. Oda, et al, J. Nat. Med., 2007, 61, 434│N. K. Utkina, et al, Khim. Prir. Soedin., 1990, 26, 47; Chem. Nat. Compd. (Engl. Transl.), 37│S. Aoki, et al, CPB, 2004, 52, 935│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev) O HO

H

O

N H

10 5

734 5-epi-Smenospongidine Type: Miscellaneous bicyclic sesquiterpene alkaloids. C29H37NO3 Oil, [α]D = +37.5° (c = 0.16, CHCl3). Source: Sponges Dysidea elegans (Papua New Guinea and Thailand) and Dactylospongia elegans. Pharm: Cytotoxic (differentiation-inducing activity to K562 cells into erythroblast, lowest effective concentration = 2 μmol/L); cytotoxic (in vitro: A549, IC50 = 3.9 μg/mL; HT29, IC50 = 2.4 μg/mL; B16/F10, IC50 = 1.9 μg/mL; P388, IC50 = 1.9 μg/mL). Ref: J. Rodriguez, et al, Tetrahedron, 1992, 48, 6667│S. Aoki, et al, CPB, 2004, 52, 935│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)

9.1 Sesquiterpene Alkaloids

275

HN O

O

H

OH 5

735 Smenospongine Type: Miscellaneous bicyclic sesquiterpene alkaloids. C21H29NO3 Red cryst., mp 153–155 °C. Source: Sponges Smenospongia sp., Hippospongia sp., Dactylospongia elegans and Petrosaspongia metachromia. Pharm: Cytotoxic (differentiation-inducing activity to K562 cells into erythroblast, lowest effective concentration = 2 μmol/L); cytotoxic (L1210 cell lines, IC50 = 1 μg/mL); antimicrobial; immune system activity (IL-8 release enhancer, IC50 (apparent) > 1 μg/mL). Ref: T. Oda, et al, J. Nat. Med., 2007, 61, 434│S. Aoki, et al, CPB, 2004, 52, 935│ M. -L. Kondracki, et al, Tetrahedron, 1989, 45, 1995│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev) O HO

NH2 H 4

O 10 5

11

736 5-epi-Smenospongine Type: Miscellaneous bicyclic sesquiterpene alkaloids. C21H29NO3 Purple powder, [α]D23 = +73.1 (c = 0.03, CHCl3). Source: Sponges Petrosaspongia metachromia and Dactylospongia elegans. Pharm: Cytotoxic (differentiation-inducing activity to K562 cells into erythroblast, lowest effective concentration = 2 μmol/L). Ref: J. H. Kwak, et al, JNP, 2000, 63, 1153│S. Aoki, et al, CPB, 2004, 52, 935

276

9 Sesquiterpene and Sesterterpene Alkaloids

O HO

NH2 H

O 10 5

4

11

737 Smenospongine B Glycinylilimaquinone Type: Miscellaneous bicyclic sesquiterpene alkaloids. C23H31NO5 Amorph. red powder. Source: Sponges Dactylospongia elegans (Pugh Shoal, Northern Territory, Australia) and Fasciospongia sp. (Philippines). Pharm: Cytotoxic (SF268, GI50 = 9.7 μmol/L; MCF7, GI50 = 10 μmol/L; H460, GI50 = 6.0 μmol/L; HT29, GI50 = 6.0 μmol/L; CHO-K1, GI50 = 3.0 μmol/L); cytotoxic (HT29 cell lines, IC50 = 7.8 μg/ mL). Ref: T. P. Evans, et al, Nat. Prod. Lett., 1994, 4, 287│S. Aoki, et al, CPB, 2004, 52, 935│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev)│S. P. B. Ovenden, et al, JNP, 2011, 74, 65 O HO

H

O

N H

OH O

738 Smenospongine C Type: Miscellaneous bicyclic sesquiterpene alkaloids. C24H33NO5 Source: Sponge Dactylospongia elegans (Pugh Shoal, Northern Territory, Australia). Pharm: Cytotoxic (SF268, GI50 = 20 μmol/L; MCF7, GI50 = 31 μmol/L; H460, GI50 = 14 μmol/L; HT29, GI50 = 28 μmol/L; CHO-K1, GI50 = 18 μmol/L). Ref: S. P. B. Ovenden, et al, JNP, 2011, 74, 65 O HO

H

O

O

N H

OH

9.1 Sesquiterpene Alkaloids

277

739 Smenospongorine Type: Miscellaneous bicyclic sesquiterpene alkaloids. C25H37NO3 Source: Sponges Smenospongia sp. and Dactylospongia elegans. Pharm: Cytotoxic (differentiationinducing activity to K562 cells into erythroblast, lowest effective concentration = 2 μmol/L); antimicrobial. Ref: M. -L. Kondracki, et al, Tetrahedron, 1989, 45, 1995│S. Aoki, et al, CPB, 2004, 52, 935│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev) O HO

NH H

O 10 5

4

11

740 5-epi-Smenospongorine Type: Miscellaneous bicyclic sesquiterpene alkaloids. C25H37NO3 [α]D = +23° (c = 0.06, CHCl3). Source: Sponge Dactylospongia elegans. Pharm: Cytotoxic (differentiation-inducing activity to K562 cells into erythroblast, lowest effective concentration = 2 μmol/L). Ref: S. Aoki, et al, CPB, 2004, 52, 935│ M. Gordaliza, et al, Mar. Drugs, 2010, 8, 2849 (rev) O HO

NH H 4

O 10 5

11

741 Trikendiol Type: Miscellaneous bicyclic sesquiterpene alkaloids. C38H46N2O4 Red crystals (Me2CO), mp 160–162 °C, [α]D = +102° (c = 0.02, CHCl3). Source: Sponge Trikentrion loeve (Senegal). Pharm: Anti-HIV (CEM-4 HIV-1 infection assay, IC50 = 1.0 μg/mL); red pigment. Ref: A. Loukaci, et al, Tet. Lett., 1994, 35, 6869

278

9 Sesquiterpene and Sesterterpene Alkaloids

OH O HN NH O OH

742 (‒)-(1S,2R,5S,8R)-2-Isocyanoclovane Fu13 Type: Other sesquiterpenoids alkaloids. C16H25N Source: Dorid nudibranch Phyllidia ocellata (Mudjimba I., Mooloolaba, Australia). Pharm: Antimalarial Ref: A. M. White, et al, JNP, 2015, 78, 1422│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review)

H CN

743 (‒)-(1S,5S,8R)-2-Isocyanoclovene Fu12 Type: Other sesquiterpenoids alkaloids. C16H23N Source: Dorid nudibranch Phyllidia ocellata (Mudjimba I., Mooloolaba, Australia). Pharm: Antimalarial Ref: A. M. White, et al, JNP, 2015, 78, 1422│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review)

H

CN

744 2-Isocyanotrachyopsane Fu1 Type: Other sesquiterpenoids alkaloids. C16H25N Source: Dorid nudibranch Phyllidia varicosa (Shimokoshiki I., Japan). Pharm: Antifoulant (larvae of the acorn barnacle Balanus Amphitrite, IC50 = 0.33 μg/mL). Ref: T. Okino, Eet al, Tetrahedron 1996, 52, 9447│J. Emsermann, et al, Mar. Drugs, 2016, 14, 16 (review)

9.2 Sesterterpene Alkaloids

279

CN

745 Sespenine Type: Other sesquiterpenoids alkaloids. C23H29NO4 Source: Mangrove-derived streptomycete Streptomyces sp. (endophytic) from mangrove Kandelia candel (stem). Pharm: Antibacterial (MRSA and VREF). Ref: L. Ding, et al, Org. Biomol. Chem., 2011, 9, 4029 O OH HO H H

O N H

H

9.2 Sesterterpene Alkaloids 746 Coscinolactam A Type: Sesterterpene alkaloids. C27H41NO7S Amorph. solid, [α]D25 = +25.7° (c = 0.07, MeOH). Source: Sponge Coscinoderma mathewsi (Vangunu I., Solomon Is.). Pharm: Anti-inflammatory (moderate); PGE2 inhibitor; NO production inhibitor. Ref: S. De Marino, et al, Tetrahedron, 2009, 65, 2905 O OH S O

O

H H

O

N COOH

280

9 Sesquiterpene and Sesterterpene Alkaloids

747 Coscinolactam B Type: Sesterterpene alkaloids. C27H41NO7S Amorph. solid, [α]D25 = +8.6° (c = 0.07, MeOH). Source: Sponge Coscinoderma mathewsi (Vangunu I., Solomon Is.). Pharm: Anti-inflammatory (moderate); PGE2 inhibitor; NO production inhibitor. Ref: S. De Marino, et al, Tetrahedron, 2009, 65, 2905 O OH S O

O

O

H N H

COOH

748 Fasciospongine A Type: Sesterterpene alkaloids. C30H47N3O5S Oil, [α]D23 = −51.5° (c = 0.26, MeOH). Source: Sponge Fasciospongia sp. (Palau, Oceania). Pharm: Antibacterial (Streptomyces sp. 85E, growth and gporulation inhibitor, 20 μg/disk, IZD = 18 mm, 10 μg/disk, IZD = 16 mm, 5 μg/disk, IZD = 14 mm, 2.5 μg/disk, inactive). Ref: G. Yao, et al, JNP, 2009, 72, 319│G. Yao, et al, Org. Lett., 2007, 9, 3037 O HO O

S O H

5

O

2

N

H N N H

749 Fasciospongine B Type: Sesterterpene alkaloids. C30H47N3O5S Oil, [α]D23 = −52.4° (c = 0.25, MeOH). Source: Sponge Fasciospongia sp. (Palau, Oceania). Pharm: Antibacterial (Streptomyces sp. 85E, growth and gporulation inhibitor, 20 μg/disk, IZD = 19 mm, 10 μg/disk, IZD = 17 mm, 5 μg/disk, IZD = 15 mm, 2.5 μg/disk, inactive). Ref: G. Yao, et al, JNP, 2009, 72, 319│G. Yao, et al, Org. Lett., 2007, 9, 3037

9.2 Sesterterpene Alkaloids

281

O HO O

S O H

5

2

O

N

H N N H

750 Fasciospongine C Type: Sesterterpene alkaloids. C30H52N4O5S Oil, [α]D25 = −51.7° (c = 0.11, MeOH). Source: Sponge Fasciospongia sp. (Palau, Oceania). Pharm: Antibacterial (Streptomyces sp. 85E, growth and gporulation inhibitor, 20 μg/disk, IZD = 14 mm, 10 μg/disk, IZD = 13 mm, 5 μg/disk, inactive). Ref: G. Yao, et al, JNP, 2009, 72, 319 O HO S O

O

O

H2N NH

N

N H

H

751 Hippolide A Type: Sesterterpene alkaloids. C25H37NO4 Source: Sponge Hippospongia lachne (Yongxing I., China). Pharm: Protein tyrosine phosphatase 1B inhibitor (negative regulator of insulin signal transduction). Ref: S. -J. Piao, et al, JNP, 2011, 74, 1248

H HO

O

O O

N H

752 Irregularasulfate Type: Sesterterpene alkaloids. C30H51NO5S Glass, [α]D = +39.8° (c = 0.4, MeOH). Source: Sponge Spongia irregularis (Papua New Guinea). Pharm: Calcineurin inhibitor (IC50 = 59 μmol/L). Ref: G. Carr, et al, JNP, 2007, 70, 1812

282

9 Sesquiterpene and Sesterterpene Alkaloids

O

O HO

S

O

O

N

H

753 Kimbasine A Type: Sesterterpene alkaloids. C29H45NO5 Source: Sponge Igernella notabilis. Pharm: Cytotoxic (differential inhibition toward repair deficient lines, particularly ret A-(recombinationless) strains GW801, GW802, GW803 and AB/886); antibacterial (Staphylococcus aureus, 100 μg/disk, IZD = 7.5 mm); phytotoxic (johnsongrass, 100 μg/mL). Ref: J. H. Cardellina, et al, Tet. Lett., 1991, 32, 2347 O O H

N H

O

O O

754 Kimbasine B Type: Sesterterpene alkaloids. C27H41NO5 [α]D = −64.1° (c = 0.1, CHCl3). Source: Sponge Igernella notabilis. Pharm: Cytotoxic. Ref: J. H. Cardellina, et al, Tet. Lett., 1991, 32, 2347 O

H

O

N O H

O O

755 19-Oxofasciospongine A Type: Sesterterpene alkaloids. C30H44N3O6S Oil, [α]D25 = −42.2° (c = 0.25, MeOH). Source: Sponge Fasciospongia sp. (Palau, Oceania). Pharm: Antibacterial (Streptomyces

9.2 Sesterterpene Alkaloids

283

sp. 85E, growth and gporulation inhibitor, 20 μg/disk, IZD = 25 mm, 10 μg/disk, IZD = 20 mm, 5 μg/disk, IZD = 16 mm, 2.5 μg/disk, IZD = 14 mm). Ref: G. Yao, et al, JNP, 2009, 72, 319

HO O

O S O

N O H

H N

O N

10 Steroidal and Miscellaneous Alkaloids 10.1 Steroidal Alkaloids 756 Cortistatin A Type: Buxus. C30H36N2O3 [α]D20 = +30.1° (c = 0.56, MeOH). Source: Sponge Corticium simplex. Pharm: Anti-angiogenic (HUVECs, IC50 = 0.0018 μmol/L, SI (= IC50 of testing cells/IC50 of HUVECs) = 1; KB (KB-3-1), IC50 = 7.0 μmol/L, SI = 3900; neuro-2a, IC50 = 6.0 μmol/L, SI = 3300; K562, IC50 = 7.0 μmol/L, SI = 3900; NHDF, IC50 = 6.0 μmol/L, SI = 3300; control Doxorubicin with no selectivity: HUVECs, IC50 = 5.1 nmol/L; KB-3-1, SI = 4.1; K562, SI = 3.5; neuro-2a, SI = 5.5; NHDF, SI = 1.9). Ref: S. Aoki, et al, JACS, 2006, 128, 3148│C. FNising, et al, Angew. Chem., Int. Ed., 2008, 47, 9389

H OH

N 17 16

HO O

H

N

757 Cortistatin B Type: Buxus. C30H36N2O4 [α]D20 = +15.6° (c = 0.27, MeOH). Source: Sponge Corticium simplex. Pharm: Anti-angiogenic (HUVECs, IC50 = 1.1 μmol/L, SI (= IC50 of testing cells/IC50 of HUVECs) = 1; KB (KB-3-1), IC50 = 120 μmol/L, SI = 110; neuro-2a, IC50 = 160 μmol/L, SI = 150; K562, IC50 = 200 μmol/L, SI = 180; NHDF, IC50 > 300 μmol/L; control Doxorubicin with no selectivity: HUVECs, IC50 = 5.1 nmol/L; KB-3-1, SI = 4.1; K562, SI = 3.5; neuro-2a, SI = 5.5; NHDF, SI = 1.9). Ref: S. Aoki, et al, JACS, 2006, 128, 3148│C. FNising, et al, Angew. Chem., Int. Ed., 2008, 47, 9389

H N 17

OH 16

HO O

OH

H

N

https://doi.org/10.1515/9783110653908-007

286

10 Steroidal and Miscellaneous Alkaloids

758 Cortistatin C Type: Buxus. C30H34N2O4 [α]D20 = −45° (c = 0.71, MeOH). Source: Sponge Corticium simplex. Pharm: Anti-angiogenic (HUVECs, IC50 = 0.019 μmol/L, SI (= IC50 of testing cells/IC50 of HUVECs) = 1; KB (KB-3-1), IC50 = 150 μmol/L, SI = 7900; neuro-2a, IC50 = 180 μmol/L, SI = 9500; K562, IC50 > 300 μmol/L; NHDF, IC50 > 300 μmol/L; control Doxorubicin with no selectivity: HUVECs, IC50 = 5.1 nmol/L; KB-3-1, SI = 4.1; K562, SI = 3.5; neuro-2a, SI = 5.5; NHDF, SI = 1.9). Ref: S. Aoki, et al, JACS, 2006, 128, 3148│C. FNising, et al, Angew. Chem., Int. Ed., 2008, 47, 9389

H OH

N 17

O

16

HO O

H

N

759 Cortistatin D Type: Buxus. C30H34N2O5 [α]D20 = −37.1° (c = 0.45, MeOH). Source: Sponge Corticium simplex. Pharm: Anti-angiogenic (HUVECs, IC50 = 0.15 μmol/L, SI (= IC50 of testing cells/IC50 of HUVECs) = 1; KB (KB-3-1), IC50 = 55 μmol/L, SI = 460; neuro-2a, IC50 > 300 μmol/L; K562, IC50 > 300 μmol/L; NHDF, IC50 > 300 μmol/L; control Doxorubicin with no selectivity: HUVECs, IC50 = 5.1 nmol/L; KB-3-1, SI = 4.1; K562, SI = 3.5; neuro-2a, SI = 5.5; NHDF, SI = 1.9). Ref: S. Aoki, et al, JACS, 2006, 128, 3148│C. FNising, et al, Angew. Chem., Int. Ed., 2008, 47, 9389

OH

N

17

OH 16

HO O

O

H

N

760 Cortistatin J Type: Buxus. C30H34N2O Powder, [α]D20 = −54° (c = 0.26, CHCl3). Source: Sponge Corticium simplex. Pharm: Cytotoxic (anti-proliferative activity, HUVECs at 8 nmol/L, SI = 300–1000 fold in comparison with other cell lines). Ref: S. Aoki, et al, Tet. Lett., 2007, 48, 4485

10.1 Steroidal Alkaloids

H

287

N 17 16

O

H

N

761 Cephalostatin 1 Type: Cephalostatins. C54H74N2O10 Needles (EtOAc/MeOH), mp 326 °C (dec), [α]D = +102° (c = 0.04, MeOH). Source: Hemichordate tube worm Cephalodiscus gilchristi (off South Africa’s temperate southern coast, yield = 2.3 × 10−7%, two collections of 166 kg and 450 kg in 1981 and 1990). Pharm: Cytotoxic (P388, ED50 = 10–7–10–9 μg/ mL); cytotoxic (NCI’s 60 hmn tumor cell lines panel, mean panel GI50 = 1.2 × 10–9 mol/ L, Compare Correlation Coefficient (Cephalostatin 1 as the “seed”) = 1.00); cytotoxic (NCI screen assay, P388, ED50 = (0.1–0.001 pmol/L)). Ref: G. R. Pettit, et al, JACS, 1988, 110, 2006│G. R. Pettit, et al, JNP, 1994, 57, 52│A. Rudy, et al, JNP,2008, 71, 482│Iglesias-Arteaga, et al, in “The Alkaloids: Chemistry and Biology”, Volume 72, pp. 153–279, H. -J. Knölker, Ed., Academic Press, London, UK, 2013│M. T. DaviesColeman, et al, Mar. Drugs, 2015, 13, 6366 (rev) HO

H N 8'

H H

O

O

OH HO

O

H

O

OH

1

H

H

1' 9'

N H

O

OH

762 Cephalostatin 2 Type: Cephalostatins. C54H74N2O11 Needles (EtOAc/MeOH), mp 350 °C, [α]D = +111° (c = 0.07, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (cell growth inhibitor, powerful). Ref: G. R. Pettit, et al, Chem. Comm., 1988, 865; 1440

288

10 Steroidal and Miscellaneous Alkaloids

HO 26

H N 15'

14'

8'

H

O

H

O

OH

1

OH

H

1'

N

9'

H

H O

O

O

OH HO

OH

763 Cephalostatin 3 Type: Cephalostatins. C55H76N2O11 Needles (EtOAc/MeOH), mp 350 °C, [α]D = +99° (c = 0.15, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Antineoplastic; cell growth inhibitor (powerful). Ref: G. R. Pettit, et al, Chem. Comm., 1988, 865; 1440 HO 26

H N 15'

14'

8'

H H

O

O

OH 9'

OH HO

O

H

O

OH

1

H

1'

N H

O

OH

764 Cephalostatin 4 Type: Cephalostatins. C54H74N2O12 Solid, mp 350 °C, [α]D = +89° (c = 0.11, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (cell growth inhibitor, powerful). Ref: G. R. Pettit, et al, Chem. Comm., 1988, 865-867; 1440

10.1 Steroidal Alkaloids

289

HO

H N OH

O 14'

O

O

O

H

O

OH

H

15'

H

OH HO

N

H

H

O

OH

765 Cephalostatin 5 Type: Cephalostatins. C54H72N2O10 mp 350 °C, [α]D = +100° (c = 0.02, MeOH). Source: Hemichordate Cephalodiscus gilchristi (Indian Ocean, South Africa coast). Pharm: Cytotoxic (P388, cell growth inhibitor, less potent than cephalostatins 1–4) (1989); cytotoxic (NCI’s 60 hmn cancer cell line panel, only two of these hmn cell lines (SNl2kl and CNS U251), GI50 = 10–7–10–8 mol/L) (1992). Ref: G. R. Pettit, et al, Can. J. Chem., 1989, 67, 1509│G. R. Pettit, et al, JOC, 1992, 57, 429

O O

OH H

H N H HO

H

O

OH N H

HO

O

OH

HO

766 Cephalostatin 6 Type: Cephalostatins. C53H70N2O10 mp 350 °C, [α]D = +100° (c = 0.01, MeOH). Source: Hemichordate Cephalodiscus gilchristi (Indian Ocean, South Africa coast). Pharm: Cytotoxic (P388, cell growth inhibitor, less potent than cephalostatins 1–4) (1989); cytotoxic (NCI’s 60 hmn cancer cell line panel, only two of these hmn cell lines (SNl2kl and CNS U251), GI50 = 10–7–10–8 mol/L) (1992). Ref: G. R. Pettit, et al, Can. J. Chem., 1989, 67, 1509│G. R. Pettit, et al, JOC, 1992, 57, 429

290

10 Steroidal and Miscellaneous Alkaloids

O

OH

O H H N H OH HO

N

H

O

H

HO

OH

O HO

767 Cephalostatin 7 Type: Cephalostatins. C54H76N2O11 Amorph. powder, mp 315 °C (dec), [α]D = +106° (c = 0.244, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (HOP-62, DMS273, RXF-393, U251, SF295, CCRF-CEM, HL60, RPMI8226: GI50 = 10–9–10–10 mol/L, remarkable potency); cytotoxic (MCF7; GI50 = 10–8–10–9 mol/L). Ref: G. R. Pettit, et al, JOC, 1992, 57, 429 HO

H N H

O HO

H

O OH

OH HO

O

H

O

OH

H N H

OH

768 Cephalostatin 8 Type: Cephalostatins. C55H78N2O10 Amorph. powder, mp 313 °C (dec), [α]D = +110° (c = 0.1, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (HOP-62, DMS273, RXF-393, U251,SF295, CCRF-CEM, HL60, RPMI8226: GI50 = 10–9–10–10 mol/L, remarkable potency); cytotoxic (breast MCF7 cell line; GI50 = 10–8–10–9 mol/L). Ref: G. R. Pettit, et al, JOC, 1992, 57, 429

10.1 Steroidal Alkaloids

291

HO

H N H

O

H

O

OH

H N

H

O

OH HO

H

O OH

OH

769 Cephalostatin 9 Type: Cephalostatins. C54H76N2O11 Amorph. powder, mp 307 °C (dec), [α]D = +105° (c = 0.5, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (HOP-62, DMS273, RXF-393, U251, SF295, CCRF-CEM, HL60, RPMI8226: GI50 = 10–9–10–10 mol/L, remarkable potency); cytotoxic (breast MCF7 cell line; GI50 = 10–8–10–9 mol/L). Ref: G. R. Pettit, et al, JOC, 1992, 57, 429 OH

H N H H

OH HO

O

H

O

OH

H N H

OH H O

O

OH OH

770 Cephalostatin 10 Type: Cephalostatins. C55H76N2O12 mp > 300 °C, [α]D = +80° (c = 0.17, MeOH). Source: Hemichordate Cephalodiscus gilchristi (Indian Ocean, South Africa coast). Pharm: Cytotoxic (NCI’s 60 hmn tumor cell lines panel, mean panel GI50 = 4.1 × 10–9 mol/L, Compare Correlation Coefficient (Cephalostatin 1 as the “seed”) = 0.88). Ref: G. R. Pettit, et al, JNP, 1994, 57, 52; 1998, 61, 955

292

10 Steroidal and Miscellaneous Alkaloids

26

OH HO O

H 15'

14'

8'

H

9'

OH

H

1'

N

O

H

N 1

OH

HO

O

H

H O

O

O

OH

771 Cephalostatin 11 Type: Cephalostatins. C55H76N2O12 mp > 300 °C, [α]D25 = +75° (c = 0.13, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (NCI’s 60 hmn tumor cell lines panel, mean panel GI50 = 11.0 × 10–9 mol/L, Compare Correlation Coefficient (Cephalostatin 1 as the “seed”) = 0.89). Ref: G. R. Pettit, et al, JNP, 1994, 57, 52 26

OH HO

H

H

N

O HO O

OH

1 15'

14'

8'

H

OH

H

1'

N

9'

H

O

H O

O

O

OH

772 Cephalostatin 12 Type: Cephalostatins. C54H76N2O12 Amorph. solid, mp > 300 °C, [α]D20 = +157.5° (c = 0.4, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (NCI’s 60 hmn tumor cell lines panel, mean panel GI50 = 400 × 10–9 mol/L). Ref: G. R. Pettit, et al, BoMCL, 1994, 4, 1507

10.1 Steroidal Alkaloids

293

HO

H N H HO

O

OH

O

H

O

OH

H N

H

O

OH HO

H

OH

OH

773 Cephalostatin 13 Type: Cephalostatins. C54H76N2O13 Amorph. solid, mp > 300 °C, [α]D20 = +108.1° (c = 0.07, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (NCI’s 60 hmn tumor cell lines panel, mean panel GI50 > 1000 × 10–9 mol/L). Ref: G. R. Pettit, et al, BoMCL, 1994, 4, 1507 HO

H N H HO

O

H

O

OH

H OH

OH

O

N

H

O

OH HO

H

OH

OH

774 Cephalostatin 14 Type: Cephalostatins. C54H72N2O12 Amorph. powder, [α]D = +80.9° (c = 0.11, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (cell growth inhibitor). Ref: G. R. Pettit, et al, Can. J. Chem., 1994, 72, 2260│G. R. Pettit, et al, JOC, 1995, 60, 608

294

10 Steroidal and Miscellaneous Alkaloids

HO 26

H N O

H

O

OH

1 8'

14'

OH

H

1'

15'

N

9'

H

H O

O

O

OH HO

O

OH

775 Cephalostatin 15 Type: Cephalostatins. C55H74N2O12 Amorph. powder, mp > 300 °C, [α]D = +71.5° (c = 0.34, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Antineoplastic. Ref: G. R. Pettit, et al, Can. J. Chem., 1994, 72, 2260 HO 26

H N

OH HO

O

H

O

OH

1

O

8'

14'

OH

H

O

O

H

1'

15' 9'

N H

O

OH

776 Cephalostatin 16 Type: Cephalostatins. C54H74N2O10 Amorph. solid, mp > 300 °C, [α]D = +55° (c = 1.72, MeOH). Source: Hemichordate Cephalodiscus gilchristi (South Africa). Pharm: Cytotoxic. Ref: G. R. Pettit, et al, BoMCL, 1994, 4, 1507; 1995, 5, 2027

10.1 Steroidal Alkaloids

295

OH OH HO

O

H

H

O

N H

OH N

H

H H HO

O

O

O

777 Cephalostatin 17 Type: Cephalostatins. C54H74N2O10 Amorph. powder, [α]D = +70° (c = 0.7, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (cell growth inhibitor). Ref: G. R. Pettit, et al, BoMCL, 1995, 5, 2027 26

H N OH H H

O

O

OH HO

O

H

O

OH

1

H

1'

N H

O

OH

778 Cephalostatin 18 Type: Cephalostatins. C55H76N2O11 Amorph. solid, mp > 300 °C, [α]D25 = +95° (c = 0.06, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (P388, ED50 = 4.3 × 10–3 μg/mL); cytotoxic (mini panel of hmn cancer cell lines (OVCAR-3, SF295, A498, NCI-H460, KM20L2, and SK-MEL-5), GI50 < 10–3 μg/mL); cytotoxic (NCI’s 60 hmn cancer cell line panel, mean panel GI50 = (21.7 ± 9.9) × 10–9 mol/L, Compare Correlation Coefficient (Cephalostatin 1 as the “seed”) = 0.94). Ref: G. R. Pettit, et al, JNP, 1998, 61, 955

296

10 Steroidal and Miscellaneous Alkaloids

HO

OH HO

O

H

O

O

H N

OH

1 9'

H

1'

N

H

H

H

O

O

O

OH

779 Cephalostatin 19 Type: Cephalostatins. C55H76N2O11 Amorph. solid, mp > 300 °C, [α]D25 = +67° (c = 0.05, MeOH). Source: Hemichordate Cephalodiscus gilchristi. Pharm: Cytotoxic (P388, ED50 = 7.4 × 10–3 μg/mL); cytotoxic (mini panel of hmn cancer cell lines (OVCAR-3, SF295, A498, NCI-H460, KM20L2, and SK-MEL-5), GI50 < 10–3 μg/mL); cytotoxic (NCI’s 60 hmn cancer cell line panel, mean panel GI50 = (16.6 ± 9.5) × 10–9 mol/L, Compare Correlation Coefficient (Cephalostatin 1 as the “seed”) = 0.92). Ref: G. R. Pettit, et al, JNP, 1998, 61, 955 HO

H N

OH HO

O

H

O

OH

1 9'

N

H H

O

O O

H

1'

H

O

OH

780 4-Acetoxyplakinamine B Type: Plakinamines. C33H52N2O2 Glass, [α]D = +21.9° (c = 0.001, MeOH). Source: Sponge Corticium sp. Pharm: Nervous system activity (acetylcholinesterase inhibitor, IC50 = 3.75 μmol/L, MMOA: mixed-competitive inhibition). Ref: R. Langjae, et al, Steroids, 2007, 72, 682

10.1 Steroidal Alkaloids

297

N

H

H N H

O

H

H

O

781 24,25-Dihydroplakinamine A Type: Plakinamines. C29H48N2 [α]D = +7.4° (c = 0.015, CHCl3). Source: Sponge Corticium sp. (Vanuatu). Pharm: Cytotoxic (NSCLC-N6, in vitro, IC50 = 5.7 μg/mL). Ref: S. De Marino, et al, EurJOC, 1999, 697

H N

H 2N

782 Dihydroplakinamine K Type: Plakinamines. C32H54N2O2 Oil (dihydrochloride), [α]D = +5.7° (c = 0.05, MeOH) (dihydrochloride). Source: Sponge Corticium niger. Pharm: Cytotoxic (HCT116, IC50 = 1.4 μmol/L). Ref: C. P. Ridley, et al, JNP, 2003, 66, 1536 25

30 24

H

4

N H

O O

NH

23

298

10 Steroidal and Miscellaneous Alkaloids

783 Lokysterolamine A Type: Plakinamines. C31H50N2O Oil, [α]D25 = +17.7° (c = 0.1, MeOH). Source: Sponge Corticium sp. (Sulawesi, Indonesia). Pharm: Cytotoxic (in vitro, P388, IC50 = 0.5 μg/ mL; A549, IC50 = 0.5 μg/mL; HT29, IC50 = 1 μg/mL; MEL28, IC50 = 5 μg/mL); antibacterial (Bacillus subtilis, 50μg/disc, IZD = 19 mm); antifungal (Candida albicans, 50μg/disc, IZD = 11 mm); medium immunomodulatory activity (LCV > 25.0, MLR = 0.13, LCV/MLR > 187). Ref: J. Jurek, et al, JNP, 1994, 57, 1004 25

24

23

N

N OH

784 Lokysterolamine B Type: Plakinamines. C31H48N2O2 Semicryst. Solid, [α]D26 = −3.1° (c = 1.6, CHCl3). Source: Sponge Corticium sp. (Sulawesi, Indonesia). Pharm: Cytotoxic (in vitro, P388, IC50 = 1 μg/mL; A549, IC50 = 0.5 μg/mL; HT29, IC50 = 1 μg/mL; MEL28, IC50 > 2 μg/mL); antibacterial (Bacillus subtilis, 50μg/disc, IZD = 8 mm); medium immunomodulatory activity (LCV > 12.5, MLR = 0.48, LCV/MLR > 26). Ref: J. Jurek, et al, JNP, 1994, 57, 1004

N O N H

OH

785 N3-Methyl-4-oxo-3-epi-plakinamine B Type: Plakinamines. C32H50N2O [α]D = +35.4° (c = 0.01, CHCl3/MeOH). Source: Sponge Corticium sp. (Vanuatu). Pharm: Cytotoxic (NSCLC-N6, in vitro, IC50 = 3.6 μg/mL). Ref: S. De Marino, et al, EurJOC, 1999, 697

10.1 Steroidal Alkaloids

299

N

H

N O

786 N30-Methyl-23ξ,24ξ,25,30-tetrahydroplakinamine A Type: Plakinamines. C30H52N2 [α]D = +23.0° (c = 0.02, CHCl3). Source: Sponge Corticium sp. (Vanuatu). Pharm: Cytotoxic (NSCLC-N6, in vitro, IC50 = 4.9 μg/mL). Ref: S. De Marino, et al, EurJOC, 1999, 697

N

H 2N

787 Plakinamine A Type: Plakinamines. C29H46N2 mp 120–130 °C (dec), [α]D = +16° (c = 1.02, CHCl3). Source: Sponge Plakina sp. Pharm: Antibacterial (Staphylococcus aureus and Candida albicans). Ref: R. M. Rosser, et al, JOC, 1984, 49, 5157

25

30 24

N 23

H

4

H 2N

788 Plakinamine B Type: Plakinamines. C31H50N2 Mp 180–200 °C (dec), [α]D = +29° (c = 1.19, MeOH). Source: Sponge Plakina sp. Pharm: Antibacterial (Staphylococcus aureus); antifungal (Candida albicans). Ref: R. M. Rosser, et al, JOC, 1984, 49, 5157

300

10 Steroidal and Miscellaneous Alkaloids

N

H N H

H

H

789 Plakinamine C Type: Plakinamines. C33H54N2O2 [α]D = +29.4° (c = 0.016, CHCl3). Source: Sponge Corticium sp. (Vanuatu). Pharm: Cytotoxic (NSCLC-N6, in vitro, IC50 = 0.1 μg/mL). Ref: S. De Marino, et al, EurJOC, 1999, 697

N OH H

N O

790 Plakinamine D Type: Plakinamines. C33H54N2O2 [α]D = +25.2° (c = 0.013, CHCl3). Source: Sponge Corticium sp. (Vanuatu). Pharm: Cytotoxic (NSCLC-N6, in vitro, IC50 < 3.3 μg/mL). Ref: S. De Marino, et al, EurJOC, 1999, 697

N

OH

H

N O

791 Plakinamine E Type: Plakinamines. C31H50N2O2 Gum, [α]D25 = +9.3° (c = 0.2, MeOH). Source: Sponge Corticium sp. (Guam). Pharm: Cytotoxic (moderate); antifungal; nucleic acid-cleaving properties. Ref: H. S. Lee, et al, JNP, 2001, 64, 1474

10.1 Steroidal Alkaloids

N

301

+

–

O N OH

792 Plakinamine F Type: Plakinamines. C31H48N2O Gum, [α]D25 = +8.4° (c = 0.1, MeOH). Source: Sponge Corticium sp. (Guam). Pharm: Cytotoxic (moderate); antifungal; nucleic acidcleaving activity. Ref: H. S. Lee, et al, JNP, 2001, 64, 1474

N

N O

793 Plakinamine I Type: Plakinamines. C31H50N2 Oil (dihydrochloride), [α]D = +45.2° (c = 0.32, MeOH) (dihydrochloride). Source: Sponge Corticium niger. Pharm: Cytotoxic (HCT116, IC50 = 10.6 μmol/L); selective cytotoxic (Bristol-Myers Squib Pharmaceutical Research Institute 11 cancer cell line panel, mean IC50 = 5.6 μmol/L, max IC50/min IC50 = 25, having greatest selectivity). Ref: C. P. Ridley, et al, JNP, 2003, 66, 1536

H

H N H H

H

N H

794 Plakinamine J Type: Plakinamines. C30H50N2 Oil (dihydrochloride), [α]D = +25° (c = 0.1, MeOH) (dihydrochloride). Source: Sponge Corticium niger. Pharm: Cytotoxic (HCT116, IC50 = 6.1 μmol/L); selective cytotoxic (Bristol-Myers Squib Pharmaceutical Research Institute 11 cancer cell line panel, mean IC50 = 6.0 μmol/L, max IC50/min IC50 = 13, having selectivity). Ref: C. P. Ridley, et al, JNP, 2003, 66, 1536

302

10 Steroidal and Miscellaneous Alkaloids

H

N H H NH2

795 Plakinamine K Type: Plakinamines. C32H52N2O2 Oil, [α]D = +38.4° (c = 0.25, MeOH). Source: Sponge Corticium niger. Pharm: Cytotoxic (HCT116, IC50 = 1.4 μmol/L); selective cytotoxic (Bristol-Myers Squib Pharmaceutical Research Institute 11 cancer cell line panel, mean IC50 = 1.6 μmol/L, max IC50/min IC50 = 5, most potent). Ref: C. P. Ridley, et al, JNP, 2003, 66, 1536

H

HN H N H

H O O

796 Plakinamine M Type: Plakinamines. C33H58N2O Source: Sponge Corticium sp. (New Britain I., Papua New Guinea). Pharm: Antituberculosis. Ref: Z. Lu, et al, JNP, 2013, 76, 2150

N

H HO H N

H

H

10.2 Miscellaneous Alkaloids

303

10.2 Miscellaneous Alkaloids 797 Benzoxacystol Type: Morpholines. C17H18N2O6S Source: Marine-derived streptomycete Streptomyces griseus (deep sea sediment, Canary Basin). Pharm: Glycogen synthase kinase 3β inhibitor; antiproliferative (mouse broblast cells, weak). Ref: J. Nachtigall, et al, J. Antibiot., 2011, 64, 453 O

H N O

O

N H S

O

O

O

798 Chelonin A 2-(3-Indolyl)-6-(3,4,5-trimethoxyphenyl)morpholine Type: Morpholines. C21H24N2O4 Cryst. (MeOH), mp 182 °C, [α]D = −11.7° (c = 0.32, CHCl3). Source: Sponge Chelonaplysilla sp. (Palau, Oceania). Pharm: Antibacterial (Bacillus subtilis, in vivo); anti-inflammatory. Ref: S. C. Bobzin, et al, JOC, 1991, 56, 4403│M. Somei, et al, Heterocycles, 1995, 41, 5 H N O

O N H

O O

799 2-Amino-8-benzoyl-6-hydroxy-3H-phenoxazin-3-one Type: Phenoxazine alkaloids (other than actinomycins). C19H12N2O4 Red solid. Source: Marine bacterium Halomonas sp. GWS-BW-H8hM. Pharm: Antibacterial (50 μg on 6 mm filter discs: Escherichia coli, IZD = 0 mm, control Actinomycin D, IZD = 16 mm; Bacillus subtilis,IZD = 16 mm, Actinomycin D, IZD = 35 mm; Staphylococcus aureus, IZD = 10 mm, Actinomycin D, IZD = 25 mm); antifungal (50 μg on 6 mm filter discs: Candida albicans, IZD = 0 mm, Actinomycin D, IZD = 0 mm); cytotoxic (HM02, GI50 = 1.4 μg/mL, TGI = 2.6 μg/mL, control Actinomycin D, GI50 = 0.002 μg/mL, TGI = 0.008 μg/mL; HepG2, GI50 = 3.2 μg/mL, TGI = 10 μg/mL, Actinomycin D, GI50 = 0.0015 μg/mL, TGI = 0.0065 μg/mL; MCF7, GI50 = 2.0 μg/mL, TGI = 3.2 μg/mL, Actinomycin D, GI50 = 0.0024 μg/mL, TGI = 0.011 μg/mL). Ref: J. Bitzer, et al, J. Antibiot., 2006, 59, 86

304

10 Steroidal and Miscellaneous Alkaloids

O N

NH2

O

O

OH

800 2-Amino-6-hydroxy-3H-phenoxazin-3-one Type: Phenoxazine alkaloids (other than actinomycins). C12H8N2O3 Red solid. Source: Marine bacterium Halomonas sp. GWS-BW-H8hM. Pharm: Antibacterial (50 μg on 6 mm filter discs: Escherichia coli, IZD = 0 mm; Bacillus subtilis, IZD = 25 mm, control Actinomycin D, IZD = 35 mm; Staphylococcus aureus, IZD = 16 mm, Actinomycin D, IZD = 25 mm); antifungal (50 μg on 6 mm filter discs: Candida albicans, IZD = 0 mm); cytotoxic (HM02, GI50 = 1.6 μg/mL, TGI = 2.6 μg/mL, control Actinomycin D, GI50 = 0.002 μg/mL, TGI = 0.008 μg/mL; HepG2, GI50 = 4.3 μg/mL, TGI > 10 μg/mL, Actinomycin D, GI50 = 0.0015 μg/mL, TGI = 0.0065 μg/mL; MCF7, GI50 = 1.6 μg/mL, TGI = 2.7 μg/mL, Actinomycin D, GI50 = 0.0024 μg/mL, TGI = 0.011 μg/mL). Ref: J. Bitzer, et al, J. Antibiot., 2006, 59, 86 N 7

2

O

NH2

O

OH

801 2-Amino-3H-phenoxazin-3-one Questiomycin A Type: Phenoxazine alkaloids (other than actinomycins). C12H8N2O2 Dark brown or red cryst. (EtOH), mp 250–251 °C. Source: Marine bacterium Halomonas sp. GWS-BW-H8hM. Pharm: Antibacterial (50 μg on 6 mm filter discs: Escherichia coli, IZD = 0 mm, control Actinomycin D, IZD = 16 mm; Bacillus subtilis,IZD = 20 mm, Actinomycin D, IZD = 35 mm; Staphylococcus aureus, IZD = 15 mm, Actinomycin D, IZD = 25 mm); antifungal (50 μg on 6 mm filter discs: Candida albicans, IZD = 25 mm, Actinomycin D, IZD = 0 mm); cytotoxic (HM02, GI50 = 0.95 μg/mL, TGI = 2.2 μg/mL, control Actinomycin D, GI50 = 0.002 μg/mL, TGI = 0.008 μg/mL; HepG2, GI50 = 1.4 μg/ mL, TGI = 5.6 μg/mL, Actinomycin D, GI50 = 0.0015 μg/mL, TGI = 0.0065 μg/mL; MCF7, GI50 = 0.13 μg/mL, TGI = 0.42 μg/mL, Actinomycin D, GI50 = 0.0024 μg/mL, TGI = 0.011 μg/mL); cell cycle inhibitor; aromatase and sulfatase inhibitor. Ref: J. Bitzer, et al, J. Antibiot., 2006, 59, 86 N 7

O

2

NH2

O

10.2 Miscellaneous Alkaloids

305

802 Carboxyexfoliazone Type: Phenoxazine alkaloids (other than actinomycins). C15H10N2O5 Source: Marinederived streptomycete Streptomyces venezuelae (sediment, Guam), terrestrial streptomycete Streptomyces sp. Pharm: Cytotoxic (panel of HTCLs: HCT8, BGC823, A549, A2780, Bel7402, NIH-H460, all IC50 > 30 μmol/L, weak). Ref: A. Zeeck, et al, Eur. Pat. Appl., EP 260486 A1 19880323, 1998│J. Ren, et al, Bioorg. Med. Chem. Lett., 2013, 23, 301 O N

H N

O

O

HO O

803 Chandrananimycin C Type: Phenoxazine alkaloids (other than actinomycins). C17H16N2O3 Orange solid. Source: Marine-derived actinomycete Actinomadura sp. M045, marine-derived bacterium Halomonas sp. GWS-BW-H8hM. Pharm: Antibiotic. Ref: R. P. Maskey, et al, J. Antibiot., 2003, 56, 622│J. Bitzer, et al, J. Antibiot., 2006, 59, 86 O N

NH

O

O

804 Chandrananimycin D Type: Phenoxazine alkaloids (other than actinomycins). C15H12N2O5 Orange solid. Source: Marine-derived streptomycete Streptomyces venezuelae (sediment, Guam), terrestrial streptomycete Streptomyces sp. (old building). Pharm: Cytotoxic (panel of HTCLs: HCT8, BGC823, A549, A2780, Bel7402, NIH-H460, all IC50 > 30 μmol/L, weak) (Ren, 2013); cytotoxic (antiproliferative: K562, GI50 = 16.6 μmol/L; HUVEC, GI50 = 5.3 μmol/L; THP-1, GI50 = 27.6 μmol/L; Raji, GI50 = 9.6 μmol/L; HEK-293, GI50 = 10.3 μmol/L; HepG2, GI50 = 6.6 μmol/L; MCF7, GI50 = 1.3 μmol/L) (Gomes, 2010); cytotoxic (HeLa, CC50 = 90.6 μmol/L) (Gomes, 2010). Ref: P. B. Gomes, et al, JNP, 2010, 73, 1461│J. Ren, et al, Bioorg. Med. Chem. Lett., 2013, 23, 301

N

H N

OH

HO O

O

O

306

10 Steroidal and Miscellaneous Alkaloids

805 Exfoliazone 2-Acetamido-8-(hydroxymethyl)-3H-phenoxazin-3-one Type: Phenoxazine alkaloids (other than actinomycins). C15H12N2O4 Orange needles (CHCl3), mp 294–296 °C. Source: Marine-derived streptomycete Streptomyces venezuelae (sediment, Guam), terrestrial streptomycete Streptomyces sp. Pharm: Cytotoxic (panel of HTCLs: HCT8, IC50 = 4.89 μmol/L, control 5-FU, IC50 = 5.38 μmol/L, BGC823, IC50 = 3.40 μmol/L, 5-FU, IC50 = 3.84 μmol/L, A549, IC50 = 9.16 μmol/L, 5-FU, IC50 = 1.54 μmol/L, A2780, IC50 = 2.52 μmol/L, 5-FU, IC50 = 5.40 μmol/L, Bel7402, IC50 > 10 μmol/L, 5-FU, IC50 = 3.85 μmol/L, NIH-H460, IC50 = 13.6 μmol/L, 5-FU, IC50 = 7.12 μmol/L); antifungal (Valsa ceratosperma). Ref: S. Imai, et al, J. Antibiot., 1990, 43, 1606│J. Ren, et al, Bioorg. Med. Chem. Lett., 2013, 23, 301 HO

N O O N H

O

806 Venezueline A Type: Phenoxazine alkaloids (other than actinomycins). C24H21N3O6 Source: Marinederived streptomycete Streptomyces venezuelae (sediment, Guam). Pharm: Cytotoxic (panel of HTCLs: HCT8, BGC823, A549, A2780, Bel7402, NIH-H460, all IC50 > 30 μmol/L, weak). Ref: J. Ren, et al, Bioorg. Med. Chem. Lett., 2013, 23, 301 O

OH O

HO

N

NH

N H

O

O

807 Venezueline E Type: Phenoxazine alkaloids (other than actinomycins). C18H16N2O5 Source: Marinederived streptomycete Streptomyces venezuelae (sediment, Guam) Pharm: Cytotoxic (panel of HTCLs: HCT8, BGC823, A549, A2780, Bel7402, NIH-H460, all IC50 > 30 μmol/ L, weak). Ref: J. Ren, et al, Bioorg. Med. Chem. Lett., 2013, 23, 301

10.2 Miscellaneous Alkaloids

307

O O O

N

NH

O

O

808 Phloeodictine A Type: Phloeodictines. C26H49N5O Colorless amorph. solid. Source: Sponge Phloeodictyon sp. (New Caledonia). Pharm: Antibacterial (gram-positive and -negative bacteria, in vitro); cytotoxic (KB, moderate). Ref: E. Kourany-Lefoll, et al, JOC, 1992, 57, 3832 HO 10

N

H N

N

NH2 NH

809 Phloeodictine A1 Type: Phloeodictines. C25H47N5O Amorphous solid (as dichloride). Source: Sponge Phloeodictyon sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 2.2 μg/mL). Ref: E. Kourany-Lefoll, et al, Tetrahedron, 1994, 50, 3415

NH

HO N

N

N H

NH2

810 Phloeodictine A2 Type: Phloeodictines. C24H45N5O Amorphous solid (as dichloride). Source: Sponge Phloeodictyon sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 2.2 μg/mL). Ref: E. Kourany-Lefoll, et al, Tetrahedron, 1994, 50, 3415

HO N

N

H N

NH2 NH

811 Phloeodictine A3 Type: Phloeodictines. C23H43N5O Amorphous solid (as dichloride). Source: Sponge Phloeodictyon sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 3.5 μg/mL). Ref: E. Kourany-Lefoll, et al, Tetrahedron, 1994, 50, 3415

308

10 Steroidal and Miscellaneous Alkaloids

NH

HO N

N

N H

NH2

812 Phloeodictine A4 Type: Phloeodictines. C22H41N5O Source: Sponge Phloeodictyon sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 3.5 μg/mL). Ref: E. Kourany-Lefoll, et al, Tetrahedron, 1994, 50, 3415 HO N

N

H N

NH2 NH

813 Phloeodictine A5 Type: Phloeodictines. C22H41N5O Source: Sponge Phloeodictyon sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 3.5 μg/mL). Ref: E. Kourany-Lefoll, et al, Tetrahedron, 1994, 50, 3415 NH

HO N

N

N H

NH2

814 Phloeodictine A6 Type: Phloeodictines. C26H51N5O Amorphous solid (as dichloride). Source: Sponge Phloeodictyon sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 0.6 μg/mL). Ref: E. Kourany-Lefoll, et al, Tetrahedron, 1994, 50, 3415

NH

HO N

N

N H

NH2

815 Phloeodictine A7 Type: Phloeodictines. C25H49N5O Source: Sponge Phloeodictyon sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 0.6 μg/mL). Ref: E. Kourany-Lefoll, et al, Tetrahedron, 1994, 50, 3415

10.2 Miscellaneous Alkaloids

HO N

H N

N

309

NH2 NH

816 Phloeodictyne B Type: Phloeodictines. C27H53N8OS+3 Colorless amorph. solid. Source: Sponge Phloeodictyon sp. (New Caledonia). Pharm: Antibacterial (gram-positive and -negative bacteria, in vitro); cytotoxic (KB, moderate). Ref: E. Kourany-Lefoll, et al, JOC, 1992, 57, 3832 H N H 2N

S N

+

H

H 7

HO N

N

+

H N

H

NH2 N

+

H

817 Amaminol A Type: Miscellaneous acyclic alkaloids. C18H31NO Pale yellow oil, [α]D24 = −170.8° (c = 0.2, MeOH). Source: An unidentified ascidian (family Polyclinidae, Ukeshima Is. Japan). Pharm: Cytotoxic (P388, IC50 = 2.1 μg/mL). Ref: N. U. Sata, et al, Tet. Lett., 2000, 41, 489 NH2 HO 2

H

H

818 Amaminol B Type: Miscellaneous acyclic alkaloids. C18H31NO Pale yellow oil, [α]D24 = −112.4° (c = 0.2, MeOH). Source: An unidentified ascidian (family Polyclinidae, Ukeshima Is. Japan). Pharm: Cytotoxic (P388, IC50 = 2.1 μg/mL). Ref: N. U. Sata, et al, Tet. Lett., 2000, 41, 489

310

10 Steroidal and Miscellaneous Alkaloids

NH2 HO 2

H

H

819 Cyclodidemniserinol Type: Miscellaneous acyclic alkaloids. C38H66N2O19S3 Oil (tri-Na salt), [α]D = −26.6° (tri-Na salt). Source: Ascidian Didemnum guttatum (Palau, Oceania). Pharm: HIV-1 integrase inhibitor. Ref: S. S. Mitchell, et al, Org. Lett., 2000, 2, 1605 H O H N

O S O

O H N

O

H

S

O

O O

O O

O

O

O

O

O

O H

O

S

O

O

820 GB4 Toxin 2-(1-Methyl-2-oxopropylidene)phosphorohydrazidothioate oxime Type: Miscellaneous acyclic alkaloids. C10H22N3O3PS Needles (C6H6), mp 82–83 °C. Source: Dinoflagellate Ptychodiscus brevis [Syn. Gymnodinium breve]. Pharm: Toxin. Ref: M. Alam, et al, JACS, 1982, 104, 5232 S O

P O

H N N N OH

821 Lobatamide A Type: Miscellaneous acyclic alkaloids. C27H32N2O8 [α]D = −7.9° (c = 0.24, MeOH). Source: Ascidians Aplidium lobatum (Australia) and Aplidium sp. (deep water, Philippines). Pharm: Cytotoxic (NCI hmn tumor 60 cell-line screen. negative log GI50 values (mol/L), [leukemia] CCRF-CEM (9.21), HL60 (TB) (9.59), K562 (8.72),

10.2 Miscellaneous Alkaloids

311

Molt4 (9.05), RPMI8226 (8.89), SR (9.59); [nonsmall cell lung] A549/ATCC (9.00), EKVX (8.92), HOP-62 (9.49), HOP-92 (8.85), NCI-H226 (9.48), NCI-H23 (8.36), NCIH322M (8.31), NCI-H460 (9.15), NCI-H522 (8.70); [colon] Colon205 (9.12), HCT116 (9.11), HCT15 (8.60), HT29 (9.35), KM12 (9.04), SW620 (8.77); [CNS] SF268 (9.32), SF295 (9.44), SF539 (9.13), SNB19 (> 7.00), SNB75 (8.34), U251 (9.00); [melanoma] LOX-IMVI (9.70), MALME-3M (8.52), M14 (9.57), SK-MEL-2 (8.89), SK-MEL-28 (8.12), SK-MEL-5 (9.60), UACC-257 (9.11), UACC62 (9.32); [ovarian] IGROV1 (8.60), OVCAR-3 (8.96), OVCAR-5 (7.51), OVCAR-8 (9.22), SK-OV-3 (> 7.00); [renal] 786-0 (9.39), A498 (7.42), ACHN (9.10), CAKI-1 (8.70), RXF-393 (9.68), SN12C (7.49), TK10 (7.59), UO-31 (8.82); [prostate] PC3 (8.29), DU145 (8.27); [breast] MCF7 (8.14), MCF7/ADR-RES (8.60), MDA-MB-231/ATCC (7.77), Hs578T (8.57), MDA-MB-435 (9.03), MDA-N (8.80), BT-549 (9.30), T47D (8.70)). Ref: D. L. Galinis, et al, JOC, 1997, 62, 8968│T. C. McKee, et al, JOC, 1998, 63, 7805 O

N 26

H N

OH

O

O O

24Z

O

O 30

HO

822 Lobatamide B Lobatamide A 26Z-isomer Type: Miscellaneous acyclic alkaloids. C27H32N2O8 [α]D = −15.0° (c = 0.03, MeOH). Source: Ascidians Aplidium lobatum (Australia) and Aplidium sp. (deep water, Philippines). Pharm: Cytotoxic. Ref: D. L. Galinis, et al, JOC, 1997, 62, 8968│T. C. McKee, et al, JOC, 1998, 63, 7805

N 26Z

H N

OH

O

O O

HO

O

O

O

312

10 Steroidal and Miscellaneous Alkaloids

823 Lobatamide C Lobatamide A 24E-isomer Type: Miscellaneous acyclic alkaloids. C27H32N2O8 [α]D = −15.5° (c = 0.113, MeOH). Source: Ascidians Aplidium lobatum (Australia) and Aplidium sp. (deep water, Philippines). Pharm: Cytotoxic. Ref: T. C. McKee, et al, JOC, 1998, 63, 7805 N H N

OH

O

O O

O

24E

O

O

HO

824 Lobatamide D 30-Hydroxy-lobatamide A Type: Miscellaneous acyclic alkaloids. C27H32N2O9 [α]D = −35.0° (c = 0.08, MeOH). Source: Ascidians Aplidium lobatum (Australia) and Aplidium sp. (deep water, Philippines). Pharm: Cytotoxic. Ref: D. L. Galinis, et al, JOC, 1997, 62, 8968│T. C. McKee, et al, JOC, 1998, 63, 7805 O

N

H N

OH

O

O O

O

O OH

HO

825 Poecillanosine Type: Miscellaneous acyclic alkaloids. C19H38N2O4 Solid, [α]D25 = −20.2° (c = 0.1, MeOH). Source: Sponge Poecillastra aff. tenuilminaris. Pharm: Antioxidant (free radical scavenger); cytotoxic. Ref: T. Natori, et al, Tet. Lett., 1997, 38, 8349

N O

O

OH

N O

10.2 Miscellaneous Alkaloids

313

826 O,O,O′,O′-Tetrapropyl 2,2′-(1,2-dimethyl-1,2-ethanediylidene)bis (phosphorohydrazidothioate) Type: Miscellaneous acyclic alkaloids. C16H36N4O4P2S2 Cryst. (EtOH), mp 124–125 °C. Source: Marine-derived fungus Lignincola laevis (from marsh grass). Pharm: Cytotoxic (L1210, 0.25 μg/mL). Ref: S. P. Abraham, et al, Pure Appl. Chem., 1994, 66, 2391 O S

N

P

N

N O H

H O N P

S

O

827 1,5-Diazacycloheneicosane Type: Miscellaneous monocyclic alkaloids. C19H40N2 Pale yellow solid. Source: Sponge Mycale sp. (Lamu I., Kenya). Pharm: Cytotoxic (A549, GI50 = 5.41 μmol/L, control Doxorubicin, GI50 = 0.32 μmol/L; HT29, GI50 = 5.07 μmol/L, Doxorubicin, GI50 = 0.36 μmol/L; MDA-MB-231, GI50 = 5.74 μmol/L, Doxorubicin, GI50 = 0.26 μmol/L). Ref: L. Coello, et al, Mar. Drugs, 2009, 7, 445

4

HN

NH

828 Discoipyrrole C Type: Miscellaneous monocyclic alkaloids. C20H21NO4 Source: Marine-derived bacterium Bacillus hunanensis (sediment, Galveston Bay, Texas, USA). Pharm: Tyrosine kinase inhibitor (inhibit signaling pathway). Ref: Y. Hu, et al, JACS, 2013, 135, 13387 HO

NH

HO

OH O

829 (4E,S)-Dysidazirine Type: Miscellaneous monocyclic alkaloids. C19H33NO2 Oil, [α]D = +47.2° (c = 108, CHCl3). Source: Sponge Dysidea fragilis (Pohnpei I., Federated States of Micronesia).

314

10 Steroidal and Miscellaneous Alkaloids

Pharm: Cytotoxic (L1210, 0.27 μg/mL); antibacterial (gram-negative bacterium Pseudomonas aeruginosa, 4 μg/disk); antifungal (yeast Candida albicans and Saccharomyces cerevisiae, 4 μg/disk). Ref: T. F. Molinski, et al, JOC, 1988, 53, 2103 N

O O

H

830 (4E,R)-(–)-Dysidazirine Type: Miscellaneous monocyclic alkaloids. C19H33NO2 Low melting solid, [α]D20 = −186.3° (MeOH). Source: Sponge Dysidea fragilis. Pharm: Cytotoxic (L1210, 0.27 μg/mL); antibacterial (gram-negative bacterium Pseudomonas aeruginosa, 4 μg/disk); antifungal (yeast Candida albicans and Saccharomyces cerevisiae, 4 μg/disk). Ref: T. F. Molinski, et al, JOC, 1988, 53, 2103│F. A. Davis, et al, JACS, 1995, 117, 3651 N H O

O

831 Haliclorensin Type: Miscellaneous monocyclic alkaloids. C13H28N2 Oil, [α]D = +20° (c = 2, MeOH). Source: Sponge Haliclona tulearensis (South Africa). Pharm: Cytotoxic (P388, IC50 = 0.1 mg/mL). Ref: G. Koren-Goldshlager, et al, JNP, 1998, 61, 282│M. R. Heinrich, et al, Tetrahedron, 2001, 57, 9973

NH NH

832 Halimedin Type: Miscellaneous monocyclic alkaloids. C10H16N6O Cryst., mp 164–165 °C. Source: Green alga Halimeda xishaensis (Xisha Is., South China Sea). Pharm: Antibacterial (Escherichia coli and Staphylococcus aureus). Ref: J. Y. Su, et al, Phytochemistry, 1998, 48, 583

10.2 Miscellaneous Alkaloids

315

O N

N N

N H

N H

CN

833 Keramaphidin C (Z)-Azacyclo-6-undecene Type: Miscellaneous monocyclic alkaloids. C10H19N Amorph. solid, mp 106–109 °C. Source: Sponge Amphimedon sp. (Kerama I., Okinawa). Pharm: Biogenetic precursor of manzamine alkaloids. Ref: M. Tsuda, et al, Tet. Lett., 1994, 35, 4387 H N

834 Neamphine Type: Miscellaneous bicyclic alkaloids. C6H5N3OS Needles (hexane/CHCl3). Source: Sponge Neamphius huxleyi. Pharm: Cytotoxic. Ref: E. D. de Silva, et al, Tet. Lett., 1991, 32, 2707 S N

N N

O

835 Zarzissine Type: Miscellaneous bicyclic alkaloids. C5H5N5 Crystals (H2O or MeOH), mp > 300 °C (dec). Source: Sponge Anvhinoe paupertas (Mediterranean Sea). Pharm: Cytotoxic; antifungal (Candida sp.). Ref: N. Bouaicha, et al, JNP, 1994, 57, 1455 N

N

N

N H

NH2

836 Aaptosine Type: Miscellaneous tricyclic alkaloids. C13H12N2O2 Yellow oil. Source: Sponge Aaptos aaptos (Okinawa). Pharm: Cytotoxic. Ref: A. Rudi, et al, Tet. Lett., 1993, 34, 4683

316

10 Steroidal and Miscellaneous Alkaloids

H N

O

N

O

837 Ammosamide A Type: Miscellaneous tricyclic alkaloids. C12H10ClN5OS Blue solid. Source: Marinederived streptomycete Streptomyces sp. NPS-698 (sediment, Bahamas). Pharm: Cell cycle modulator. Ref: C. C. Hughes, et al, Angew. Chem., Int. Ed., 2009, 48, 725; 728 NH2 Cl

N S

2

NH2 N

NH2

O

838 Aplidiopsamine A Type: Miscellaneous tricyclic alkaloids. C17H13N7 Yellow gum. Source: Ascidian Aplidiopsis confluata (Bathurst Harbour, W. Tasmania, Australia). Pharm: Antimalarial (CSPF 3D7, IC50 = 1.47 μmol/L; CRPF Dd2, IC50 = 1.65 μmol/L; novel lead); cytotoxic (HEK-293, 120 μmol/L). Ref: A. R. Carroll, et al, JOC, 2010, 75, 8291

HN

N N N

N N

NH2

839 Aurantiomide B Type: Miscellaneous tricyclic alkaloids. C18H22N4O4 Amorph. powder, [α]D24 = +96.5° (c = 0.09, CHCl3). Source: Marine-derived fungus Penicillium aurantiogriseum SP0-16 from sponge Mycale plumose (China waters). Pharm: Cytotoxic (several cell lines, moderate). Ref: Z. H. Xin, et al, JNP, 2007, 70, 853

10.2 Miscellaneous Alkaloids

317

12

HO HN

N

1

N

O

O

O

NH2

840 Aurantiomide C Type: Miscellaneous tricyclic alkaloids. C18H20N4O3 Amorph. powder, [α]D24 = +25.8° (c = 0.1, CHCl3). Source: Marine-derived fungus Penicillium aurantiogriseum SP0-16 from sponge Mycale plumose (China waters). Pharm: Cytotoxic (several cell lines, moderate). Ref: Z. H. Xin, et al, JNP, 2007, 70, 853

H 12

Z

HN

N 1

N O O

O

NH2

841 Baculiferin I Type: Miscellaneous tricyclic alkaloids. C32H23NO12S Amorphous orange-yellow solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Binding capacity to HIV-1 targets (20 μg/ mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 638.4; recombinant protein hmn APOBEC3G (innate intracellular anti-viral factor), RU = not detected; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 1351.0). Ref: G. Fan, et al, BoMC, 2010, 18, 5466

318

10 Steroidal and Miscellaneous Alkaloids

HO

OH

OH

O S

O

O

OH O

O

N

HO HO

OH

842 Baculiferin J Type: Miscellaneous tricyclic alkaloids. C32H23NO12S Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Binding capacity to HIV-1 targets (20 μg/mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 528.0; recombinant protein hmn APOBEC3G (innate intracellular anti-viral factor), RU = 765.4; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 1485.4). Ref: G. Fan, et al, BoMC, 2010, 18, 5466

HO

OH

OH OH

O

O

N

HO HO

O

O S

OH O

843 Baculiferin K Type: Miscellaneous tricyclic alkaloids. C32H23NO9 Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 = 5.5 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4-LTR-β-gal indicator cells), IC50 < 0.4 μg/mL); binding capacity to HIV-1

10.2 Miscellaneous Alkaloids

319

targets (20 μg/mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 448.4; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 523.3). Ref: G. Fan, et al, BoMC, 2010, 18, 5466

HO

OH

OH

OH

O

O

N

HO HO

OH

844 Baculiferin N Type: Miscellaneous tricyclic alkaloids. C26H17NO10 Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 = 4.4 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4-LTR-β-gal indicator cells), IC50 < 0.1 μg/mL); binding capacity to HIV-1 targets (20 μg/mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 596.8; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 952.9). Ref: G. Fan, et al, BoMC, 2010, 18, 5466

HO

OH

OH

OH

O

O

N

OH HO

O HO

845 Brevianamide M Type: Miscellaneous tricyclic alkaloids. C18H15N3O3 Cubic cryst., mp 206–207 °C, [α]D20 = −147.7° (c = 0.13, Me2CO). Source: Marine-derived fungi Aspergillus

320

10 Steroidal and Miscellaneous Alkaloids

versicolor from brown alga Sargassum thunbergii (Pingtan I., Fujian, China) and Aspergillus versicolor. Pharm: Antibacterial (30 μg/disk: Escherichia coli, IZD = 11 mm, control Chloramphenicol, IZD = 32 mm; Staphylococcus aureus, IZD = 10 mm, Chloramphenicol, IZD = 31 mm); toxic (brine shrimp Artemia salina, 30 μg/disk, Lethal Rate = 47.6%). Ref: G. -Y. Li, et al, Org. Lett., 2009, 11, 3714│F. -P. Miao, et al, Mar. Drugs, 2012, 10, 131

O O

N NH N OH

846 Callophycin A Type: Miscellaneous tricyclic alkaloids. C19H18N2O3 Brown oil, [α]D22 = −2.0° (c = 0.1, MeOH). Source: Red alga Callophycus oppositifolius (Pugh Shoal, Northern Territory, Australia). Pharm: Cytotoxic (SF268, GI50 = 1.3 μmol/L; MCF7, GI50 = 4.2 μmol/L; H460, GI50 = 2.0 μmol/L; HT29, GI50 = 1.7 μmol/L; CHO-K1, GI50 = 0.59 μmol/L). Ref: S. P. B. Ovenden, et al, Phytochem. Lett., 2011, 4, 69 O

OH

N HO N H

847 Chaetominedione Type: Miscellaneous tricyclic alkaloids. C17H12N2O4 Amorph. yellow powder (Me2CO). Source: Marine-derived fungus Chaetomium sp. Pharm: Tyrosine kinase p56lck inhibitor (IC50 (estimated) ≤ 200 μg/mL). Ref: A. Abdel-Lateff, Tet. Lett., 2008, 49, 6398 O NH O

N H O

OH

10.2 Miscellaneous Alkaloids

321

848 Cylindrospermopsin Type: Miscellaneous tricyclic alkaloids. C15H21N5O7S Off-white microcryst., [α]D = −31° (c = 0.1, H2O). Source: Cyanobacterium Cylindrospermopsis raciborskii (Palm I., Queensland). Pharm: Hepatotoxin; glutathione synthesis inhibitor. Ref: I. Ohtani, et al, JACS, 1992, 114, 7941 OH

–

O

H

H

O

O

S O

O

N

NH

H N

HN

+

NH O

H The posotive charge spreaded in region of NCNN.

849 Deoxynyboquinone Type: Miscellaneous tricyclic alkaloids. C15H12N2O4 Red triclinic crystal. Source: Marine-derived bacterium Pseudonocardia sp. SCSIO 01299 (depth of 3258 m, deep sea sediment, South China Sea, E 120°0.975′, N 19°0.664′). Pharm: Cytotoxic (SF268, IC50 = 0.022 μmol/L, control Cisplatin, IC50 = 3.99 μmol/L; MCF7, IC50 = 0.015 μmol/L, Cisplatin, IC50 = 9.24 μmol/L; NCI-H460, IC50 = 0.080 μmol/L, Cisplatin, IC50 = 1.53 μmol/L); antibacterial (Bacillus thuringiensis SCSIO BT01, MIC = 1 μg/mL; Staphylococcus aureus ATCC 29213, MIC = 1 μg/mL; Enterococcus faecalis, ATCC 29212, MIC = 1 μg/mL). Ref: S. Li, et al, Mar. Drugs, 2011, 9, 1428 O

O

N H

N

O

O

850 Discoipyrrole A Type: Miscellaneous tricyclic alkaloids. C27H23NO5 Source: Marine-derived bacterium Bacillus hunanensis (sediment, Galveston Bay, Texas, USA). Pharm: Tyrosine kinase inhibitor (inhibit signaling pathway). Ref: Y. Hu, et al, JACS, 2013, 135, 13387

322

10 Steroidal and Miscellaneous Alkaloids

HO

N

HO

O

O

O

851 Discoipyrrole B Type: Miscellaneous tricyclic alkaloids. C27H23NO4 Source: Marine-derived bacterium Bacillus hunanensis (sediment, Galveston Bay, Texas, USA). Pharm: Tyrosine kinase inhibitor (inhibit signaling pathway). Ref: Y. Hu, et al, JACS, 2013, 135, 13387 HO

N O

O

O

852 Discoipyrrole D Type: Miscellaneous tricyclic alkaloids. C38H34N2O7 Source: Marine-derived bacterium Bacillus hunanensis (sediment, Galveston Bay, Texas, USA). Pharm: Tyrosine kinase inhibitor (inhibit signaling pathway). Ref: Y. Hu, et al, JACS, 2013, 135, 13387 OH

HO

OH

N H

N

HO

O

O

O

853 Divergolide B Type: Miscellaneous tricyclic alkaloids. C31H37NO7 Source: Mangrove-derived streptomycete Streptomyces sp. from mangrove Bruguiera gymnorrhiza (stem). Pharm: Cytotoxic; antibacterial (Bacillus subtilis and Mycobacterium vaccae). Ref: L. Ding, et al, Angew. Chem., Int. Ed., 2011, 50, 1630

10.2 Miscellaneous Alkaloids

323

OH

O O

HN O

O O

HO

854 Gymnodimine Type: Miscellaneous tricyclic alkaloids. C32H45NO4 Amorph. solid, [α]D25 = −246° (c = 1.76, CHCl3); [α]D25 = −10.4° (EtOH). Source: Dinoflagellate Gymnodinium sp. (New Zealand). Pharm: Neurotoxin (to rise to neurotoxin shellfish poisoning in New Zealand oysters); positive to ninhydrin and Dragendorff reagents; LD (mus ip) = 0.45 mg/kg. Ref: T. Seki, et al, Tet. Lett., 1995, 36, 7093 H

O H O

OH

H

H

O

N

855 Gymnodimine B Type: Miscellaneous tricyclic alkaloids. C32H45NO5 Source: Dinoflagellate Gymnodinium selliforme (New Zealand). Pharm: Neurotoxin (shellfish, implicated in occurrences of neurotoxic poisoning). Ref: C. O. Miles, et al, J. Agric. Food Chem., 2000, 48, 1373 H HO O H

H

O O

H

18

OH N

324

10 Steroidal and Miscellaneous Alkaloids

856 Haouamine A Type: Miscellaneous tricyclic alkaloids. C32H27NO4 Solid, [α]D29 = −52° (c = 0.4, MeOH). Source: Ascidian Aplidium haouarianum. Pharm: Cytotoxic (HT29, IC50 = 0.1 μg/mL, selective activity). Ref: L. Garrido, et al, JOC, 2003, 68, 293 OH

OH

OH

OH

N H

857 Haouamine B Type: Miscellaneous tricyclic alkaloids. C32H27NO5 Solid (penta-Ac), [α]D26 = −27.1° (c = 0.14, CHCl3) (penta-Ac). Source: Ascidian Aplidium haouarianum. Pharm: Cytotoxic (MS-1, IC50 = 5 μg/mL, slight activity). Ref: L. Garrido, et al, JOC, 2003, 68, 293│M.Matveenko, et al, JACS, 2012, 134, 9291 OH

OH

OH

21

HO

N

OH

H

858 N3′-Methyltetrahydrovariolin B Type: Miscellaneous tricyclic alkaloids. C15H17N7O Light yellow solid, mp 226 °C (dec), [α]D = −22.4° (c = 3.5, MeOH). Source: Sponge Kirkpatrickia variolosa (Antarctic). Pharm: Antifungal (inhibits growth of Saccharomyces cerevisiae, 2 mg/mL, IZD = 36 mm); cytotoxic (in vitro, HCT116, IC50 = 0.48 μg/mL); antineoplastic (in vivo, P388, 10 mg/kg, T/C = 125%, only modest). Ref: N. B. Perry, et al, Tetrahedron, 1994, 50, 3987│G. Trimurtulu, et al, Tetrahedron, 1994, 50, 3993

10.2 Miscellaneous Alkaloids

N

325

NH2 N OH

N

N N NH2

859 Monanchomycalin A Type: Miscellaneous tricyclic alkaloids. C47H85N6O51+ Source: Sponge Monanchora pulchra (Sea of Okhotsk, Russia). Pharm: Cytotoxin (low nmol/L level). Ref: T. N. Makarieva, et al, Tet. Lett., 2012, 53, 4228

H2N O H N

H O N N

O

+

O

N

15

H

NH2

O

860 Monanchomycalin B Type: Miscellaneous tricyclic alkaloids. C45H81N6O51+ Source: Sponge Monanchora pulchra (Sea of Okhotsk, Russia). Pharm: Cytotoxin (low nmol/L level). Ref: T. N. Makarieva, et al, Tet. Lett., 2012, 53, 4228

H2N O

H O N

H N N

O

+

O 15

H

N

NH2

O

861 Nakijinamine A Type: Miscellaneous tricyclic alkaloids. C24H25BrN4O22+ Source: Sponge Suberites sp. (Unten Port, Okinawa). Pharm: Antifungal (Candida albicans, Cryptococcus

326

10 Steroidal and Miscellaneous Alkaloids

neoformans and Trichophyton mentagrophytes); antibacterial (Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus). Ref: Y. Takahashi, et al, Tetrahedron, 2012, 68, 8545

N

+

OH

Br

HO H N

N H

+

N H

862 Nakijinamine B Type: Miscellaneous tricyclic alkaloids. C24H26N4O22+ Source: Sponge Suberites sp. (Unten Port, Okinawa). Pharm: Antifungal (Candida albicans). Ref: Y. Takahashi, et al, Tetrahedron, 2012, 68, 8545

N

+

OH HO H N

N H

+

N H

863 Nakijinamine F Type: Miscellaneous tricyclic alkaloids. C29H34BrN5O22+ Source: Sponge Suberites sp. (Unten Port, Okinawa). Pharm: Antifungal (Candida albicans). Ref: Y. Takahashi, et al, Tetrahedron, 2012, 68, 8545

O

N

OH

+

Br

HN H

N

N H

+

N H

10.2 Miscellaneous Alkaloids

327

864 Ningalin B Type: Miscellaneous tricyclic alkaloids. C25H19NO8 Dark yellow solid, mp 303 °C, [α]D = 0° (c = 0.5, MeOH). Source: Ascidian Didemnum sp. (Western Australia). Pharm: Multidrug resistance reversing agents (a new class, potent). Ref: H. Kang, et al, JOC, 1997, 62, 3254│D. L. Boger, et al, JOC, 2000, 65, 2479 HO

OH

OH

HO

O HO

N O

HO

865 Ningalin C Type: Miscellaneous tricyclic alkaloids. C32H23NO10 Amorphous red solid, [α]D = 0° (c = 0.2, MeOH). Source: Ascidian Didemnum sp. (Western Australia). Pharm: Kinases inhibitors CK1δ, CDK5 and GSK3β (potent). Ref: H. Kang, et al, JOC, 1997, 62, 3254│C. Peschko, et al, Tet. Lett., 2000, 41, 9477│F. Plisson, et al, Chem Med Chem, 2012, 7, 983 HO

OH

OH OH OH

O

O N

OH

HO HO

866 Oxepinamide A Type: Miscellaneous tricyclic alkaloids. C17H21N3O5 Yellow oil, [α]D = +43° (c = 0.001, CHCl3). Source: Marine-derived fungus Acremonium sp. (widespread) from ascidian Ecteinascidia turbinata (Bahamas). Pharm: Anti-inflammatory (topical 0.1 μg/ear RTX-induced mouse ear edema assay, dose 50 μg/ear, InRt = 82%, strong). Ref: G. N. Belofsky, et al, Chem. Eur. J., 2000, 6, 1355

328

10 Steroidal and Miscellaneous Alkaloids

O

O

O N 11

N

O

NH

HO

867 Penipanoid B Type: Miscellaneous tricyclic alkaloids. C16H13N3O2 White powder, [α]D25 = +30° (c = 0.1, MeOH). Source: Marine-derived fungus Penicillium paneum (sediment, South China Sea). Pharm: Antibacterial (Staphylococcus aureus and Escherichia coli); antifungal (Alternaria brassicae, Fusarium oxysporium, Fusarium vasinfectum, Coniella diplodiella, Physalospora piricola and Aspergillus niger). Ref: C. -S. Li, et al, JNP, 2011, 74, 1331 O NH H

OH

N N

868 Pterocellin A Type: Miscellaneous tricyclic alkaloids. C16H16N2O3 Dark red needles (toluene), mp 172–173 °C. Source: Bryozoan Pterocella vesiculosa. Pharm: Cytotoxic (P388, IC50 = 477 ng/mL); antibacterial (gram-positive bacterium Bacillus subtilis, MID ≤ 0.3 μg/ disk); antifungal (Trichophyton mentagrophytes, MID = 3.9–7.5 μg/disk). Ref: B. Yao, et al, JNP, 2003, 66, 1074 H

O

O 6

N

N

O

869 Pterocellin B Type: Miscellaneous tricyclic alkaloids. C19H14N2O3 Amorph. red solid. Source: Bryozoan Pterocella vesiculosa. Pharm: Cytotoxic (P388, IC50 = 323 ng/mL); antibacterial (gram-positive bacterium Bacillus subtilis, MID ≤ 0.3 μg/disk); antifungal (Trichophyton mentagrophytes, MID = 3.9–7.5 μg/disk). Ref: B. Yao, et al, JNP, 2003, 66, 1074

10.2 Miscellaneous Alkaloids

H

329

O

O 6

N

N

O

870 Salinosporamide C Type: Miscellaneous tricyclic alkaloids. C14H18ClNO3 Oil, [α]D = −33.6° (c = 0.27, MeOH). Source: Marine-derived actinomycete Salinispora tropica CNB-392. Pharm: Cytotoxic. Ref: P. G. Williams, et al, JOC, 2005, 70, 6196 H

OH H

O

N H Cl O

871 Schulzeine A Type: Miscellaneous tricyclic alkaloids. C42H72N2O16S3 Powder (tri-Na salt), [α]D22 = +40° (c = 0.1, MeOH) (tri-Na salt). Source: Sponge Penares schulzei. Pharm: α-Glucosidase inhibitor. Ref: K. Takada, et al, JACS, 2004, 126, 187│E. G. Bowen, et al, JACS, 2009, 131, 6062

O 20R

OH

O

S O

6

HO

O H

HO N

S

O O

O

O

OH N H

9

O

S O

O OH

872 Schulzeine B Type: Miscellaneous tricyclic alkaloids. C41H67N2O16S3 Powder (tri-Na salt), [α]D22 = −23° (c = 0.1, MeOH) (tri-Na salt). Source: Sponge Penares schulzei. Pharm: α-Glucosidase inhibitor (potent). Ref: K. Takada, et al, JACS, 2004, 126, 187│E. G. Bowen, et al, JACS, 2009, 131, 6062

330

10 Steroidal and Miscellaneous Alkaloids

OH O

S

O

O

OH O

HO N OH

H

O

11b

O O

S

S

O

O

O O

OH

N H

873 Schulzeine C Type: Miscellaneous tricyclic alkaloids. C41H67N2O16S3 Powder (tri-Na salt), [α]D22 = +33° (c = 0.1, MeOH) (tri-Na salt). Source: Sponge Penares schulzei. Pharm: α-Glucosidase inhibitor (potent). Ref: K. Takada, et al, JACS, 2004, 126, 187│E. G. Bowen, et al, JACS, 2009, 131, 6062 OH O

S

O

O

OH O

HO N OH

H

O

11b

O O

S

S

O

O

O O

OH

N H

874 Scytonemin Type: Miscellaneous tricyclic alkaloids. C36H20N2O4 Yellow green crystals, mp 325 °C. Source: Cyanobacteria Scytonema sp. (Curacao, Netherlands Antilles, Caribbean Sea), Lyngbya sp. (Huahine, Polynesia (Fr.)) and Stigonema sp. (Waldo Lake, Oregon). Pharm: Pigment (ultraviolet sunscreen). Ref: P. J. Proteau, et al, Experientia, 1993, 49, 825

OH

O N N HO

O

10.2 Miscellaneous Alkaloids

331

875 Symbioimine Type: Miscellaneous tricyclic alkaloids. C19H23NO5S Cryst. + 1H2O (H2O), mp 214–215 °C (dec), [α]D27 = +245° (c = 0.1, DMSO). Source: Dinoflagellates Symbiodinium sp. and Amphiscolops sp. Pharm: Cyclooxygenase-2 inhibitor, osteoclast differentiation inhibitor. Ref: M. Kita, et al, JACS, 2004, 126, 4794│M. Kita, et al, BoMC, 2005, 13, 5253 OH O O

H H

S

–

O O

H N

+

H

876 Terreusinone Type: Miscellaneous tricyclic alkaloids. C18H22N2O4 Yellowish solid, mp 230 °C (dec), [α]D = +47° (c = 0.3, MeOH). Source: Marine-derived fungus Aspergillus terreus MFA460 (culture). Pharm: UV-A absorbing activity (ED50 = 70 μg/mL). Ref: S. M. Lee, et al, Tet. Lett., 2003, 44, 7707│M. Saleem, et al, NPR, 2007, 24, 1142 (rev) O H N

HO

N H

OH

O

877 2,3,5,7-Tetrabromo-1H-benzofuro[3,2-b]pyrrole Type: Miscellaneous tricyclic alkaloids. C10H3Br4NO Amorph. solid. Source: Marinederived bacterium Pseudoalteromonas sp. CMMED 290. Pharm: Antibacterial (MRSA). Ref: D. Fehér, et al, JNP, 2010, 73, 1963 H N

Br

Br Br O Br

332

10 Steroidal and Miscellaneous Alkaloids

878 5,6,9,10-Tetracarboxybenzo[b][1,8]naphthyridinium(1+) Type: Miscellaneous tricyclic alkaloids. C16H9N2O81+ Amorph. solid. Source: Mussel (green mussel) Perna viridis (hemolymph). Pharm: Serine protease inhibitor. Ref: M. S. Khan, et al, BoMCL, 2008, 18, 3963 HO

O COOH

N HO

O

+

N

COOH

879 Usabamycin A Type: Miscellaneous tricyclic alkaloids. C16H20N2O2 Source: Marine-derived streptomycete Streptomyces sp. (sediment, Usa Bay, Kochi Prefecture, Japan). Pharm: Cytotoxic (HeLa, IC50 = 106.6 μmol/L); selective serotonin uptake inhibitor (serotonin receptor 5-HT2B, IC50 = 12.4 μmol/L, KI = 7.89 μmol/L). Ref: S. Sato, et al, BoMCL, 2011, 21, 7099 O

H N

H

N O

880 Usabamycin B Type: Miscellaneous tricyclic alkaloids. C15H18N2O2 [α]D = +206.8° (c = 0.20, CHCl3). Source: Marine-derived streptomycete Streptomyces sp. (sediment, Usa Bay, Kochi Prefecture, Japan). Pharm: Cytotoxic (HeLa, IC50 = 103.5 μmol/L); selective serotonin uptake inhibitor (serotonin receptor 5-HT2B, IC50 = 8.45 μmol/L, KI = 5.38 μmol/ L). Ref: S. Sato, et al, BoMCL, 2011, 21, 7099 O

H N

H

N O

10.2 Miscellaneous Alkaloids

333

881 Usabamycin C Type: Miscellaneous tricyclic alkaloids. C15H18N2O [α]D = +251.3° (c = 0.20, CHCl3). Source: Marine-derived streptomycete Streptomyces sp. (sediment, Usa Bay, Kochi Prefecture, Japan). Pharm: Cytotoxic (HeLa cell, IC50 = 101.9 μmol/L); selective serotonin uptake inhibitor (5-HT2B, IC50 = 8.24 μmol/L, KI = 5.24 μmol/L). Ref: S. Sato, et al, BoMCL, 2011, 21, 7099 H N

H

N O

882 Variolin A Type: Miscellaneous tricyclic alkaloids. C15H13N7O2 Red solid, mp 196 °C (dec). Source: Sponge (bright red sponge) Kirkpatrickia variolosa (psychrophilic, cold water, Antarctic benthos). Pharm: Cytotoxic (P388, IC50 = 3.8 μg/mL, mechanism of action is inhibition of cyclin-dependent kinase (CDK)). Ref: N. B. Perry, et al, Tetrahedron, 1994, 50, 3987│G. Trimurtulu, et al, Tetrahedron, 1994, 50, 3993│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)

N

+

NH2 N

O

N

OH

N

N

NH2

883 Variolin B Type: Miscellaneous tricyclic alkaloids. C14H11N7O Yellow prisms (TFA aq), mp 45 °C (dec). Source: Sponge (bright red sponge) Kirkpatrickia variolosa (psychrophilic, cold water, Antarctic benthos). Pharm: Cytotoxic (P388, IC50 = 0.21 μg/mL); cytotoxic (P388, mechanism of action is inhibition of cyclin-dependent kinase CDK); CDK inhibitor (IC50 = 0.03 μmol/L, selective inhibiting towards CDK1 and CDK2 over CDK4 and CDK7). Ref: N. B. Perry, et al, Tetrahedron, 1994, 50, 3987│G. Trimurtulu, et al, Tetrahedron, 1994, 50, 3993│R. J. Anderson, et al, Tet. Lett., 2001, 42, 8697│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)│D. Skropeta, et al, Mar. Drugs, 2011, 9, 2131 (rev)

334

10 Steroidal and Miscellaneous Alkaloids

N

NH2

1' 5'

3'

N OH

N

N N NH2

884 Xylopyridine A Type: Miscellaneous tricyclic alkaloids. C24H14N2O2 ellow needles (EtOAc/petrol), mp 200–202 °C, [α]D25 = +35°. Source: Mangrove-derived fungus Xylaria sp. 2508 (Mai Po, Hong Kong, China). Pharm: DNA-binding affinity (calf thymus DNA, strong). Ref: F. Xu, et al, Chin. J. Chem., 2009, 27, 365 O N

N

O

885 Zyzzyanone A Type: Miscellaneous tricyclic alkaloids. C20H19N3O3 Purple solid (trifluoroacetate salt), mp 300 °C (dec) (TFA salt). Source: Sponge Zyzzya fuliginosa (Australia). Pharm: Cytotoxic (EAC, IC50 = 25 μg/mL); inhibits cell division (fertilized sea urchin eggs, 25 μg/mL); UV-protective activity. Ref: N. K. Utkina, et al, Tet. Lett., 2004, 45, 7491│N. K. Utkina, et al, JNP, 2005, 68, 1424│A. E. Makarchenko, et al, Chem Nat Compd., 2006, 42, 78 HO H N O 2'

N

N H

1

O

886 Zyzzyanone B Type: Miscellaneous tricyclic alkaloids. C19H17N3O3 Purple solid (TFA salt). Source: Sponge Zyzzya fuliginosa (Australia). Pharm: Cytotoxic (mouse Ehrlich carcinoma cells, moderate); UV-protective activity. Ref: N. K. Utkina, et al, Tet. Lett., 2004, 45,

10.2 Miscellaneous Alkaloids

335

7491│N. K. Utkina, et al, JNP, 2005, 68, 1424│A. E. Makarchenko, et al, Chem Nat Compd., 2006, 42, 78 HO H N O 2'

N H

N H

1

O

887 Zyzzyanone C Type: Miscellaneous tricyclic alkaloids. C21H19N3O4 Brownish-red solid (TFA salt). Source: Sponge Zyzzya fuliginosa (Australia). Pharm: Cytotoxic (mouse Ehrlich carcinoma cells, moderate); UV-protective activity. Ref: N. K. Utkina, et al, Tet. Lett., 2004, 45, 7491│N. K. Utkina, et al, JNP, 2005, 68, 1424│A. E. Makarchenko, et al, Chem Nat Compd., 2006, 42, 78 HO O N O 2'

N

N H

1

O

888 Zyzzyanone D Type: Miscellaneous tricyclic alkaloids. C20H17N3O4 Brownish-red solid (TFA salt). Source: Sponge Zyzzya fuliginosa (Australia). Pharm: Cytotoxic (mouse Ehrlich carcinoma cells, moderate); UV-protective activity. Ref: N. K. Utkina, et al, Tet. Lett., 2004, 45, 7491│N. K. Utkina, et al, JNP, 2005, 68, 1424│A. E. Makarchenko, et al, Chem Nat Compd., 2006, 42, 78 HO

O N O 2'

N H

N H

O

1

336

10 Steroidal and Miscellaneous Alkaloids

889 Aspeverin Type: Miscellaneous tetra-and higher-cyclic alkaloids. C22H24N4O2 Source: Marinederived fungus Aspergillus versicolor dl-29 from green alga Codium fragile (Dalian, China). Pharm: Growth inhibitor (phytoplankton microalga Heterosigma akashiwo, moderate); toxic (brine shrimp Artemia salina); antibacterial (Vibrio ichthyoenteri, Proteus mirabilis, Enterobacter cloacae and Bacillus cereus). Ref: N. -Y. Ji, et al, Org. Lett., 2013, 15, 2327 O CN O

NH N

N H

H

890 Asporyzin A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C28H37NO3 Source: Marinederived fungus Aspergillus oryzae (endophytic) from red alga Heterosiphonia japonica (Yantai, China). Pharm: AChE modulator (low). Ref: M. -F. Qiao, et al, BoMCL, 2010, 20, 5677 H O

N H

H

O

O

891 Asporyzin B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C28H37NO3 Source: Marinederived fungus Aspergillus oryzae (endophytic) from red alga Heterosiphonia japonica (Yantai, China). Pharm: AChE modulator (low). Ref: M. -F. Qiao, et al, BoMCL, 2010, 20, 5677 OH

H

N H O

O

892 Asporyzin C Type: Miscellaneous tetra-and higher-cyclic alkaloids. C28H39NO2 Source: Marinederived fungus Aspergillus oryzae (endophytic) from red alga Heterosiphonia

10.2 Miscellaneous Alkaloids

337

japonica (Yantai, China). Pharm: Antibacterial (Escherichia coli, strong); AChE modulator (low). Ref: M. -F. Qiao, et al, BoMCL, 2010, 20, 5677 H

H

N H

OH OH

893 Auranthine Type: Miscellaneous tetra-and higher-cyclic alkaloids. C19H14N4O2 Amorph. solid, [α]D25 = −164° (c = 1, EtOH). Source: Marine-derived fungus Penicillium aurantiogriseum (mud, Bohai Sea, China), fungus Penicillium aurantiogriseum. Pharm: Mycotoxin; nephrotoxic. Ref: F. Song, et al, Mar. Drugs, 2012, 10, 1297│S. E. Yeulet, et al, JCS Perkin I, 1986, 1891

N

O N H

O N N

894 Baculiferin A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C40H27NO14S Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Multidrug reversal activity (antifungal of Brefeldin A in presence of 30 μmol/L alkaloid Baculiferin A, Candida albicans sensitive GU4 strain, MIC = 12.5 μg/mL, negative control 1% DMSO, MIC = 6.3 μg/ mL; Candida albicans resistant GU5 strain, MIC = 50 μg/mL, negative control 1% DMSO, MIC = 50 μg/mL); anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 = 7.6 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4-LTR -β-gal indicator cells), IC50 = 3.7 μg/mL); binding capacity to HIV-1 targets (20 μg/ mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 110.7; recombinant protein hmn APOBEC3G (innate intracellular anti-viral factor), RU = 170.6; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 17.1). Ref: G. Fan, et al, BoMC, 2010, 18, 5466

338

10 Steroidal and Miscellaneous Alkaloids

O HO

S HO

O

O

HO

OH

O

O N

OH

HO OH

HO

OH

895 Baculiferin B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C40H27NO14S Amorphous darkred solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Multidrug reversal activity (antifungal of Brefeldin A in presence of 30 μmol/L alkaloid Baculiferin B, Candida albicans sensitive GU4 strain, MIC = 12.5 μg/mL, negative control 1% DMSO, MIC = 6.3 μg/mL; Candida albicans resistant GU5 strain, MIC = 50 μg/mL, negative control 1% DMSO, MIC = 50 μg/mL); anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 = 2.2 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4-LTR-β-gal indicator cells), IC50 = 1.3 μg/mL); binding capacity to HIV-1 targets (20 μg/mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 152.4; recombinant protein hmn APOBEC3G (innate intracellular anti-viral factor), RU = 89.7; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 12.9). Ref: G. Fan, et al, BoMC, 2010, 18, 5466

HO

HO

OH

O

O N

O HO

OH

S O

OH

O OH

HO

OH

10.2 Miscellaneous Alkaloids

339

896 Baculiferin C Type: Miscellaneous tetra-and higher-cyclic alkaloids. C40H27NO17S2 Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 = 8.4 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4-LTR-β-gal indicator cells), IC50 = 1.2 μg/ mL); binding capacity to HIV-1 targets (20 μg/mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 296.4; recombinant protein hmn APOBEC3G (innate intracellular anti-viral factor), RU = 885.9; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 115.8). Ref: G. Fan, et al, BoMC, 2010, 18, 5466

HO

HO

OH

OH

O

O N

HO O O S O

O S OH O

O

OH

HO

OH

897 Baculiferin D Type: Miscellaneous tetra-and higher-cyclic alkaloids. C40H27NO17S2 Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Multidrug reversal activity (antifungal of Brefeldin A in presence of 30 μmol/L alkaloid Baculiferin D, Candida albicans sensitive GU4 strain, MIC = 12.5 μg/mL, negative control 1% DMSO, MIC = 6.3 μg/mL; Candida albicans resistant GU5 strain, MIC = 50 μg/mL, negative control 1% DMSO, MIC = 50 μg/mL). Ref: G. Fan, et al, BoMC, 2010, 18, 5466

340

10 Steroidal and Miscellaneous Alkaloids

O S OH

O HO S

O O

O HO O

OH

O

O N

OH

HO OH

HO

OH

898 Baculiferin E Type: Miscellaneous tetra-and higher-cyclic alkaloids. C40H27NO17S2 Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Multidrug reversal activity (antifungal of Brefeldin A in presence of 30 μmol/L alkaloid Baculiferin E, Candida albicans sensitive GU4 strain, MIC = 12.5 μg/mL, negative control 1% DMSO, MIC = 6.3 μg/ mL; Candida albicans resistant GU5 strain, MIC = 50 μg/mL, negative control 1% DMSO, MIC = 50 μg/mL); anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 = 4.6 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4LTR-β-gal indicator cells), IC50 = 2.7 μg/mL); binding capacity to HIV-1 targets (20 μg/mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 361.9; recombinant protein hmn APOBEC3G (innate intracellular anti-viral factor), RU = 991.5; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 108.7). Ref: G. Fan, et al, BoMC, 2010, 18, 5466 O HO

S

HO O

HO

O

O

O N

O HO

OH

S O O

OH OH

HO

OH

10.2 Miscellaneous Alkaloids

341

899 Baculiferin F Type: Miscellaneous tetra-and higher-cyclic alkaloids. C40H27NO17S2 Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Multidrug reversal activity (antifungal of Brefeldin A in presence of 30 μmol/L alkaloid Baculiferin F, Candida albicans sensitive GU4 strain, MIC = 12.5 μg/mL, negative control 1% DMSO, MIC = 6.3 μg/ mL; Candida albicans resistant GU5 strain, MIC = 50 μg/mL, negative control 1% DMSO, MIC = 50 μg/mL); anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 = 4.6 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4LTR-β-gal indicator cells), IC50 = 2.7 μg/mL); binding capacity to HIV-1 targets (20 μg/mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 361.9; recombinant protein hmn APOBEC3G (innate intracellular anti-viral factor), RU = 991.5; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 108.7). Ref: G. Fan, et al, BoMC, 2010, 18, 5466 O HO

S

HO O

HO

O

OH

O

O N

O S

OH

O O

HO OH

HO

OH

900 Baculiferin G Type: Miscellaneous tetra-and higher-cyclic alkaloids. C40H27NO20S3 Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 = 3.2 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4-LTR-β-gal indicator cells), IC50 = 4.4 μg/mL); binding capacity to HIV-1 targets (20 μg/mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 446.8; recombinant protein hmn APOBEC3G (innate intracellular anti-viral factor), RU = 571.8; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 125.1); cytotoxic (HCT8, Bel7402, BGC823, A549 and A2780, IC50 = 19.7 μmol/L, moderate). Ref: G. Fan, et al, BoMC, 2010, 18, 5466

342

10 Steroidal and Miscellaneous Alkaloids

O HO

S

HO O

HO

O

OH

O

O N

O HO

O S OH

S O O

O O OH

HO

OH

901 Baculiferin H Type: Miscellaneous tetra-and higher-cyclic alkaloids. C40H27NO20S3 Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 = 1.4 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4-LTR-β-gal indicator cells), IC50 = 1.3 μg/mL); binding capacity to HIV-1 targets (20 μg/mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/ mm2) = 259; recombinant protein hmn APOBEC3G (innate intracellular anti-viral factor), RU = 578.5; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 76.2). Ref: G. Fan, et al, BoMC, 2010, 18, 5466 O

O HO

S OH

S

HO O

OO

O

O

O N

O HO

OH

S O O

OH OH

HO

OH

10.2 Miscellaneous Alkaloids

343

902 Baculiferin L Type: Miscellaneous tetra-and higher-cyclic alkaloids. C32H21NO12 Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 = 7.0 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4-LTR-β-gal indicator cells), IC50 = 4.1 μg/mL); binding capacity to HIV-1 targets (20 μg/mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 1983.2; recombinant protein hmn APOBEC3G (innate intracellular anti-viral factor), RU = 2170.7; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 469.0). Ref: G. Fan, et al, BoMC, 2010, 18, 5466

HO

OH

OH OH O

O N

OH

O

HO HO HO

OH

903 Baculiferin M Type: Miscellaneous tetra-and higher-cyclic alkaloids. C32H21NO15S Amorphous dark-red solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Multidrug reversal activity (antifungal of Brefeldin A in presence of 30 μmol/L alkaloid Baculiferin M, Candida albicans sensitive GU4 strain, MIC = 12.5 μg/mL, negative control 1% DMSO, MIC = 6.3 μg/ mL; Candida albicans resistant GU5 strain, MIC = 50 μg/mL, negative control 1% DMSO, MIC = 50 μg/mL); anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 = 5.0 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4LTR-β-gal indicator cells), IC50 = 0.2 μg/mL); binding capacity to HIV-1 targets (20 μg/mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 1897.0; recombinant protein hmn APOBEC3G (innate intracellular anti-viral factor), RU = 2463.5; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = 379.7); cytotoxic (HCT8, Bel7402, BGC823, A549 and A2780, IC50 = 65.8 μmol/ L, moderate). Ref: G. Fan, et al, BoMC, 2010, 18, 5466

344

10 Steroidal and Miscellaneous Alkaloids

O

HO O

S O

OH

HO

OH O

O N

OH

O

HO HO

OH

HO

904 Baculiferin O Type: Miscellaneous tetra-and higher-cyclic alkaloids. C18H9NO11S Amorphous light-yellow solid. Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005). Pharm: Cytotoxic (HCT8, Bel7402, BGC823, A549 and A2780, IC50 = 33.1 μmol/L, moderate). Ref: G. Fan, et al, BoMC, 2010, 18, 5466 O HO O HO

S HO

O

O

O O

OH

N H

O

905 Calothrixin A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C19H10N2O3 Long wine red needles (DMSO). Source: Cyanobacterium Calothrix sp. (soil). Pharm: AnticancerCell-Effect (model: hmn CEM cells, mechanism: cell cycle inhibition) (Khan, 2009); cytotoxic (3H-thymidine incorporation assay, HeLa) (Chen, 2003); cytotoxic (MTT assay, CEM, IC50 = 0.20–5.13 μmol/L); poison of DNA topoisomerase I; antiplasmodial (CRPF, IC50 = 58 nmol/L). Ref: R. W. Rickards, et al, Tetrahedron, 1999, 55, 13513│X. X. Chen, et al, J. Appl. Phycol. 2003, 15, 269│Q. A. Khan, et al, JNP 2009, 72, 438

10.2 Miscellaneous Alkaloids

345

O N

O

N H O

906 Calothrixin B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C19H10N2O2 Amorph. orangered solid. Source: Cyanobacterium Calothrix sp. (soil). Pharm: Anticancer-Cell-Effect (model: HeLa cells, mechanism: cell cycle inhibition; oxidative stress induction) (Chen, 2003); cytotoxic (MTT assay, HeLa); cytotoxic (MTT assay, CEM, IC50 = 0. 20–5.13 μmol/L); poison of DNA topoisomerase I; cell cycle effects (producer of G1 arrest, 0.1 μmol/L); antiplasmodial (CRPF, IC50 = 180 nmol/L). Ref: R. W. Rickards, et al, Tetrahedron, 1999, 55, 13513│X. X. Chen, et al, J. Appl. Phycol. 2003, 15, 269│P. H. Bernardo, et al, BoMCL, 2007, 17, 82│Q. A. Khan, et al, JNP 2009, 72, 438 O N N H O

907 Canogramide Type: Miscellaneous tetra-and higher-cyclic alkaloids. C24H21N3O4 Source: Marinederived bacterium Actinoalloteichus cyanogriseus (sediment, China). Pharm: Multidrug resistance reversing agents. Ref: P. Fu, et al, Org. Lett., 2014, 16, 3708 O O N N

N O

O

908 Circumdatin F Type: Miscellaneous tetra-and higher-cyclic alkaloids. C17H13N3O3 Source: Deep-sea fungus Aspergillus westerdijkiae DFFSCS013 (South China Sea). Pharm: Antifoulant (Bugula neritina larval settlement, EC50 = 8.81 μg/mL, LC50 > 200 μg/mL, LC50/ EC50 > 24.7). Ref: X. Zhang, et al, J. Ind. Microbiol. Biotechnol., 2014, 41, 741

346

10 Steroidal and Miscellaneous Alkaloids

O N O

O N H

N

909 Circumdatin L Type: Miscellaneous tetra-and higher-cyclic alkaloids. C17H13N3O3 Source: Deep-sea fungus Aspergillus westerdijkiae DFFSCS013 (South China Sea). Pharm: Antifoulant (Bugula neritina larval settlement, EC50 = 34.91 μg/mL, LC50 > 200 μg/mL, LC50/ EC50 > 5.73). Ref: X. Zhang, et al, J. Ind. Microbiol. Biotechnol., 2014, 41, 741

O N O

O N H

N

910 Citrinadin B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C28H39N3O4 Pale yellow solid, [α]D20 = +8° (c = 1, MeOH). Source: Marine-derived fungus Penicillium citrinum N-059 from brown alga Actinotrichia fragilis. Pharm: Cytotoxic (L1210, IC50 = 10 μg/mL). Ref: M. Tsuda, et al, Org. Lett., 2004, 6, 3087│T. Mugishima, et al, JOC, 2005, 70, 9430│K. Kong, et al, JACS, 2013, 135, 10890 (structure revised).

O OH O

HN

H

14

N O

HN

911 Communesin A Commindoline B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C28H32N4O2 Amorph. powder, mp 194–196 °C, mp > 300 °C, [α]D20 = −174° (c = 1.34, CHCl3). Source: Marine-derived fungus Penicillium sp. OUPS-79 from green alga Enteromorpha intestinalis, terrestrial Penicillium expansum MK-57. Pharm: Cytotoxic (P388, ED50 = 3.5 μg/ mL); insecticidal. Ref: A. Numata, et al, Tet. Lett., 1993, 34, 2355│C. Iwamoto, et al, Tetrahedron, 1999, 55, 14353

10.2 Miscellaneous Alkaloids

347

O H

H

O

H

N

N

15

N H

H

N

912 Communesin B Commindoline A; Nomofungin Type: Miscellaneous tetra-and higher-cyclic alkaloids. C32H36N4O2 Amorph. powder, mp 165–170 °C, mp 152–154 °C, [α]D22 = +8.7° (c = 0.2, CHCl3), [α]D20 = −74.9° (c = 1.5, CHCl3). Source: Marine-derived fungus Penicillium sp. OUPS-79 from green alga Enteromorpha intestinalis, terrestrial Penicillium expansum MK-57. Pharm: Cytotoxic (P388, ED50 = 0.45 μg/mL); mycotoxin; insecticide. Ref: A. Numata, et al, Tet. Lett., 1993, 34, 2355│C. Iwamoto, et al, Tetrahedron, 1999, 55, 14353│A. S. Ratnayake, et al, JOC, 2001, 66, 8717; 2003, 68, 1640 O H N

H

N

O

H

15

N H

H

N

913 Communesin C Type: Miscellaneous tetra-and higher-cyclic alkaloids. C31H34N4O2 [α]D = −30° (c = 0.04, MeOH). Source: Marine-derived fungus Penicillium sp. from sponge Axinella verrucosa (Mediterranean Sea). Pharm: Cytotoxic (leukemia cell lines U937, THP-1, NAMALWA, L-428, Molt3, and SUP-B15, moderate antiproliferative). Ref: R. Jadulco, et al, JNP, 2004, 67, 78│CRC Press, DNP on DVD, 2012, versiom 20.2 O H N

H

N

15

N H

N H H

H

O

348

10 Steroidal and Miscellaneous Alkaloids

914 Communesin D Communesin C‡ Type: Miscellaneous tetra-and higher-cyclic alkaloids. C32H34N4O3 Amorph. powder, mp 190–195 °C, [α]D = +23.3° (c = 0.04, MeOH), [α]D20 = +150° (c = 0.14, CHCl3). Source: Marine-derived fungus Penicillium sp. from sponge Axinella verrucosa (Mediterranean Sea), fungus Penicillium expansum Link MK-57 (Japan waters). Pharm: Cytotoxic (leukemia cell lines U937, THP-1, NAMALWA, L-428, Molt3, and SUP-B15, moderate antiproliferative); insecticidal (silkworm larvae). Ref: R. Jadulco, et al, JNP, 2004, 67, 78│H. Hayashi, et al, Biosci. Biotechnol. Biochem., 2004, 68, 753│CRC Press, DNP on DVD, 2012, versiom 20.2 O H N

H

N

H

O

15

N H

H

N O

915 Communesin E Communesin D‡ Type: Miscellaneous tetra-and higher-cyclic alkaloids. C27H30N4O2 Amorph. powder, mp 250 °C (dec), [α]D20 = −156° (c = 0.11, CHCl3). Source: Fungus Penicillium expansum Link MK-57 (Japan waters). Pharm: Insecticidal (silkworm larvae). Ref: H. Hayashi, et al, Biosci. Biotechnol. Biochem., 2004, 68, 753 O N

H

H

N H H

H O

N

N H

916 Communesin F Communesin E‡ Type: Miscellaneous tetra-and higher-cyclic alkaloids. C28H32N4O Amorph. powder, mp 144–147 °C, [α]D20 = −264° (c = 0.34, CHCl3). Source: Fungus Penicillium expansum Link MK-57 (Japan waters). Pharm: Insecticidal (silkworm larvae). Ref: H. Hayashi, et al, Biosci. Biotechnol. Biochem., 2004, 68, 753

10.2 Miscellaneous Alkaloids

O N

349

H

H N

N H H

N

917 Cottoquinazoline C Type: Miscellaneous tetra-and higher-cyclic alkaloids. C26H25N5O4 Source: Marinederived fungus Aspergillus versicolor MST-MF495 and LCJ-5-4 from soft coral Cladiella sp. (South China Sea). Pharm: Antifungal (yeast Candida albicans, modest). Ref: L. J. Fremlin, et al, JNP, 2009, 72, 666│Zhuang, Y.et al, Org. Lett., 2011, 13, 1130 O N H

N

N H

H

OH NH

N

H O

O

918 Cottoquinazoline D Type: Miscellaneous tetra-and higher-cyclic alkaloids. C24H19N5O4 Source: Marinederived fungus Aspergillus versicolor MST-MF495 and LCJ-5-4 from soft coral Cladiella sp. (South China Sea). Pharm: Antifungal (Candida albicans, MIC = 22.6 μmol/L). Ref: L. J. Fremlin, et al, JNP, 2009, 72, 666│Zhuang, Y.et al, Org. Lett., 2011, 13, 1130 O N N N

H

H

OH NH

N H O

O

350

10 Steroidal and Miscellaneous Alkaloids

919 Cystodimine A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C18H12N4O Source: Ascidian Cystodytes dellechiajei (green coloured specimens, Cabo de Gata, Southern Spain, Mediterranean). Pharm: Antibacterial (Escherichia coli and Micrococcus luteus, MIC = 1.1–10.5 μg/mL). Ref: N. Bontemps, et al, JNP, 2010, 73, 1044 N

H N

N NH

O

920 Cystodimine B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C18H12N4O2 Source: Ascidian Cystodytes dellechiajei (green coloured specimens, Cabo de Gata, Southern Spain, Mediterranean). Pharm: Antibacterial (Escherichia coli and Micrococcus luteus, MIC = 1.1–10.5 μg/mL). Ref: N. Bontemps, et al, JNP, 2010, 73, 1044 N HO

H N

N NH

O

921 N-Deacetylshermilamine B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C19H16N4OS Source: Ascidian Cystodytes dellechiajei (green coloured specimens, Cabo de Gata, Southern Spain, Mediterranean; purple coloured specimens, Catalonia, Northwestern Spain, Mediterranean). Pharm: Antibacterial (Escherichia coli and Micrococcus luteus, MIC = 1. 1–10.5 μg/mL). Ref: N. Bontemps, et al, JNP, 2010, 73, 1044 N H N

N H

S

NH2

O

10.2 Miscellaneous Alkaloids

351

922 Densanin A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C33H49N2O3 Source: Sponge Haliclona densaspicula (Keomun I., R.O.Korea). Pharm: NO production inhibitor (LPS-stimulated BV2 monoglial cells). Ref: B. S. Hwang, et al, Org. Lett., 2012, 14, 6154 O H N

+

HO

N H H O

923 Densanin B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C32H51N2O3 Source: Sponge Haliclona densaspicula (Keomun I., R.O.Korea). Pharm: NO production inhibitor (LPSstimulated BV2 monoglial cells). Ref: B. S. Hwang, et al, Org. Lett., 2012, 14, 6154 O H N

+

HO

N H H O

924 Dictyodendrine A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C43H34N2O11S Amorph. red solid (Na salt), [α]D19 = −4.6° (c = 0.01, MeOH/0.3M NaClO4) (Na salt). Source: Sponge Dictyodendrilla verongiformis (Japan waters). Pharm: Telomerase inhibitor. Ref: K. Warabi, et al, JOC, 2003, 68, 2765 O OH

O HO N HO N HO

OH

H

O

S O

O OH

352

10 Steroidal and Miscellaneous Alkaloids

925 Dictyodendrine B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C41H30N2O10S Amorph. yellow solid (Na salt). Source: Sponge Dictyodendrilla verongiformis (Japan waters). Pharm: Telomerase inhibitor. Ref: K. Warabi, et al, JOC, 2003, 68, 2765 OH

O HO N HO N OH

O

H

HO

O

S

OH

O

926 Dictyodendrine C Type: Miscellaneous tetra-and higher-cyclic alkaloids. C34H24N2O9S Greenish-yellow solid (Na salt). Source: Sponge Dictyodendrilla verongiformis (Japan waters). Pharm: Telomerase inhibitor. Ref: K. Warabi, et al, JOC, 2003, 68, 2765 OH O N HO

4' 7

N O

O

H

HO

O

S

OH

O

927 Dictyodendrine D Type: Miscellaneous tetra-and higher-cyclic alkaloids. C34H24N2O12S2 Greenishyellow solid (Na salt). Source: Sponge Dictyodendrilla verongiformis (Japan waters). Pharm: Telomerase inhibitor. Ref: K. Warabi, et al, JOC, 2003, 68, 2765 OH O HO O O S O

N 4' 7

N HO

O

H

O

S O

O OH

10.2 Miscellaneous Alkaloids

353

928 Dictyodendrine E Type: Miscellaneous tetra-and higher-cyclic alkaloids. C41H39N2O9S Amorph. red solid (Na salt) Source: Sponge Dictyodendrilla verongiformis (Japan waters). Pharm: Telomerase inhibitor. Ref: K. Warabi, et al, JOC, 2003, 68, 2765 O

HO

S O

O OH

NH

O N

OH

HO OH

929 Dictyodendrine F Type: Miscellaneous tetra-and higher-cyclic alkaloids. C34H24N2O6 Source: Sponge Ianthella sp. CMB-01245 (Bass Strait, Australia). Pharm: Protease β-secretase (BACE) inhibitor; cytotoxic (SW620 and P-glycoprotein over-expressing SW620 Ad300); anti-Alzheimer‘s agents (potential). Ref: H. Zhang, et al, RSC Adv., 2012, 2, 4209 HO

H N

O OH

N OH O HO

930 Dictyodendrine G Type: Miscellaneous tetra-and higher-cyclic alkaloids. C35H26N2O6 Source: Sponge Ianthella sp. CMB-01245 (Bass Strait, Australia). Pharm: Cytotoxic (SW620 and Pglycoprotein over-expressing SW620 Ad300). Ref: H. Zhang, et al, RSC Adv., 2012, 2, 4209

354

O

10 Steroidal and Miscellaneous Alkaloids

H N

O OH

N OH O

HO

931 Dictyodendrine H Type: Miscellaneous tetra-and higher-cyclic alkaloids. C34H23BrN2O6 Source: Sponge Ianthella sp. CMB-01245 (Bass Strait, Australia). Pharm: Protease β-secretase (BACE) inhibitor; cytotoxic (SW620 and P-glycoprotein over-expressing SW620 Ad300); antiAlzheimer‘s agents (potential). Ref: H. Zhang, et al, RSC Adv., 2012, 2, 4209 HO

H N

O OH

N OH O

HO

Br

932 Dictyodendrine I Type: Miscellaneous tetra-and higher-cyclic alkaloids. C34H23IN2O6 Source: Sponge Ianthella sp. CMB-01245 (Bass Strait, Australia). Pharm: Protease β-secretase (BACE) inhibitor; cytotoxic (SW620 and P-glycoprotein over-expressing SW620 Ad300); anti-Alzheimer‘s agents (potential). Ref: H. Zhang, et al, RSC Adv., 2012, 2, 4209 HO

H N

O OH

N OH O HO

I

933 Dictyodendrine J Type: Miscellaneous tetra-and higher-cyclic alkaloids. C34H24N2O8 Source: Sponge Ianthella sp. CMB-01245 (southern Australia). Pharm: Protease β-secretase (BACE) inhibitor. Ref: H. Zhang, et al, RSC Advances, 2012, 2, 4209

10.2 Miscellaneous Alkaloids

355

OH HO NH O O O

O

N

OH

OH

934 Dihydroingenamine D Type: Miscellaneous tetra-and higher-cyclic alkaloids. C28H44N2O Source: An unidentified sponge (order Haplosclerida, family Petrosiidae, Coral Sea, Queensland, Australia). Pharm: Antiplasmodial (Plasmodium falciparum, various strains, low ng/mL range). Ref: M. Ilias, et al, PM, 2012, 78, 1690 H N H

H N OH

935 Divergolide A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C31H39NO8 Source: Mangrovederived streptomycete Streptomyces sp. from mangrove Bruguiera gymnorrhiza (stem). Pharm: Cytotoxic; antibacterial (Bacillus subtilis and Mycobacterium vaccae). Ref: L. Ding, et al, Angew. Chem., Int. Ed., 2011, 50, 1630

H

O

OH

O O O

NH

O OH

O

356

10 Steroidal and Miscellaneous Alkaloids

936 Divergolide C Type: Miscellaneous tetra-and higher-cyclic alkaloids. C31H35NO8 Source: Mangrovederived streptomycete Streptomyces sp. from mangrove Bruguiera gymnorrhiza (stem). Pharm: Cytotoxic; antibacterial (Bacillus subtilis and Mycobacterium vaccae). Ref: L. Ding, et al, Angew. Chem., Int. Ed., 2011, 50, 1630 OH

O

H N

HO OH

O

O

O

OH

937 Divergolide D Type: Miscellaneous tetra-and higher-cyclic alkaloids. C31H35NO8 Source: Mangrovederived streptomycete Streptomyces sp. from mangrove Bruguiera gymnorrhiza (stem). Pharm: Cytotoxic; antibacterial (Bacillus subtilis and Mycobacterium vaccae). Ref: L. Ding, et al, Angew. Chem., Int. Ed., 2011, 50, 1630

O O

H

O

HO

NH

OH

HO O O

938 Granulatimide Type: Miscellaneous tetra-and higher-cyclic alkaloids. C15H8N4O2 Yellow solid. Source: Ascidian Didemnum granulatum (Brazil). Pharm: G2 specific cell cycle checkpoint inhibitor. Ref: R. G. S. Berlinch, et al, JOC, 1998, 63, 9850 H N

O

O

H N N H

N

10.2 Miscellaneous Alkaloids

357

939 Grossularine 1 Type: Miscellaneous tetra-and higher-cyclic alkaloids. C23H18N6O Amorph. yellow powder, mp 350 °C, first example of a naturally occurring α-carboline Source: Ascidian Dendrodoa grossularia. Pharm: Cytotoxic (L1210, IC50 = 6 μg/mL). Ref: C. Moquin, et al, Tet. Lett., 1984, 25, 5047│C. Moquin-Pattey, et al, Tetrahedron, 1989, 45, 3445│S. Achab, et al, Tet. Lett., 1993, 34, 2127│T. Choshi, et al, Synlett, 1995, 147│T. Choshi, et al, JOC, 1995, 60, 5899

N N

H N

NH

N

N H

O

940 Grossularine 2 Type: Miscellaneous tetra-and higher-cyclic alkaloids. C21H17N5O2 Crystal (THF/ MeOH), mp 281–283 °C; mp 197 °C. Source: Ascidian Dendrodoa grossularia. Pharm: Antineoplastic (hmn solid carcinoma: WiDr and MCF7); cytotoxic (L1210, IC50 = 4 μg/ mL). Ref: C. Moquin-Pattey, et al, Tetrahedron, 1989, 45, 3445│S. Achab, et al, Tet. Lett., 1993, 34, 2127│T. Choshi, et al, Synlett, 1995, 147│T. Choshi, et al, JOC, 1995, 60, 5899

N N NH

N H

OH

N O

941 (–)-Haliclonadiamine Type: Miscellaneous tetra-and higher-cyclic alkaloids. C25H40N2 mp 115–117 °C, [α]D = 18.2°. Source: Sponge Haliclona sp. Pharm: Antimicrobial. Ref: E. Fahy, et al, Tet. Lett., 1988, 29, 3427│A. G. M. Barrett, et al, J. Chem. Soc., Chem. Commun., 1994, 1881│G. -Y. -S. Wang, et al, Tet. Lett., 1996, 37, 1813 H

H N

H N

H H

H H H

H

H

358

10 Steroidal and Miscellaneous Alkaloids

942 Haliclonine A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C32H48N2O4 Gum, [α]D20 = −23.6° (c = 0.14, MeOH). Source: Sponge Haliclona sp. (Jeju I., R. O. Korea). Pharm: Antibacterial (Staphylococcus aureus ATCC 6538p, MIC = 25 μg/mL, Bacillus subtilis ATCC 6633, MIC = 6.25 μg/mL, Micrococcus luteus IFO 12708, MIC = 12.5 μg/mL, Proteus vulgaris ATCC 3851, MIC = 12.5 μg/mL, Escherichia coli ATCC 25922, MIC > 100 μg/mL); cytotoxic (K562, IC50 = 15.9 μg/mL (0.03 mmol/L)). Ref: K. H. Jang, et al, Org. Lett., 2009, 11, 1713

HO N O

O

H

N

O

943 Hamigeran D Type: Miscellaneous tetra-and higher-cyclic alkaloids. C21H26BrNO2 Pale yellow solid, [α]D25 = −47.1° (c = 0.21, CH2Cl2). Source: Sponge Hamigera tarangaensis. Pharm: Cytotoxic. Ref: K. D. Wellington, et al, JNP, 2000, 63, 79

N

O

O

Br

H

944 22-Hydroxyingamine A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C30H44N2O2 Source: An unidentified sponge (order Haplosclerida, family Petrosiidae, Coral Sea, Queensland, Australia). Pharm: Antiplasmodial (Plasmodium falciparum, various strains, low ng/mL range). Ref: M. Ilias, et al, PM, 2012, 78, 1690

10.2 Miscellaneous Alkaloids

359

H N

H

H

N OH

OH

945 4-Hydroxy-1’,3,4’-tri(4-hydroxyphenyl)-3’-[2-(4-hydroxyphenyl)ethyl]-7’(sulfooxy)spiro[furan-2(5H),2’(3’H)-pyrrolo[2,3-c]carbazole]- 5,5’(6’H)-dione Type: Miscellaneous tetra-and higher-cyclic alkaloids. C43H30N2O12S Purple solid (Na salt), mp > 300 °C (Na salt), racemic. Source: Sponge Dictyodendrilla sp. (Japan waters) Pharm: Aldose reductase inhibitor. Ref: A. Sato, et al, JOC, 1993, 58, 7632 O O

S

HO

OH

O NH

O

O

O N

HO

OH OH OH

946 Ileabethoxazole Type: Miscellaneous tetra-and higher-cyclic alkaloids. C21H27NO2 Pale yellow oil, [α]D20 = +6.8° (c = 1, CHCl3). Source: Gorgonian Pseudopterogorgia elisabethae. Pharm: Antituberculosis (Mycobacterium tuberculosis H37Rv, 4 μg/mL, InRt = 29%, 8 μg/mL InRt = 38%, 16 μg/mL InRt = 54%, 32 μg/mL, InRt = 73%, 64–128 μg/mL, InRt = 92%; MIC = 61 μg/mL, control Rifampin, MIC = 0.1 μg/mL). Ref: I. I. Rodríguez, et al, Tetrahedron Lett. 2006, 47, 3229 OH

H

N O

360

10 Steroidal and Miscellaneous Alkaloids

947 Ingamine A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C30H44N2O Colorless glass, [α]D = +131° (c = 0.8, MeOH). Source: Sponge Xestospongia ingens (Papua New Guinea). Pharm: Cytotoxic. Ref: F. Kong, et al, Tetrahedron, 1994, 50, 6137; 1995, 51, 2895

N OH N

948 Ingamine B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C30H44N2 Glass, [α]D = +105° (c = 0.5, MeOH). Source: Sponge Xestospongia ingens. Pharm: Cytotoxic (P388). Ref: F. Kong, et al, Tetrahedron, 1994, 50, 6137; 1995, 51, 2895

N

N

949 Ingenamine Type: Miscellaneous tetra-and higher-cyclic alkaloids. C26H40N2O Amorph. solid, [α]D = +62° (c = 0.14, MeOH). Source: Sponge Xestospongia ingens (Papua New Guinea). Pharm: Cytotoxic. Ref: F. Kong, et al, Tet. Lett., 1994, 35, 1643 N

OH N

950 Ingenamine G Type: Miscellaneous tetra-and higher-cyclic alkaloids. C32H50N2O Glassy solid, [α]D29 = −59.2° (c = 0.05, MeOH). Source: Sponge Pachychalina sp. (Brazil). Pharm: Cytotoxic (HCT8, B16, and MCF7); antibacterial (Staphylococcus aureus ATCC 25923,

10.2 Miscellaneous Alkaloids

361

Escherichia coli ATCC 25922, and four oxacilin-resistant Staphylococcus aureus strains); antituberculosis (Mycobacterium tuberculosis H37Rv). Ref: J. H. H. L. De Oliveira, et al, JNP, 2004, 67, 1685

OH N H N

951 Isogranulatimide Type: Miscellaneous tetra-and higher-cyclic alkaloids. C15H8N4O2 Deep purple cryst. (MeCN aq) or amorph. red solid. Source: Ascidians Didemnum conchyliatum (Bahamas) and Didemnum granulatum (Brazil). Pharm: G2 specific cell cycle checkpoint inhibitor (in vitro, IC50 = 1.0–1.8 μmol/L). Ref: R. G. S. Berlinch, et al, JOC, 1998. 63, 9850│H. C. Vervoort, et al, JNP, 1999, 62, 389│E. Piers, et al, JOC, 2000, 65, 530 H N

O

O

N

N

N H

952 Keramaphidin B Deoxyingenamine Type: Miscellaneous tetra-and higher-cyclic alkaloids. C26H40N2 Amorph. solid, [α]D = +29.8° (c = 1.1, MeOH). Source: Sponges Xestospongia ingens and Amphimedon sp. (Okinawa). Pharm: Cytotoxic (P388, IC50 = 0.28 μg/mL, KB, IC50 = 0.3 μg/mL). Ref: J. Kobayashi, et al, Tet. Lett., 1994, 35, 4383│M. Tsuda, et al, Tetrahedron, 1996, 52, 2319│J. Kobayashi, et al, Tet. Lett., 1996, 37, 8203│J. E. Baldwin, et al, Angew. Chem. Int. Ed., 1998, 37, 2661│J. E. Baldwin, et al, Chem. Eur J., 1999, 5, 3154 N

N

362

10 Steroidal and Miscellaneous Alkaloids

953 Madangamine A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C30H44N2 Glass, [α]D = +319° (c = 1, EtOAc). Source: Sponge Xestospongia ingens (Papua New Guinea). Pharm: Cytotoxic (P388, ED50 = 0.93 μg/mL; hmn lung A549, ED50 = 14 μg/mL; brain U373, ED50 = 5.1 μg/mL; breast MCF7, ED50 = 5.17 μg/mL). Ref: F. Kong, et al, JACS, 1994, 116, 6007

N N H

954 37-(Methoxycarbonyl)dictyodendrine E Type: Miscellaneous tetra-and higher-cyclic alkaloids. C43H32N2O11S Purple solid, mp > 300 °C. Source: Sponge Dictyodendrilla sp. (Japan waters) Pharm: Aldose reductase inhibitor. Ref: A. Sato, et al, JOC, 1993, 58, 7632 O O HO

S OH O

NH O O

O N

OH

HO

OH

955 N-Methoxymethylisocystodamine Type: Miscellaneous tetra-and higher-cyclic alkaloids. C10H14N4O2 Source: Sponge Biemna sp. (Oshima-Shinsone, Japan). Pharm: Inducer of erythroid differentiation (hmn leukaemia cells, potent). Ref: R. Ueoka, et al, Tetrahedron, 2011, 67, 6679

10.2 Miscellaneous Alkaloids

363

N N

N O

NH

O

956 N1-Methyldibromoisophakellin Type: Miscellaneous tetra-and higher-cyclic alkaloids. C12H13Br2N5O Source: Sponge Stylissa caribica (Bahamas). Pharm: Antifeedant (reef fish Thalassoma bifasciatum). Ref: M. Assmann, et al, JNP, 2001, 64, 1345 Br

Br H N

H

N

H2 N N

N

O

957 N-Methylisocystodamine Type: Miscellaneous tetra-and higher-cyclic alkaloids. C19H12N4O Source: Sponge Biemna sp. (Oshima-Shinsone, Japan). Pharm: Inducer of erythroid differentiation (hmn leukaemia cells, potent). Ref: R. Ueoka, et al, Tetrahedron, 2011, 67, 6679

N N

N NH

O

958 Neosurugatoxin Type: Miscellaneous tetra-and higher-cyclic alkaloids. C30H34BrN5O15 Prisms +1 H2O (H2O), mp 331–335 °C (dec). Source: Prosobranch (Japanese ivory shell) Babylonia japonica (digestive gland), bacterium Corynebacterium sp. Pharm:

364

10 Steroidal and Miscellaneous Alkaloids

Antimydriatic (powerful); insecticide; nematocide. Ref: T. Kosuge, et al, Tet. Lett., 1981, 22, 3417│T.Kosuge, et al, CPB, 1985, 33, 3059│S. Inoue, et al, Tetrahedron, 1994, 50, 2729│S. Inoue, et al, Tetrahedron, 1994, 50, 2753 OH

OH HO

O

HO

O OH O

Br

OH O H N

H

OH

H N

O NH

H

N OH

N H

O

O

959 Ningalin A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C18H9NO8 Amorph. yellow solid, [α]D = 0° (c = 0.5, 10% DMSO/MeOH). Source: Sponge Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005); ascidian Didemnum sp. (Western Australia). Pharm: Binding capacity to HIV-1 targets (20 μg/ mL, using BIAcore instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/mm2) = 11.7). Ref: H. Kang, et al, JOC, 1997, 62, 3254│D. L. Boger, et al, JACS, 1999, 121, 54│G. Fan, et al, BoMC, 2010, 18, 5466 HO

OH

HO

O

O

OH

O N H

O

960 Ningalin D Type: Miscellaneous tetra-and higher-cyclic alkaloids. C40H27NO12 Dark red solid, [α]D = 0° (c = 0.025, MeOH). Source: Ascidian Didemnum sp. (Western Australia). Pharm: Kinases inhibitors CK1δ, CDK5 and GSK3β (potent). Ref: H. Kang, et al, JOC, 1997, 62, 3254│F. Plisson, et al, Chem Med Chem, 2012, 7, 983

10.2 Miscellaneous Alkaloids

HO

OH

HO

365

OH

O

O N

HO

OH HO

3''

OH

OH OH

961 Ningalin G Type: Miscellaneous tetra-and higher-cyclic alkaloids. C40H27NO12 Source: Ascidian Didemnum sp. (Northern Rottnest Shelf, Western Australia). Pharm: Kinases inhibitors CK1δ, CDK5 and GSK3β (potent). Ref: F. Plisson, et al, Chem Med Chem, 2012, 7, 983 HO

HO

OH

HO O

O N

HO HO

HO

OH OH OH

962 Norzoanthamine Type: Miscellaneous tetra-and higher-cyclic alkaloids. C29H39NO5 Cryst., mp 282–285 °C, [α]D = +1.6° (c = 1, CHCl3). Source: Zoanthid Zoanthus sp. (Ayamaru coast of Amami Is., Japan). Pharm: Osteoporosis inhibitor (suppresses decreases in bone weight and strength in ovariectomized mice, could be a good candidate for an osteoporotic drug); cytotoxic (P388, IC50 = 24 μg/mL). Ref: S. Fukuzawa, et al, Heterocycl. Commun., 1995, 1, 207│M. Kuramoto, et al, Bull. Chem. Soc. Jpn., 1998, 71, 771│M. Kuramoto, et al, Mar. Drugs, 2004, 2, 39

366

10 Steroidal and Miscellaneous Alkaloids

O H O 17

H

15 26

H 11

O

N

O

O 3 30

963 epi-Norzoanthamine Type: Miscellaneous tetra-and higher-cyclic alkaloids. C29H41NO5 Collorlessoil, [α]D = +67.4° (c = 0.19, CHCl3). Source: Zoanthid Zoanthus sp. (Ayamaru coast of Amami Is., Japan). Pharm: Cytotoxic (P388, IC50 = 24 μg/mL). Ref: S. Fukuzawa, et al, Heterocycl. Commun., 1995, 1, 207│M. Kuramoto, et al, Bull. Chem. Soc. Jpn., 1998, 71, 771│M. Kuramoto, et al, Mar. Drugs, 2004, 2, 39 OH H O 17S

H H

N

O O

O

964 Norzoanthaminone Type: Miscellaneous tetra-and higher-cyclic alkaloids. C29H37NO6 Collorlessoil. Source: Zoanthid Zoanthus sp. (Ayamaru coast of Amami Is., Japan). Pharm: Cytotoxic (P388, IC50 = 1.0 μg/mL); IL-6 inhibitor; osteoporosis inhibitor. Ref: S. Fukuzawa, et al, Heterocycl. Commun., 1995, 1, 207│M. Kuramoto, et al, Bull. Chem. Soc. Jpn., 1998, 71, 771│M. Kuramoto, et al, Mar. Drugs, 2004, 2, 39

10.2 Miscellaneous Alkaloids

367

O H O H H O N

O O

O

965 Oxazinin A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C58H62N2O10 Source: Marinederived unidentified fungus (Eurotiomycetes class) from ascidian Lissoclinum patella (Papua New Guinea). Pharm: Antimycobacterial Ref: Z. Lin, et al, Org. Lett., 2014, 16, 4774

OH O

HO

NH

O

O H

N

O O

O OH

O

966 (–)-Papuamine Type: Miscellaneous tetra-and higher-cyclic alkaloids. C25H40N2 Mp 167.5–169 °C, [α]D = −150° (c = 1.5, MeOH). Source: Sponge Holiclona sp. (Pacific Ocean). Pharm: Antifungal; antimicrobial. Ref: E. Fahy, et al, Tet. Lett., 1988, 29, 3427│A. G. M. Barrett, et al, J. Chem. Soc., Chem. Commun., 1994, 1881 H N

H N H

H H

H

368

10 Steroidal and Miscellaneous Alkaloids

967 Prosurugatoxin Type: Miscellaneous tetra-and higher-cyclic alkaloids. C25H26BrN5O11 Source: Prosobranch (Japanese ivory shell) Babylonia japonica. Pharm: Ganglion blocking agent; phycotoxin; mydriatic agent. Ref: T.Kosuge, et al, CPB, 1985, 33, 3059 O

H N O

NH N

NH OH

HO

H

O

OH

O O

N H

Br

OH

HO OH

968 Pseudonocardian A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C18H18N2O5 White solid, [α]D20 = +1.52° (c = 0.46, MeOH). Source: Marine-derived bacterium Pseudonocardia sp. SCSIO 01299 (depth of 3258 m, deep sea sediment, South China Sea, 120°0.975′E 19°0.664′N). Pharm: Cytotoxic (SF268, IC50 = 0.028 μmol/L, control Cisplatin, IC50 = 3.99 μmol/L; MCF7, IC50 = 0.027 μmol/L, Cisplatin, IC50 = 9.24 μmol/L; NCIH460, IC50 = 0.209 μmol/L, Cisplatin, IC50 = 1.53 μmol/L); antibacterial (Bacillus thuringiensis SCSIO BT01, MIC = 4 μg/mL; Staphylococcus aureus ATCC 29213, MIC = 4 μg/ mL; Enterococcus faecalis, ATCC 29212, MIC = 2 μg/mL). Ref: S. Li, et al, Mar. Drugs, 2011, 9, 1428 O

O HO

N

N

O

OH

969 Pseudonocardian B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C19H20N2O5 White solid, [α]D20 = −1.56° (c = 0.90, MeOH). Source: Marine-derived bacterium Pseudonocardia sp. SCSIO 01299 (depth of 3258 m, deep sea sediment, South China Sea, 120°0.975′E 19°0.664′N). Pharm: Cytotoxic (SF268, IC50 = 0.022 μmol/L, control Cisplatin, IC50 = 3.99 μmol/L; MCF7, IC50 = 0.021 μmol/L, Cisplatin, IC50 = 9.24 μmol/L; NCI-H460, IC50 = 0.177 μmol/L, Cisplatin, IC50 = 1.53 μmol/L); antibacterial (Bacillus thuringiensis SCSIO BT01, MIC = 2 μg/mL; Staphylococcus aureus ATCC 29213, MIC = 2 μg/mL;

10.2 Miscellaneous Alkaloids

369

Enterococcus faecalis, ATCC 29212, MIC = 2 μg/mL). Ref: S. Li, et al, Mar. Drugs, 2011, 9, 1428 O

O HO

N

N

O

OH

970 Pseudonocardian C Type: Miscellaneous tetra-and higher-cyclic alkaloids. C21H24N2O8 Red brown powder, [α]D25 = −25.6° (c = 0.16, MeOH). Source: Marine-derived bacterium Pseudonocardia sp. SCSIO 01299 (depth of 3258 m, deep sea sediment, South China Sea, 120°0.975′E 19°0.664′N). Pharm: Cytotoxic (SF268, IC50 = 6.70 μmol/L, control Cisplatin, IC50 = 3.99 μmol/L; MCF7, IC50 = 8.02 μmol/L, Cisplatin, IC50 = 9.24 μmol/L; NCIH460, IC50 = 43.28 μmol/L, Cisplatin, IC50 = 1.53 μmol/L); antibacterial (Bacillus thuringiensis SCSIO BT01, MIC > 128 μg/mL; Staphylococcus aureus ATCC 29213, MIC > 128 μg/mL; Enterococcus faecalis, ATCC 29212, MIC > 128 μg/mL). Ref: S. Li, et al, Mar. Drugs, 2011, 9, 1428

O HO HO HO

N H

N O

O

O

OH

971 Purpurone Type: Miscellaneous tetra-and higher-cyclic alkaloids. C40H27NO11 Purple glass. Source: Sponges Iotrochota baculifera (depth of 8 m, inner coral reef, Hainan I., South China Sea, Oct. 2005) and Iotrochota sp. Pharm: Multidrug reversal activity (antifungal of Brefeldin A in presence of 30 μmol/L alkaloid Purpurone, Candida albicans sensitive GU4 strain, MIC = 12.5 μg/mL, negative control 1% DMSO, MIC = 6.3 μg/mL; Candida albicans resistant GU5 strain, MIC = 25 μg/mL, negative control 1% DMSO, MIC = 50 μg/mL); anti-HIV-1 IIIB (p24 antigen detection assay, MT4 cells, IC50 > 25 μg/mL); anti-HIV-1 IIIB (MAGI test (single life cycle), MAGI (Hela-CD4-LTR-β-gal indicator cells), IC50 > 25 μg/mL); binding capacity to HIV-1 targets (20 μg/mL, using BIAcore instrument instrument: recombinant protein Vif (viral infectivity factor of HIV-1), binding capacity RU (response unit, 1 RU = 1 pg/ mm2) = −25.7; recombinant protein hmn APOBEC3G (innate intracellular anti-viral

370

10 Steroidal and Miscellaneous Alkaloids

factor), RU = −26.3; recombinant protein gp41 (trans-membrane protein of HIV-1), RU = −23.0); lipogenesis inhibitor; ATP-citrate lyase inhibitor;antioxidant (DPPH scavenger, IC50 = 7 μmol/L). Ref: G. W. Chan, et al, JOC, 1993, 58, 2544│Y. Liu, et al, Z. Naturforsch. C, 2008, 63, 63│G. Fan, et al, BoMC, 2010, 18, 5466 HO

OH HO

OH

O

O N HO

OH HO

OH

OH

972 Thorectandramine Type: Miscellaneous tetra-and higher-cyclic alkaloids. C27H24N3O31+ Yellow solid (NH4+ salt), [α]D = +4.9° (c = 0.08, MeOH) (NH4+ salt). Source: Sponge Thorectandra sp. (Palau, Oceania) Pharm: Cytotoxic (MCF7, OVCAR-3, A549, weak). Ref: R. D. Charan, et al, Tet. Lett., 2002, 43, 5201

N

+

N

H HO

OH

N H OH

973 Tsitsikammamine C Type: Miscellaneous tetra-and higher-cyclic alkaloids. C20H20N3O2 Source: Sponge Zyzzya sp., (Rodda Reef, Queensland). Pharm: Antiplasmodial (inhibits both CSPF and CRPF, very low nmol/L level); cytotoxic (strong). Ref: R. A. Davis, et al, JMC, 2012, 55, 5851

10.2 Miscellaneous Alkaloids

371

O H N

N

N

+

OH

974 Variecolortide A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C39H35N3O7 Yellow cryst. (MeOH), mp 182 °C (dec), [α]D25 = +5.5° (c = 0.1, CHCl3). Source: Fungus Aspergillus variecolor B-17 (sediments, Mngolian Jilantai Salt Field, China). Pharm: Cytotoxic (K562, IC50 = 61 μmol/L); antioxidant (DPPH scavenger, weak); caspase-3 inhibitor. Ref: W. -L. Wang, et al, Chem. Biodiversity, 2007, 4, 2913│G. -D. Chen, et al, Fitoterapia, 2014, 92, 252 HO O OH

HO

H N

O

O

O N H

N H

975 Variecolortide B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C34H27N3O7 Amorph. yellow powder, [α]D25 = +4.1° (c = 0.1, CHCl3). Source: Fungus Aspergillus variecolor B-17 (sediments, Mngolian Jilantai Salt Field, China). Pharm: Cytotoxic (K562, IC50 = 69 μmol/L); antioxidant (DPPH scavenger, weak); caspase-3 inhibitor. Ref: W. -L. Wang, et al, Chem. Biodiversity, 2007, 4, 2913│G. -D. Chen, et al, Fitoterapia, 2014, 92, 252

372

10 Steroidal and Miscellaneous Alkaloids

HO O OH

HO

H N

O

O

O N H

N H

976 Variecolortide C Type: Miscellaneous tetra-and higher-cyclic alkaloids. C35H29N3O7 Amorph. yellow powder, [α]D25 = +4° (c = 0.1, CHCl3). Source: Fungus Aspergillus variecolor B-17 (sediments, Mngolian Jilantai Salt Field, China). Pharm: Cytotoxic (K562, IC50 = 71 μmol/L); antioxidant (DPPH scavenger, weak); caspase-3 inhibitor. Ref: W. -L. Wang, et al, Chem. Biodiversity, 2007, 4, 2913│G. -D. Chen, et al, Fitoterapia, 2014, 92, 252 O O OH

HO

H N

O

O

O N H

N H

977 Venezueline B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C14H14N2O4 Source: Marine-derived streptomycete Streptomyces venezuelae (sediment, Guam) Pharm: Cytotoxic (panel of HTCLs: HCT8, IC50 = 5.74 μmol/L, control 5-FU, IC50 = 5.38 μmol/L, BGC823, IC50 = 6.78 μmol/L, 5-FU, IC50 = 3.84 μmol/L, A549, IC50 = 7.52 μmol/L, 5-FU, IC50 = 1.54 μmol/L, A2780, IC50 = 6.57 μmol/L, 5-FU, IC50 = 5.40 μmol/L, Bel7402, IC50 > 10 μmol/L, 5-FU, IC50 = 3.85 μmol/L, NCIH460, IC50 = 9.67 μmol/L, 5-FU, IC50 = 7.12 μmol/L). Ref: J. Ren, et al, Bioorg. Med. Chem. Lett., 2013, 23, 301

10.2 Miscellaneous Alkaloids

373

HO H

O

O HO

N H

N

978 Waikialoid A Type: Miscellaneous tetra-and higher-cyclic alkaloids. C52H54N6O7 Source: Fungus Aspergillus sp. Pharm: Antifungal (Candida albicans, biofilm inhibition assay, dosedependent, IC50 = 1.4 μmol/L) Ref: X. R. Wang, et al, JNP, 2012, 75, 707 –

O N

O

O

N

+

O

N H O

N

H

O

H N H

N O

979 Waikialoid B Type: Miscellaneous tetra-and higher-cyclic alkaloids. C52H54N6O9 Source: Fungus Aspergillus sp. Pharm: Antifungal (Candida albicans, biofilm inhibition assay, dosedependent, IC50 = 46.3 μmol/L) Ref: X. R. Wang, et al, JNP, 2012, 75, 707 –

O N

O

O

N

+

O

N H O

N

H

O

OH H N

N O

+ –

O

Index 1 Compound Name and Synonym Index This index lists in alphabetical order all active compound’s 1,090 entry names including both 979 key names and 111 synonym names contained in the bodies of compound entries. A equal sign ( = ) and compound code number (from 1 to 979) follow the name immediately for locating the compound in the “Handbook of Active Marine Natural Products Volume 4” 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 Aaptamine = 460. Aaptosine = 836. 2-Acetamido-8-(hydroxymethyl)-3H-phenoxazin3-one = 805. 4-Acetoxyplakinamine B = 780. 4-Acetyl-6-methyl-2(1H)-pyridinone = 256. Adenine = 644. Aerophobin 1 = 74. Aerophobin 2 = 75. Aerothionin = 76. Aflatoxin = 513. Agelongine = 177. (–)-Ageloxime D = 645. Agrochelin = 114. Almazole C = 1. Almazole D = 2. Alotamide A = 153. Amaminol A = 817. Amaminol B = 818. 2-Amino-8-benzoyl-6-hydroxy-3H-phenoxazin3-one = 799. 4-Amino-5-bromo-pyrrolo[2,3-d]pyrimidine = 511. 7-Amino-7-demethoxymimosamycin = 439. 1-Aminodiscorhabdin D = 325. 2-Amino-6-hydroxy-3H-phenoxazin-3-one = 800. 9-Aminoisoascididemnin = 387. 4-Aminomimosamycin = 440. 2-Amino-3H-phenoxazin-3-one = 801. Ammosamide A = 837. Ammosamide D = 307. Amphimedine = 388. Anguibactin = 115. Aniquinazoline A = 470. Aniquinazoline B = 471.

https://doi.org/10.1515/9783110653908-008

Aniquinazoline C = 472. Aniquinazoline D = 619. Antibiotic PF 1140 = 178. Antibiotic ZZF 51 = 179. Aphrocallistin = 646. Aplidiopsamine A = 838. Aplysina archeri Alkaloid = 77. Aplysinamisine I = 78. Aplysinamisine II = 79. Aplysinamisine III = 80. Ar11 = 693. Ar4 = 695. Ar9 = 694. Aragupetrosine A = 298. Araguspongine A = 306. Araguspongine B = 299. (+)-Araguspongine D = 300. Araguspongine E = 301. Araplysillin 1 = 81. Araplysillin 2 = 82. Araplysillin I = 81. Araplysillin II = 82. Archerine = 83. Ariakemicin A = 3. Ariakemicin B = 4. Arnoamine A = 389. Arnoamine B = 390. Arnoamine C = 391. Arnoamine D = 392. Ascididemin = 393. Aspernigrin B = 180. Aspeverin = 889. Aspidostomide E = 514. Asporyzin A = 890. Asporyzin B = 891. Asporyzin C = 892. Auranomide A = 480.

376

Index 1 Compound Name and Synonym Index

Auranomide B = 481. Auranomide C = 482. Auranthine = 893. Aurantiomide B = 839. Aurantiomide C = 840. Ax10 = 670. Ax9 = 671. Axinyssimide A = 708. Axinyssimide B = 709. Axinyssimide C = 710. Axiplyn C = 677. Axiplyn D = 678. Axiplyn E = 679. (+)-Axisonitrile 3 = 689. (‒)-Axisonitrile 3 = 690. 10-epi-Axisonitrile 3 = 691. Axisothiocyanate 2 = 695. (+)-Axisothiocyanate 3 = 692. Axistatin 1 = 483. Axistatin 2 = 484. Axistatin 3 = 485. (Z)-Azacyclo-6-undecene = 833. Azaspiracid 1 = 269. Azaspiracid 2 = 270. Azaspiracid 4 = 271. Azaspiracid 5 = 272. Azaspiracid 6 = 273. B Bacillamide A = 116. Baculiferin A = 894. Baculiferin B = 895. Baculiferin C = 896. Baculiferin D = 897. Baculiferin E = 898. Baculiferin F = 899. Baculiferin G = 900. Baculiferin H = 901. Baculiferin I = 841. Baculiferin J = 842. Baculiferin K = 843. Baculiferin L = 902. Baculiferin M = 903. Baculiferin N = 844. Baculiferin O = 904. Barbamide = 117. Barbital = 486. Batzelline B = 326. Batzelline C = 327.

Bengazole A = 5. Bengazole B = 6. Bengazole C = 7. Bengazole C4 = 8. Bengazole C6 = 9. Bengazole D = 10. Bengazole E = 11. Bengazole F = 12. Bengazole G = 13. Bengazole Z = 14. Benzoxacystol = 797. Bi2 = 707. Biemnadin = 394. Biemnidin = 521. Bioxalomycin α1 = 592. Bioxalomycin α2 = 593. Bioxalomycin β1 = 594. Bioxalomycin β2 = 595. Botryllazine B = 515. Brevianamide M = 845. 14-Bromo-7,8-didehydro-3-dihydrodiscorhabdin C = 328. 14-Bromodihydrodiscorhabdin C = 329. 4-Bromodihydrodiscorhabdin C = 330. 14-Bromodiscorhabdin C = 331. 2-Bromolavanducyanin = 564. 2-Bromoleptoclinidinone = 395. 2-Bromo-5-(2-methyl-2-butylene)phenazinone = 565. C Ca13 = 681. Ca2 = 680. Ca21 = 682. Ca22 = 688. Ca3 = 686. Ca34 = 677. Caboxamycin = 28. Caerulomycin = 181. Caerulomycin A = 181. Caerulomycinamide = 182. Caerulomycin C = 183. Caerulomycin F = 184. Caerulomycin G = 185. Caerulomycin H = 186. Caerulomycin I = 187. Caerulomycin J = 188. Caerulomycin K = 189. Caerulomycinonitrile = 190.

Index 1 Compound Name and Synonym Index

Caissarone = 647. Callophycin A = 846. Calothrixin A = 905. Calothrixin B = 906. Canogramide = 907. Carboxyexfoliazone = 802. 1-Carboxymethylnicotinic acid = 191. 2-Carboxy-1-methylpyridinium betaine = 224. (‒)-Cavernothiocyanate = 670. Cephalostatin 1 = 761. Cephalostatin 2 = 762. Cephalostatin 3 = 763. Cephalostatin 4 = 764. Cephalostatin 5 = 765. Cephalostatin 6 = 766. Cephalostatin 7 = 767. Cephalostatin 8 = 768. Cephalostatin 9 = 769. Cephalostatin 10 = 770. Cephalostatin 11 = 771. Cephalostatin 12 = 772. Cephalostatin 13 = 773. Cephalostatin 14 = 774. Cephalostatin 15 = 775. Cephalostatin 16 = 776. Cephalostatin 17 = 777. Cephalostatin 18 = 778. Cephalostatin 19 = 779. Ceratinamide A = 84. Ceratinamide B = 85. Chaetominedione = 847. Chandrananimycin C = 803. Chandrananimycin D = 804. Chelonin A = 798. Chrysogine = 473. Circumdatin F = 908. Circumdatin L = 909. Citrinadin B = 910. Cladoquinazoline = 620. epi-Cladoquinazoline = 621. Clavatadine C = 86. Clavatadine D = 87. Clavatadine E = 88. Clavepictine A = 293. Clavepictine B = 294. Commindoline A = 912. Communesin A = 911. Communesin B = 912. Communesin C = 913.

Communesin C‡ = 914. Communesin D = 914. Communesin D‡ = 915. Communesin E = 915. Communesin E‡ = 916. Communesin F = 916. Convolutamine J = 487. Cortistatin A = 756. Cortistatin B = 757. Cortistatin C = 758. Cortistatin D = 759. Cortistatin J = 760. Corydendramine A = 274. Corydendramine B = 275. Coscinolactam A = 746. Coscinolactam B = 747. Cottoquinazoline C = 917. Cottoquinazoline D = 918. CPB48-974-7 = 192. CPB48-974-8 = 193. Crambescin A1 = 488. Crambescin A2 = 489. Crambescin B = 490. Crambescin B1 = 491. Crambescin C1 = 492. Crambine B = 490. Cribochaline A = 194. Cribrochalinamine oxide A = 195. Cribrochalinamine oxide B = 196. Cribrostatin 1 = 441. Cribrostatin 2 = 442. Cribrostatin 3 = 443. Cribrostatin 4 = 596. Cribrostatin 5 = 444. Cribrostatin 6 = 445. Curacin A = 118. Curacin B = 119. Curacin C = 120. Curacin D = 121. Cyanogriside A = 197. Cyanogriside B = 198. Cyanogriside C = 199. Cyclodercitine = 396. Cyclodidemniserinol = 819. Cyclostellettamine A = 200. Cyclostellettamine B = 201. Cyclostellettamine C = 202. Cyclostellettamine D = 203. Cyclostellettamine E = 204.

377

378

Index 1 Compound Name and Synonym Index

Cyclostellettamine F = 205. Cycloxazoline = 33. Cylindrospermopsin = 848. Cystodamine = 397. Cystodimine A = 919. Cystodimine B = 920. Cystodytin A = 398. Cystodytin B = 399. Cystodytin J = 400. D Damirone B = 332. Damirone C = 333. N-Deacetylkuanoniamine D = 401. N-Deacetylshermilamine B = 921. (R)-6-Debromohamacanthin B = 516. (R)-6″-Debromohamacanthin B = 517. 6-(1,3-Decadienyl)octahydro-4-methyl-2Hquinolizin-3-ol = 294. 10-Dechlorodysideathiazole = 122. 10-Dechloro-N-methyldysideathiazole = 123. Dehydrokuanoniamine B = 402. Dehydrokuanoniamine F = 403. 9-De-O-methylaaptamine = 461. 4-O-Demethylbarbamide = 124. Demethylisodysidenin = 125. Demethyloxyaaptamine = 462. O-Demethylrenierol acetate = 446. O-Demethylrenierone = 447. Dendrodoine = 160. Densanin A = 922. Densanin B = 923. Deoxyamphimedine = 404. 12-Deoxyascididemin = 405. Deoxyingenamine = 952. Deoxynortryptoquivaline = 474. Deoxynyboquinone = 849. Deoxy-penipanoid C = 493. 1′-Deoxypsammaplysin D = 85. Deoxytryptoquivaline = 475. Dercitamide = 416. Dercitamine = 406. Dercitin = 407. Dermacozine A = 566. Dermacozine B = 567. Dermacozine C = 568. Dermacozine D = 569. Dermacozine E = 570. Dermacozine F = 571.

Dermacozine G = 572. Desmethylphidolopin = 648. 1,5-Diazacycloheneicosane = 827. Diazonamide A = 34. Diazonamide C = 35. Diazonamide D = 36. Diazonamide E = 37. Dictyodendrine A = 924. Dictyodendrine B = 925. Dictyodendrine C = 926. Dictyodendrine D = 927. Dictyodendrine E = 928. Dictyodendrine F = 929. Dictyodendrine G = 930. Dictyodendrine H = 931. Dictyodendrine I = 932. Dictyodendrine J = 933. (3S,5R)-6ʹ,6″Didebromo-3,4dihydrohamacanthin B = 518. (S)-6ʹ,6″-Didebromohamacanthin A = 519. (R)-6ʹ,6″-Didebromohamacanthin B = 520. 9,10-Didechloro-N-methyldysideathiazole = 126. Didehydrocrambescin A1 = 494. 7,8-Didehydro-3-dihydrodiscorhabdin C = 334. Didymellamide A = 206. 3-Dihydrodiscorhabdin B = 335. Dihydrodiscorhabdin C = 336. Dihydrohalichondramide = 38. 8,9-Dihydro-11-hydroxyascididemin = 408. Dihydroingenamine D = 934. 5,10-Dihydrophencomycin methyl ester = 573. 24,25-Dihydroplakinamine A = 781. Dihydroplakinamine K = 782. 4,7-Dihydroxy-8-methoxyquinoline = 308. 3,7-Dimethylisoguanine = 649. 1,3-Dimethylisoguanine (1997) = 650. Diplamine = 409. Discoipyrrole A = 850. Discoipyrrole B = 851. Discoipyrrole C = 828. Discoipyrrole D = 852. Discorhabdin A = 337. Discorhabdin B = 338. Discorhabdin C = 339. (+)-(2S,6R,8S)-Discorhabdin D = 340. Discorhabdin E = 341. Discorhabdin G‡ = 342. Discorhabdin G‡ = 343. (+)-Discorhabdin I = 343.

Index 1 Compound Name and Synonym Index

(–)-Discorhabdin L = 344. (–)-(1R,2S,6R,8S)-Discorhabdin N = 345. Discorhabdin P = 346. (−)-(6S,8R)-Discorhabdin Q = 347. Discorhabdin R = 348. Discorhabdin S = 349. Discorhabdin T = 350. Discorhabdin U = 351. Discorhabdin V = 352. (S,S)-Discorhabdin W = 353. (R,R)-Discorhabdin W = 354. Discorhabdin Y = 355. (−)-Discorhabdin Z = 356. Divergolide A = 935. Divergolide B = 853. Divergolide C = 936. Divergolide D = 937. 6-(1,3,5,9-Dodecatetraenyl)-2-methyl3-piperidinol = 274. Dolabellin = 127. Dolastatin 18 = 128. Dolastatin E = 162. Dragmacidin = 521. Dragmacidin E = 522. Drimentine G = 713. (4E,S)-Dysidazirine = 829. (4E,R)-(–)-Dysidazirine = 830. Dysideathiazole = 129. Dysidenin = 130. E Echinoclathrine A = 207. Echinoclathrine B = 208. Echinoclathrine C = 209. Ecionine A = 410. Ecionine B = 411. Ecteinascidin 583 = 597. Ecteinascidin 594 = 598. Ecteinascidin 729 = 599. Ecteinascidin 736 = 600. Ecteinascidin 743 = 601. Ecteinascidin 745 = 602. Ecteinascidin 759B = 603. Ecteinascidin 770 = 604. Eilatin = 412. Enigmazole A = 15. Ep5 = 697. Epinardine A = 357. Epinardine C = 358.

Epipolasinthiourea B = 696. Erythrazole B = 145. Essramycin = 175. Eu11 = 673. Eu17 = 676. Eu20 = 674. Eu24 = 675. Eu27 = 672. Exfoliazone = 805. F Farneside A = 711. Fasciospongine A = 748. Fasciospongine B = 749. Fasciospongine C = 750. Fascularine = 291. Fistularin 3 = 89. 11-epi-Fistularin 3 = 90. 4-Formamidoeudesm-7-ene = 672. (–)-N-Formyl-1,2-dihydrorenierone = 448. N-Formylpsammaplysin A = 84. Fu1 = 744. Fu12 = 743. Fu13 = 742. Fu16 = 678. Fu17 = 679. Fumiquinazoline A = 622. Fumiquinazoline B = 623. Fumiquinazoline C = 624. Fumiquinazoline D = 625. Fumiquinazoline E = 626. Fumiquinazoline F = 627. Fumiquinazoline G = 628. Fumiquinazoline H = 629. Fumiquinazoline I = 630. Fumiquinazoline J = 631. Fumiquinazoline L (Zhou, 2013) = 632. Fumiquinazoline S = 633. Fumitremorgin C = 634. G GB4 Toxin = 829. Geranylphenazinediol = 574. Glucopiericidin C = 210. Glycinylilimaquinone = 737. Granulatimide = 938. Griseoluteic acid = 575. Grossularine 1 = 939. Grossularine 2 = 940.

379

380

Index 1 Compound Name and Synonym Index

Gymnodimine = 854. Gymnodimine B = 855. H Halichlorine = 295. Halichonadin C = 673. Halichondramide = 39. Haliclamine C = 211. Haliclamine D = 212. Haliclona 3-Alkylpyridinium dimer = 213. Haliclona 3-Alkylpyridinium trimer = 214. Haliclonacyclamine A = 276. Haliclonacyclamine B = 277. (–)-Haliclonadiamine = 941. Haliclonine A = 942. Haliclorensin = 831. Halicyclamine B = 278. Halimedin = 832. Halishigamide A = 40. Halishigamide B = 41. Halishigamide C = 42. Halishigamide D = 43. Halochonadin F = 693. Halytulin = 309. (S)-Hamacanthin A = 523. (S)-Hamacanthin B = 524. Hamigeran D = 943. Haminol 1 = 215. Haminol 2 = 216. Haminol 3 = 217. Haminol 4 = 218. Haminol 5 = 219. Haminol 6 = 220. Haminol A = 221. Haminol B = 222. Haminol C = 223. Hanishin racemic methyl ester = 560. Haouamine A = 856. Haouamine B = 857. Helquinoline = 310. (–)-Hennoxazole A = 16. Hennoxazole B = 17. O10-Hexadecanoyl-deacylbengazole C = 13. Hippolide A = 751. Hoiamide D = 131. Homarine = 224. Homoaerothionin = 91. Homocrambescin A2 = 495. Homocrambescin B1 = 496.

Homocrambescin C1 = 497. 11-Hydroxyaerothionin = 92. Hydroxyakalone = 498. 19-Hydroxyaraplysillin N20-sulfamate = 93. 11-Hydroxyascididemin = 397. 2-(4-Hydroxybenzoyl) quinazolin-4(3H)-one = 477. 2-(4-Hydroxybenzyl) quinazolin-4(3H)-one = 493. 5S-Hydroxy-5,6-dihydrohalichondramide = 48. 3-Hydroxyglyantrypine = 635. 22S-Hydroxyhalichondramide = 49. 22-Hydroxyhaliclonacyclamine B = 279. 4-Hydroxy-7-[1-hydroxy-2-(methylamino)ethyl]-2 (3H)-benzothiazolone = 146. 4-Hydroxy-1-(3-hydroxyphenyl)-3(2H)isoquinolinone = 449. 22-Hydroxyingamine A = 944. 9-Hydroxyisoascididemnin = 413. (11S)-Hydroxyl aspergillic acid = 525. 30-Hydroxy-lobatamide A = 824. 6-(Hydroxymethyl)-1-phenazinecarboxamide = 576. 2-Hydroxy-1ʹ-methylzeatin = 651. 32-Hydroxymycalolide A = 44. 30-Hydroxymycalolide A = 45. 38-Hydroxymycalolide B = 46. 12R-Hydroxy-11-oxoaerothionin = 94. 19-Hydroxypsammaplysin E = 95. 4-Hydroxy-1ʹ,3,4ʹ-tri(4-hydroxyphenyl)-3ʹ-[2-(4hydroxyphenyl)ethyl]-7ʹ-(sulfooxy)spiro [furan-2(5H),2ʹ(3ʹH)-pyrrolo[2,3-c] carbazole]-5,5ʹ(6ʹH)-dione = 945. Hyrtioseragamine A = 526. Hyrtioseragamine B = 527. I Ikimine A = 225. Ikimine B = 226. Ikimine C = 227. Ikimine D = 228. Ileabethoxazole = 946. 2-(3-Indolyl)-6-(3,4,5-trimethoxyphenyl) morpholine = 798. Indosespene = 714. Ingamine A = 947. Ingamine B = 948. Ingenamine = 949. Ingenamine G = 950.

Index 1 Compound Name and Synonym Index

Irregularasulfate = 752. Isoaaptamine = 463. Isobatzelline A = 359. Isobatzelline B = 360. Isobatzelline C = 361. Isobatzelline D = 362. Isochaetominine A = 636. Isochaetominine B = 637. Isochaetominine C = 638. 14-epi-Isochaetominine C = 639. (–)-10-Isocyano-4-amorphene = 680. 10-Isocyano-4-cadinene = 681. (1S*,4S*,7R*,10S*)-10-Isocyano-5-cadinen-4-ol = 682. 10-Isocyano-5-cadinen-4-ol = 683. 10-Isocyano-5-cadinen-4-ol = 684. (‒)-(1S,2R,5S,8R)-2-Isocyanoclovane = 742. (‒)-(1S,5S,8R)-2-Isocyanoclovene = 743. 9-Isocyanopupukeanane = 698. 9-epi-9-Isocyanopupukeanane = 699. 2-Isocyanopupukeanane = 700. 3-Isocyanotheonellin = 707. 2-Isocyanotrachyopsane = 744. Isodysidenin = 132. Isogranulatimide = 951. Isohalichondramide = 47. (–)-Isopuloupone = 229. Isosaraine 1 = 296. (1R,4S,5S,6R,7S,10R)-(+)Isothiocyanatoalloaromadendrane = 694. 10-isothiocyanato-4,6-amorphadiene = 685. (–)-10-Isothiocyanato-4-amorphene = 686. 4-Isothiocyanato-9-amorphene = 687. 10-Isothiocyanatoamorph-5-en-4-ol = 688. 4-Isothiocyanato-9-cadinene = 687. 4-Isothiocyanato-7α-eudesm-11-ene = 674. 4-Isothiocyanato-7β-eudesm-11-ene = 675. 7-Isothiocyanato-11-oppositene = 671. (–)-9-Isothiocyanatopupukaenane = 701. 9-Isothiocyanatopupukeanane = 702. 11-Isothiocyano-7βH-eudesm-5-ene = 676. J Jaspisamide A = 48. Jaspisamide B = 49. Jaspisamide C = 50. JBIR 34 = 18. JBIR 35 = 19. Jorumycin = 605.

K Kabiramide A = 51. Kabiramide B = 52. Kabiramide C = 53. Kabiramide C acetate = 54. Kabiramide D = 55. Kabiramide E = 56. Kabiramide G = 57. Kabiramide J = 58. Kabiramide K = 59. Kabiramide L = 60. Kalkitoxin = 133. Kasarin = 528. Keramaphidin B = 952. Keramaphidin C = 833. Killarytoxin 3 = 269. Kimbasine A = 753. Kimbasine B = 754. Kuanoniamine A = 414. Kuanoniamine B = 415. Kuanoniamine C = 416. Kuanoniamine D = 417. L Labuanine A = 418. Latrunculin A = 148. Latrunculin B = 149. Latrunculin C = 150. Latrunculin D = 151. Latrunculin S = 152. Lavanducyanin = 577. Leiodelide A = 61. Leiodelide B = 62. Leiodolide A = 61. Leiodolide B = 62. Lepadin A = 311. (–)-Lepadin B = 312. Lepadoformine = 292. Leptoclinidinone = 393. Leucascandrolide A = 20. Lipoxazolidinone A = 21. Lipoxazolidinone B = 22. Lissoclinamide 1 = 163. Lissoclinamide 4 = 164. Lissoclinamide 5 = 165. Lissoclinamide 6 = 166. Lobatamide A = 821. Lobatamide A 24E-isomer = 823. Lobatamide A 26Z-isomer = 822.

381

382

Index 1 Compound Name and Synonym Index

Lobatamide B = 822. Lobatamide C = 823. Lobatamide D = 824. Lodopyridone = 134. Lokysterolamine A = 783. Lokysterolamine B = 784. (S)-Longamide A = 561. Longamide B = 562. Lumichrome = 667. M Ma’edamine A = 529. Madangamine A = 953. Maedamine A = 529. Maedamine B = 530. Makaluvamine A = 363. Makaluvamine B = 364. Makaluvamine C = 365. Makaluvamine D = 366. Makaluvamine E = 367. Makaluvamine F = 368. Makaluvamine G = 369. Makaluvamine H = 370. Makaluvamine I = 371. Makaluvamine J = 372. Makaluvamine K = 373. Makaluvamine L = 374. Makaluvamine M = 375. Makaluvamine N = 376. Makaluvamine P = 377. Makaluvone = 378. Malonganenone A = 652. Malonganenone D = 653. Malonganenone E = 654. Malonganenone I = 655. Malonganenone J = 656. Marinoquinoline A = 313. Martefragine A = 23. Mayotamide A = 154. Mayotamide B = 155. Mechercharmycin A = 167. Mechercharstatin A = 167. Meridianin A = 499. Meridianin B = 500. Meridianin C = 501. Meridianin D = 502. Meridianin E = 503. Meridianin F = 504. Meridianin G = 505.

Meridine = 419. N-[4-(Methoxycarbonylamino)-2-oxobutyl]-7, 9-dibromo-10-hydroxy-8-methoxy-1-oxa2-azaspiro[4.5]deca-2,6,8-triene-3carboxylic acid amide = 96. 37-(Methoxycarbonyl)dictyodendrine E = 954. 7-Methoxy-1,6-dimethyl-5,8-isoquinolinedione = 450. N-Methoxymethylisocystodamine = 955. N-Methoxy-16-(3-pyridinyl)-7-hexadecyn1-amine = 244. N-Methoxy-16-(3-pyridinyl)-5-hexadecyn1-amine = 245. N4-Methylaaptamine = 464. 5-Methylaeruginol = 140. 3ʹ-Methylaminoavarone = 715. 4ʹ-Methylaminoavarone = 716. 2-Methylbenzothiazole = 147. N1-Methyldibromoisophakellin = 956. 33-Methyldihydrohalichondramide = 63. N13-Methyl-discorhabdin C = 346. N-Methyldysideathiazole = 135. 33R-Methylhalichondramide = 50. 1-Methylherbipoline = 657. 1-Methyl-6-iminopurine = 658. N-Methylisocystodamine = 957. N1-Methylmanzacidin C = 506. N-Methylnorsalsolinol = 451. N3-Methyl-4-oxo-3-epi-plakinamine B = 785. 2-(1-Methyl-2-oxopropylidene) phosphorohydrazidothioate oxime = 820. O10-(13-Methylpentadecanoyl)-deacylbengazole C = 12. β-Methyl-3-pyridinedodecanal O-methyloxime = 226. 4-Methyl-3H-pyrrolo[2,3-c]quinoline = 313. 24-Methylritterazine D = 536. N30-Methyl-23ξ,24ξ,25,30tetrahydroplakinamine A = 786. N3′-Methyltetrahydrovariolin B = 858. O10-(12-Methyltridecanoyl)-deacylbengazole C = 10. Methyl-3,4,5-trimethoxy-2-(2-(nicotinamido) benzamido)benzoate = 230. 22-O-(N-Me-L-valyl)-21-epiaflaquinolone B = 314. Microbiaeratinin = 116. Microxine = 659. Mimosamycin = 452.

Index 1 Compound Name and Synonym Index

Monanchomycalin A = 859. Monanchomycalin B = 860. Monodontamide F = 476. 3-(4-Morpholinyl)demethyloxyaaptamine = 465. Mucronatine = 660. Mycalolide A = 64. Mycalolide C = 65. Mycalolide D = 66. Mycalolide E = 67. Mycothiazole = 136. N Nagelamide Z = 168. Nakijinamine A = 861. Nakijinamine B = 862. Nakijinamine C = 29. Nakijinamine E = 30. Nakijinamine F = 863. Nakijinol B = 31. Nakijinol B diacetate = 717. Nakijiquinone A = 718. Nakijiquinone B = 719. Nakijiquinone C = 720. Nakijiquinone D = 721. Nakijiquinone G = 722. Nakijiquinone H = 723. Nakijiquinone I = 724. Nakijiquinone N = 725. Nakijiquinone O = 726. Nakijiquinone P = 727. Nakijiquinone R = 728. Navenone A = 231. Neamphine = 834. Nemertelline = 232. Neoamphimedine = 420. Neopeltolide = 24. Neopetrosiamine A = 280. Neosurugatoxin = 958. New Aspergillic acid = 531. Nicotinamide = 233. Ningalin A = 959. Ningalin B = 864. Ningalin C = 865. Ningalin D = 960. Ningalin G = 961. Niphatesine A = 234. Niphatesine B = 235. (S)-Niphatesine C = 236.

Niphatesine D = 237. Niphatesine E = 238. Niphatesine F = 239. Niphatesine G = 240. Niphatesine H = 241. Niphatoxin A = 242. Niphatoxin B = 243. Niphatyne A = 244. Niphatyne B = 245. Njaoaminium A = 246. Njaoaminium B = 247. Njaoaminium C = 248. Nocardichelin A = 25. Nocardichelin B = 26. Nomofungin = 912. 2-Nonyl-4-hydroxyquinoline N-oxide = 315. 2-Nonyl-4-quinolone = 316. Norcrambescin B1 = 507. Norcrambescin C1 = 508. Nordercitin = 421. Norquinadoline A = 640. Norzoanthamine = 962. epi-Norzoanthamine = 963. Norzoanthaminone = 964. Nostocyclamide = 169. Nostocyclamide M = 170. Nuttingine A = 661. Nuttingine B = 662. Nuttingine C = 663. Nuttingine D = 664. Nuttingine E = 665. O Oceanapamine = 712. Oceanapia Quinolone alkaloid = 97. 7-[(1,2,3,4,4a,7,8,8a-Octahydro-1,2,4a, 5-tetramethyl-1-naphthalenyl)methyl]6-benzoxazolol = 32. Oxazinin A = 965. Oxepinamide A = 866. 11-Oxoaerothionin = 98. 19-Oxofasciospongine A = 755. (14R)-Oxoglyantrypine = 641. (14S)-Oxoglyantrypine = 642. P Pantherinine = 422. (–)-Papuamine = 966. (–)-Pateamine A = 156.

383

384

Index 1 Compound Name and Synonym Index

Patellazole A = 157. Patellazole B = 158. Patellazole C = 159. Patellide = 158. Pelagiomicin A = 578. Pelagiomicin B = 579. Pelagiomicin C = 580. Penasulfate A = 281. Penicinolone = 317. Penipanoid A = 176. Penipanoid B = 867. Penipanoid C = 477. Penispirolloid A = 318. O10-Pentadecanoyl-deacylbengazole C = 11. 2-n-Pentyl-4(1H)-quinolinol = 319. Perfragilin A = 453. Perfragilin B = 454. Perophoramidine = 423. Petrosaspongiolide L = 249. Petrosine = 302. Petrosine A = 303. Petrosine B = 304. Phakellin = 563. Phenazine Alkaloid 1 = 581. Phenazine Alkaloid 2 = 582. Phenazine Alkaloid 3 = 583. Phenazine Alkaloid 4 = 584. 1,6-Phenazinedimethanol = 585. Phidolopin = 666. Phloeodictine A = 808. Phloeodictine A1 = 809. Phloeodictine A2 = 810. Phloeodictine A3 = 811. Phloeodictine A4 = 812. Phloeodictine A5 = 813. Phloeodictine A6 = 814. Phloeodictine A7 = 815. Phloeodictyne B = 816. Phomopsin A‡ = 449. Phorboxazole A = 68. Phorboxazole B = 69. Pileotin B = 250. Pinnaic acid = 282. Plakinamine A = 787. Plakinamine B = 788. Plakinamine C = 789. Plakinamine D = 790. Plakinamine E = 791. Plakinamine F = 792.

Plakinamine I = 793. Plakinamine J = 794. Plakinamine K = 795. Plakinamine M = 796. Poecillanosine = 825. (+)-epi-Polasin A = 697. epi-Polasin B = 695. epi-Polasinthiourea B = 696. Polycarpathiamine A = 161. Prianosin A = 337. Prianosin B = 379. Prianosin D = 340. Prosurugatoxin = 967. Psammaplysin A = 99. Psammaplysin B = 100. Psammaplysin C = 101. Psammaplysin D = 102. Psammaplysin E = 103. Psammaplysin H = 104. Psammopemmin A = 499. Psammopemmin B = 503. Psammopemmin C = 500. Pseudodistomin A = 283. Pseudodistomin B = 284. Pseudodistomin C = 285. Pseudodistomin D = 286. Pseudodistomin E = 287. Pseudodistomin F = 288. Pseudodysidenin = 137. Pseudonocardian A = 968. Pseudonocardian B = 969. Pseudonocardian C = 970. Pterocellin A = 868. Pterocellin B = 869. Pu12 = 704. Pu2 = 698. Pu3 = 699. Pu4 = 702. Pu5 = 705. Pu6 = 706. Pu7 = 700. Pulicatin A = 138. Pulicatin B = 139. Pulicatin C = 140. Pulicatin D = 141. Pulicatin E = 142. Purealidin B = 105. Purealidin J = 106. Purealidin K = 107.

Index 1 Compound Name and Synonym Index

Purealidin L = 108. Purealidin P = 109. Purealidin Q = 110. Purealidin R = 111. Purealidin S = 112. Purpurone = 971. Pyridinebetaine A = 251. Pyrinodemin A = 252. Pyrinodemin B = 253. Pyrinodemin C = 254. Pyrinodemin D = 255. Pyrostatin B = 509. Q Questiomycin A = 801. Quinadoline B = 643. 3ʹ-L-Quinovosyl saphenate = 581. 2ʹ-L-Quinovosyl saphenate = 582. R Renieramycin A = 606. Renieramycin B = 607. Renieramycin C = 608. Renieramycin D = 609. Renieramycin G = 610. Renieramycin H = 596. Renieramycin I = 611. Renieramycin M = 612. Renieramycin N = 613. Renieramycin O = 614. Renieramycin Q = 615. Renieramycin R = 616. Renieramycin S = 617. Renierol = 455. Renierone = 456. Reticulidin A = 729. Reticulidin B = 730. N-1-β-D-Ribofuranosyldamirone C = 380. N-1-β-D-Ribofuranosylmakaluvamine I = 381. Rigidin = 512. Ritterazine A = 532. Ritterazine B = 533. Ritterazine C = 534. Ritterazine D = 535. Ritterazine E = 536. Ritterazine F = 537. Ritterazine G = 538. Ritterazine H = 539. Ritterazine I = 540.

Ritterazine J = 541. Ritterazine K = 542. Ritterazine L = 543. Ritterazine M = 544. Ritterazine N = 545. Ritterazine O = 546. Ritterazine P = 547. Ritterazine Q = 548. Ritterazine R = 549. Ritterazine S = 550. Ritterazine T = 551. Ritterazine U = 552. Ritterazine V = 553. Ritterazine W = 554. Ritterazine X = 555. Ritterazine Y = 556. Ritterazine Z = 557. S Saldedine A = 457. Saldedine B = 458. Salinosporamide C = 870. Saraine 1 = 297. Schulzeine A = 871. Schulzeine B = 872. Schulzeine C = 873. Scytonemin = 874. Sebastianine A = 424. Sebastianine B = 425. Segoline A = 426. Sesbanimide = 289. Sesbanimide A = 289. Sespenine = 745. Shermilamine B = 427. Shermilamine C = 428. Shermilamine D = 429. Shermilamine E = 430. Shermilamine F = 431. Shewanelline C = 478. Smenospongiarine = 731. 5-epi-Smenospongiarine = 732. Smenospongidine = 733. 5-epi-Smenospongidine = 734. Smenospongine = 735. 5-epi-Smenospongine = 736. Smenospongine B = 737. Smenospongine C = 738. Smenospongorine = 739. 5-epi-Smenospongorine = 740.

385

386

Index 1 Compound Name and Synonym Index

Sp2 = 689. Sp3 = 692. Sp6 = 690. Sp8 = 691. Streptokordin = 256. Streptophenazine A = 586. Streptophenazine B = 587. Streptophenazine C = 588. Streptophenazine D = 589. Streptophenazine E = 590. Streptophenazine H = 591. Styelsamine A = 432. Styelsamine B = 433. Styelsamine C = 434. Styelsamine D = 435. Subereamolline A = 113. Suberitine A = 466. Suberitine B = 467. Suberitine C = 468. Suberitine D = 469. Sulcatin = 257. Symbioimine = 875. Synoxazolidinone C = 27.

Theonezolide B = 172. Theonezolide C = 173. 2-Thiocyanatoneopupukaenane = 703. 2-Thiocyanatoneopupukeanane = 704. 9-Thiocyanatopupukeanane = 705. 9-epi-Thiocyanatopupukeanane = 706. 1-Thiomethyldiscorhabdin I = 382. Thiomycalolide A = 70. Thiomycalolide B = 71. Thorectandramine = 972. Tintamine = 436. 4,4,4-Trichloro-3-methyl-N-[4,4,4-trichloro3-methyl-1-(2-thiazolyl)butyl]butanamide = 129. O10-Tridecanoyl-deacylbengazole C = 7. 4,5,8-Trihydroxy-2-quinolinecarboxylic acid = 320. Trikendiol = 741. Tryptoquivaline = 479. Tsitsikammamine A = 383. Tsitsikammamine B = 384. Tsitsikammamine C = 973. Tyrokeradine B (2009) = 321.

T Tauropinnaic acid = 290. Terreusinone = 876. 2,3,5,7-Tetrabromo-1H-benzofuro[3,2-b]pyrrole = 877. 5,6,9,10-Tetracarboxybenzo[b][1,8] naphthyridinium(1+) = 878. O4-Tetradecanoyl-bengazole Z = 8. O6-Tetradecanoyl-bengazole Z = 9. O10-Tetradecanoyl-deacylbengazole C = 5. 3,4,5,6-Tetrahydro-6-hydroxymethyl-3,6dimethylpyrimidine-4-carboxylic acid = 510. O,O,O′,O′-Tetrapropyl 2,2′-(1,2-dimethyl1,2-ethanediylidene)bis (phosphorohydrazidothioate) = 826. Tetroazolemycin A = 558. Tetroazolemycin B = 559. Thallusin = 258. Theoneberine = 459. Theonelladine A = 259. Theonelladine B = 260. Theonelladine C = 261. Theonelladine D = 262. Theonezolide A = 171.

U Ulapualide A = 72. Ulapualide B = 73. 2-Undecen-18-yl-4-quinolone = 322. 2-Undecyl-4-quinolone = 323. Untenine A = 263. Untenine B = 264. Untenine C = 265. Urochordamine A = 668. Urochordamine B = 669. Urukthapelstatin A = 174. Usabamycin A = 879. Usabamycin B = 880. Usabamycin C = 881. V Varamine A = 437. Varamine B = 438. Variecolortide A = 974. Variecolortide B = 975. Variecolortide C = 976. Variolin A = 882. Variolin B = 883. Veiutamine = 385. Venezueline A = 806.

Index 1 Compound Name and Synonym Index

Venezueline B = 977. Venezueline E = 807. Viridicatol = 324. Viscosaline = 266. Viscosamine = 267. Vitamin B3 = 233. Vitamin B4 = 644. W Waikialoid A = 978. Waikialoid B = 979. Wakayin = 386. Watasemycin A = 143. Watasemycin B = 144. Westiellamide = 33.

X Xestomycin = 618. Xestospongin A = 300. Xestospongin B = 305. Xestospongin C = 301. Xestospongin D = 306. Xylogranatopyridine A = 268. Xylopyridine A = 884. Z Zarzissine = 835. Zyzzyanone A = 885. Zyzzyanone B = 886. Zyzzyanone C = 887. Zyzzyanone D = 888.

387

Index 2 Compound Molecular Formula Index The Molecular Formula Index of Volume 4 lists the molecular formulae of all 979 active isolated compounds from marine organisms given in the HAMNP Volume 4 in Hill convention order. Under a bold formula, all related compound names following code numbers are listed in the code number order too. C5 C5H5N5 – Adenine, 644 – Zarzissine, 835 C5H5N5O2 – Hydroxyakalone, 498 C6 C6H5BrN4 – 4-Amino-5-bromo-pyrrolo[2,3-d]pyrimidine, 511 C6H5N3OS – Neamphine, 834 C6H6N2O – Nicotinamide, 233 C6H7N5 – 1-Methyl-6-iminopurine, 658 C6H10N2O2 – Pyrostatin B, 509 C6H20N4O5 – Suberitine B, 467 – Suberitine D, 469 C7 C7H6Br2N2O2 – (S)-Longamide A, 561 C7H7NO2 – Homarine, 224 C7H9N5O – 3,7-Dimethylisoguanine, 649 – 1,3-Dimethylisoguanine (1997), 650 – Mucronatine, 660 C8 C8H7NO4 – 1-Carboxymethylnicotinic acid, 191 C8H7NS – 2-Methylbenzothiazole, 147 C8H9NO2 – Streptokordin, 256

C8H9NO3 – Pyridinebetaine A, 251 C8H11N5O – Caissarone, 647 C8H11N5O4S – Microxine, 659 C8H12N2O3 – Barbital, 486 C8H12N5O – 1-Methylherbipoline, 657 C8H14N2O3 – 3,4,5,6-Tetrahydro-6-hydroxymethyl-3, 6-di-methylpyrimidine-4-carboxylic acid, 510 C9 C9H7N3O2S – Polycarpathiamine A, 161 C9H8Br2N2O3 – Longamide B, 562 C10 C10H3Br4NO – 2,3,5,7-Tetrabromo-1H-benzofuro[3,2-b] pyrrole, 877 C10H7NO5 – 4,5,8-Trihydroxy-2-quinolinecarboxylic acid, 320 C10H8N2O2 – Damirone C, 333 C10H9BrN3O1+ – Makaluvamine N, 376 C10H9NO3 – 4,7-Dihydroxy-8-methoxyquinoline, 308 C10H10Br2N2O3 – Hanishin racemic methyl ester, 560 C10H10Br2N2O4 – Purealidin R, 111 C10H10N2O2 – Chrysogine, 473

Index 2 Compound Molecular Formula Index

C10H10N3O1+ – Makaluvamine I, 371 C10H12N2O3S – 4-Hydroxy-7-[1-hydroxy-2-(methylamino) ethyl]-2(3H)-benzothiazolone, 146 C10H13NO2 – Sulcatin, 257 – N-Methylnorsalsolinol, 451 C10H14N4O2 – N-Methoxymethylisocystodamine, 955 C10H16N6O – Halimedin, 832 C10H19N – Keramaphidin C, 833 C10H22N3O3PS – GB4 Toxin, 820 C11 C11H9ClN2O2 – Batzelline C, 327 C11H9ClN2O2S – Batzelline B, 326 C11H9NO2S – Pulicatin D, 141 C11H9N3O2 – Caerulomycin H, 186 C11H10BrN2O2 – Makaluvone, 378 C11H10ClN3O – Isobatzelline C, 361 C11H10N2O2 – Damirone B, 332 – Cribrostatin 1, 441 C11H10N2O2S – Pulicatin E, 142 C11H10N2O3 – 7-Amino-7-demethoxymimosamycin, 439 C11H10N2O3S – Perfragilin A, 453 C11H10N3O1+ – Makaluvamine B, 364 C11H11Br2N5O2 – Phakellin, 563 C11H11NO2S – Pulicatin C, 140 C11H12N3O1+ – Makaluvamine A, 363 – Makaluvamine C, 365

389

C11H13NO2S – Pulicatin A, 138 – Pulicatin B, 139 C11H15N5O2 – 2-Hydroxy-1ʹ-methylzeatin, 651 C12 C12H8Br2N4 – Meridianin F, 504 C12H8N2O2 – 2-Amino-3H-phenoxazin-3-one, 801 C12H8N2O3 – 2-Amino-6-hydroxy-3H-phenoxazin-3-one, 800 C12H9BrN4 – Meridianin C, 501 – Meridianin D, 502 C12H9BrN4O – Meridianin B, 500 – Meridianin E, 503 C12H9ClN4O4 – Ammosamide D, 307 C12H9N3O – Caerulomycinonitrile, 190 C12H10ClN3OS – Isobatzelline D, 362 C12H10ClN5OS – Ammosamide A, 837 C12H10N2 – Marinoquinoline A, 313 C12H10N2O2 – 9-De-O-methylaaptamine, 461 C12H10N4 – Meridianin G, 505 C12H10N4O – Meridianin A, 499 C12H10N4O2 – Lumichrome, 667 C12H11NO3 – 7-Methoxy-1,6-dimethyl-5,8isoquinolinedione, 450 C12H11NO3S2 – Perfragilin B, 454 C12H11NO4 – Mimosamycin, 452 – Renierol, 455 C12H11N3O2 – Caerulomycin A, 181 – Caerulomycinamide, 182

390

Index 2 Compound Molecular Formula Index

C12H12ClN3OS – Isobatzelline A, 359 C12H12N2O2 – Caerulomycin F, 184 C12H12N2O4 – 4-Aminomimosamycin, 440 C12H13Br2N5O – N1-Methyldibromoisophakellin, 956 C12H13N3OS – Isobatzelline B, 360 C12H14N3O1+ – Makaluvamine H, 370 C12H15NO3 – Helquinoline, 310 C12H18N2O2 – Demethyloxyaaptamine, 462 C12H20N2O – Aflatoxin, 513 C12H20N2O2 – New Aspergillic acid, 531 C12H20N2O3 – (11S)-Hydroxyl aspergillic acid, 525 C13 C13H11BrN2O4 – Agelongine, 177 C13H11NO5 – O-Demethylrenierol acetate, 446 C13H11N5O5 – Desmethylphidolopin, 648 C13H12N2O2 – Caerulomycin K, 189 – Aaptamine, 460 – Isoaaptamine, 463 – Aaptosine, 836 C13H12N4OS – Dendrodoine, 160 C13H13NO4 – Cribrostatin 2, 442 C13H13N3O2 – Caerulomycin J, 188 C13H13N3O3 – Caerulomycin C, 183 – Caerulomycin I, 187 C13H14N2O3 – Caerulomycin G, 185

C13H16BrN3O4 – N1-Methylmanzacidin C, 506 C13H16Cl6N2OS – Dysideathiazole, 129 C13H17Cl5N2OS – 10-Dechlorodysideathiazole, 122 C13H18N2O6 – Bengazole Z, 14 C13H28N2 – Haliclorensin, 831 C14 C14H9NO4 – Caboxamycin, 28 C14H10N2O3 – Penicinolone, 317 C14H11N3O2 – 6-(Hydroxymethyl)-1-phenazinecarboxamide, 576 C14H11N7O – Variolin B, 883 C14H12N2O2 – 1,6-Phenazinedimethanol, 585 C14H12N4O2 – Essramycin, 175 C14H13N5O5 – Phidolopin, 666 C14H14N2O2 – N4-Methylaaptamine, 464 C14H14N2O4 – Venezueline B, 977 C14H17Br2N5O3 – Clavatadine C, 86 C14H17NO – 2-n-Pentyl-4(1H)-quinolinol, 319 C14H18BrN5O3 – Clavatadine E, 88 C14H18Br3N2O1+ – Convolutamine J, 487 C14H18ClNO3 – Salinosporamide C, 870 C14H18Cl6N2OS – N-Methyldysideathiazole, 135 C14H19Cl5N2OS – 10-Dechloro-N-methyldysideathiazole, 123 C14H20Cl4N2OS – 9,10-Didechloro-N-methyldysideathiazole, 126

Index 2 Compound Molecular Formula Index

C15 C15H8BrN3O – Pantherinine, 422 C15H8N4O2 – Granulatimide, 938 – Isogranulatimide, 951 C15H10N2O3 – Penipanoid C, 477 C15H10N2O5 – Carboxyexfoliazone, 802 C15H11NO3 – Viridicatol, 324 – 4-Hydroxy-1-(3-hydroxyphenyl)-3(2H)isoquinolinone, 449 C15H12N2O2 – Deoxy-penipanoid C, 493 C15H12N2O4 – Griseoluteic acid, 575 – Exfoliazone, 805 – Deoxynyboquinone, 849 C15H12N2O5 – Chandrananimycin D, 804 C15H13N7O2 – Variolin A, 882 C15H14N2O3 – Cribrostatin 6, 445 C15H14N4O2 – Dermacozine A, 566 C15H15Br2ClN4O3 – Synoxazolidinone C, 27 C15H15NO – Navenone A, 231 C15H16Br2N4O4 – Aerophobin 1, 74 C15H16N4O4S – Anguibactin, 115 C15H17Br2N5O4 – Purealidin J, 106 C15H17Br2N5O5 – Purealidin K, 107 C15H17N7O – N3′-Methyltetrahydrovariolin B, 858 C15H18N2O – Usabamycin C, 881 C15H18N2O2 – Usabamycin B, 880 C15H18N2O6 – N-1-β-D-Ribofuranosyldamirone C, 380

391

C15H19Br2N5O3 – Clavatadine D, 87 C15H21Br2N5O4 – Purealidin L, 108 C15H21NO7 – Sesbanimide A, 289 C15H21N3O5 – N-1-β-D-Ribofuranosylmakaluvamine I, 381 C15H21N5O7S – Cylindrospermopsin, 848 C15H23N3O5 – Kasarin, 528 C15H27N – Halochonadin F, 693 C16 C16H9N2O81+ – 5,6,9,10-Tetracarboxybenzo[b][1,8]naphthyridinium(1+), 878 C16H10Br5N3O2 – Aspidostomide E, 514 C16H11N2O21+ – Styelsamine C, 434 C16H11N3O3 – Shewanelline C, 478 C16H13N3O2 – Penipanoid B, 867 C16H13N3O3 – Penipanoid A, 176 C16H14N2O4 – 5,10-Dihydrophencomycin methyl ester, 573 C16H15NO5 – O-Demethylrenierone, 447 C16H15N3O2S – Bacillamide A, 116 C16H15N3O3 – 3-(4-Morpholinyl)demethyloxyaaptamine, 465 C16H16N2O3 – Pterocellin A, 868 C16H16N2O4 – Cribrostatin 3, 443 C16H17Br2N5O4 – Aplysinamisine I, 78 C16H17N3OS – Kuanoniamine A, 414 C16H18N6O2 – Hyrtioseragamine A, 526

392

Index 2 Compound Molecular Formula Index

C16H19Br2N5O4 – Aerophobin 2, 75 C16H19N3O7Br2 – N-[4-(Methoxycarbonylamino)-2-oxobutyl]7,9-dibromo-10-hydroxy-8-methoxy-1-oxa2-azaspiro[4.5]deca-2,6,8-triene3-carboxylic acid amide, 96 C16H20N2O2 – Usabamycin A, 879 C16H20N2O3S2 – Watasemycin A, 143 – Watasemycin B, 144 C16H22Cl3NO – Reticulidin A, 729 – Reticulidin B, 730 C16H23Br2N5O4 – Aplysinamisine II, 79 C16H23N – (‒)-(1S,5S,8R)-2-Isocyanoclovene, 743 C16H23NO3 – Antibiotic PF 1140, 178 C16H23NS – 10-isothiocyanato-4,6-amorphadiene, 685 C16H24Cl3NO – Axinyssimide A, 708 C16H25N – Halichonadin C, 673 – (–)-10-Isocyano-4-amorphene, 680 – 10-Isocyano-4-cadinene, 681 – (+)-Axisonitrile 3, 689 – (‒)-Axisonitrile 3, 690 – 10-epi-Axisonitrile 3, 691 – 9-Isocyanopupukeanane, 698 – 9-epi-9-Isocyanopupukeanane, 699 – 2-Isocyanopupukeanane, 700 – 3-Isocyanotheonellin, 707 – (‒)-(1S,2R,5S,8R)-2-Isocyanoclovane, 742 – 2-Isocyanotrachyopsane, 744 C16H25NO – (1S*,4S*,7R*,10S*)-10-Isocyano-5-cadinen4-ol, 682 – 10-Isocyano-5-cadinen-4-ol, 683 – 10-Isocyano-5-cadinen-4-ol, 684 C16H25NOS – Axiplyn C, 677 – 10-Isothiocyanatoamorph-5-en-4-ol, 688 C16H25NO3S – Axiplyn D, 678 – Axiplyn E, 679

C16H25NS – (‒)-Cavernothiocyanate, 670 – 7-Isothiocyanato-11-oppositene, 671 – 4-Isothiocyanato-7α-eudesm-11-ene, 674 – 4-Isothiocyanato-7β-eudesm-11-ene, 675 – 11-Isothiocyano-7βH-eudesm-5-ene, 676 – (–)-10-Isothiocyanato-4-amorphene, 686 – 4-Isothiocyanato-9-amorphene, 687 – (+)-Axisothiocyanate 3, 692 – (1R,4S,5S,6R,7S,10R)-(+)-Isothiocyanatoalloaromadendrane, 694 – epi-Polasin B, 695 – (+)-epi-Polasin A, 697 – (–)-9-Isothiocyanatopupukaenane, 701 – 9-Isothiocyanatopupukeanane, 702 – 2-Thiocyanatoneopupukaenane, 703 – 2-Thiocyanatoneopupukeanane, 704 – 9-Thiocyanatopupukeanane, 705 – 9-epi-Thiocyanatopupukeanane, 706 C16H26Cl3NO2 – Axinyssimide B, 709 – Axinyssimide C, 710 C16H27NO – 4-Formamidoeudesm-7-ene, 672 C16H36N4O4P2S2 – O,O,O′,O′-Tetrapropyl 2,2′-(1,2-dimethyl-1,2ethanediylidene)bis(phosphorohydrazidothioate), 826 C17 C17H9N3O – Sebastianine A, 424 C17H10N2O – Arnoamine A, 389 C17H12N2O3 – Botryllazine B, 515 C17H12N2O4 – Chaetominedione, 847 C17H13N3O3 – Circumdatin F, 908 – Circumdatin L, 909 C17H13N7 – Aplidiopsamine A, 838 C17H15BrN2O – 2-Bromo-5-(2-methyl-2-butylene) phenazinone, 565 C17H15N3O5 – Pelagiomicin C, 580

Index 2 Compound Molecular Formula Index

C17H16N2O3 – Chandrananimycin C, 803 C17H16N3O1+ – Styelsamine D, 435 C17H16N3O21+ – Veiutamine, 385 – Styelsamine A, 432 C17H17NO5 – Renierone, 456 C17H18N2O4 – Cribrostatin 5, 444 C17H18N2O6S – Benzoxacystol, 797 C17H21N3O5 – Oxepinamide A, 866 C17H22Cl6N2O2S – Demethylisodysidenin, 125 C17H23Br2N3O6 – Subereamolline A, 113 C17H23Cl6N3O2S – Dysidenin, 130 – Isodysidenin, 132 – Pseudodysidenin, 137 C17H23NO – Haminol 1, 215 – Haminol 5, 219 – Haminol A, 221 C17H25NO – Haminol 3, 217 C17H28N2O – CPB48-974-8, 193 C17H28N2O2 – Untenine B, 264 C18 C18H8BrN3O – 2-Bromoleptoclinidinone, 395 C18H9NO8 – Ningalin A, 959 C18H9NO11S – Baculiferin O, 904 C18H9N3O – Ascididemin, 393 C18H9N3O2 – Cystodamine, 397 – 9-Hydroxyisoascididemnin, 413 – Meridine, 419 C18H10BrN3O2S – (−)-(6S,8R)-Discorhabdin Q, 347

C18H10N4O – 9-Aminoisoascididemnin, 387 C18H11N3 – 12-Deoxyascididemin, 405 C18H11N3O2 – 8,9-Dihydro-11-hydroxyascididemin, 408 – Labuanine A, 418 C18H12BrN3O2S – Discorhabdin B, 338 – Prianosin B, 379 C18H12Br3N3O2 – 14-Bromo-7,8-didehydro-3dihydrodiscorhabdin C, 328 – 14-Bromodiscorhabdin C, 331 C18H12N2O – Arnoamine B, 390 C18H12N4O – Ecionine A, 410 – Cystodimine A, 919 C18H12N4O2 – Ecionine B, 411 – Cystodimine B, 920 C18H13Br2N3O2 – 7,8-Didehydro-3-dihydrodiscorhabdin C, 334 – Discorhabdin C, 339 C18H13N3O2 – Tsitsikammamine A, 383 C18H13N3O2S – (+)-Discorhabdin I, 343 C18H13N3O3S – Discorhabdin R, 348 C18H14BrN3O2 – Discorhabdin E, 341 C18H14BrN3O2S – 3-Dihydrodiscorhabdin B, 335 – Discorhabdin A, 337 C18H14Br3N3O2 – 14-Bromodihydrodiscorhabdin C, 329 C18H14N3O2S1+ – (+)-(2S,6R,8S)-Discorhabdin D, 340 C18H14N3O3S1+ – (–)-Discorhabdin L, 344 C18H14N4S – N-Deacetylkuanoniamine D, 401 C18H15BrN3O21+ – Discorhabdin G‡, 342 C18H15BrN3O2S1+ – Makaluvamine F, 368

393

394

Index 2 Compound Molecular Formula Index

C18H15Br2N3O2 – Dihydrodiscorhabdin C, 336 – Epinardine C, 358 C18H15Br3N3O21+ – 4-Bromodihydrodiscorhabdin C, 330 C18H15N3O3 – Brevianamide M, 845 C18H15N4O2S1+ – 1-Aminodiscorhabdin D, 325 C18H16BrN3O2 – Discorhabdin Y, 355 C18H16N2O5 – Venezueline E, 807 C18H16N3O21+ – Makaluvamine M, 375 C18H17BrN3O21+ – Discorhabdin V, 352 C18H17Br2NO3 – Saldedine A, 457 C18H18N2O5 – Pseudonocardian A, 968 C18H18N3O21+ – Makaluvamine D, 366 C18H18N3O31+ – Epinardine A, 357 C18H18N3O51+ – (−)-Discorhabdin Z, 356 C18H19Br2NO3 – Saldedine B, 458 C18H19NO6 – (–)-N-Formyl-1,2-dihydrorenierone, 448 C18H19N3O7 – Cyanogriside C, 199 C18H20N4O3 – Aurantiomide C, 840 C18H22N2O4 – Terreusinone, 876 C18H22N4O4 – Aurantiomide B, 839 C18H25NO – 2-Nonyl-4-quinolone, 316 C18H25NO2 – 2-Nonyl-4-hydroxyquinoline N-oxide, 315 C18H29NO – Corydendramine A, 274 – Corydendramine B, 275 C18H30N2O – CPB48-974-7, 192

C18H31NO – (–)-Lepadin B, 312 – Amaminol A, 817 – Amaminol B, 818 C18H32N2 – (S)-Niphatesine C, 236 – Theonelladine C, 261 C18H33N2 – Niphatesine D, 237 C18H34N2O – Pseudodistomin A, 283 – Pseudodistomin B, 284 – Pseudodistomin D, 286 – Pseudodistomin E, 287 C19 C19H10N2O2 – Calothrixin B, 906 C19H10N2O3 – Calothrixin A, 905 C19H11N3O2 – Amphimedine, 388 – Neoamphimedine, 420 C19H12N2O4 – 2-Amino-8-benzoyl-6-hydroxy3H-phenoxazin-3-one, 799 C19H12N3O1+ – Deoxyamphimedine, 404 C19H12N4O – N-Methylisocystodamine, 957 C19H13N3O5 – Rigidin, 512 C19H14N2O3 – Pterocellin B, 869 C19H14N3S1+ – Cyclodercitine, 396 C19H14N4O2 – Auranthine, 893 C19H15N3O2 – Tsitsikammamine B, 384 – Cystodytin J, 400 C19H15N3O2Br2 – Discorhabdin P, 346 C19H15N3O2S2 – 1-Thiomethyldiscorhabdin I, 382 C19H16N4O3 – Auranomide A, 480 – Auranomide C, 482

Index 2 Compound Molecular Formula Index

C19H16N4OS – N-Deacetylshermilamine B, 921 C19H16N4S – Dercitamine, 406 C19H17N3O3 – Zyzzyanone B, 886 C19H18N2O3 – Callophycin A, 846 C19H18N3O21+ – Makaluvamine E, 367 – Makaluvamine L, 374 – Styelsamine B, 433 C19H20N2O5 – Pseudonocardian B, 969 C19H20N3O21+ – Makaluvamine J, 372 – Makaluvamine K, 373 C19H21Cl3N2O2S – 4-O-Demethylbarbamide, 124 C19H21N3O7 – Cyanogriside A, 197 C19H22N2O7 – Cyanogriside B, 198 C19H23NO5S – Symbioimine, 875 C19H25NO2 – Haminol 2, 216 – Haminol 6, 220 – Haminol B, 222 – Haminol C, 223 C19H27NO2 – Haminol 4, 218 C19H28N2O2 – Untenine C, 265 C19H30N2 – Niphatesine A, 234 C19H30N2O2 – Untenine A, 263 C19H31NO3 – Lipoxazolidinone A, 21 C19H32N2 – Theonelladine A, 259 C19H32N2O – Ikimine A, 225 – Ikimine B, 226 C19H33NO2 – (4E,S)-Dysidazirine, 829 – (4E,R)-(–)-Dysidazirine, 830

C19H34N2 – Theonelladine D, 262 C19H34N2O – Cribochaline A, 194 – Ikimine C, 227 C19H35NO – Lepadoformine, 292 C19H38N2O4 – Poecillanosine, 825 C19H40N2 – 1,5-Diazacycloheneicosane, 827 C20 C20H14BrN3O2S – Discorhabdin T, 350 C20H14Br2N4O – (S)-Hamacanthin A, 523 – (S)-Hamacanthin B, 524 C20H14N4 – Nemertelline, 232 C20H14N4O – Wakayin, 386 C20H14N4O3 – (14R)-Oxoglyantrypine, 641 – (14S)-Oxoglyantrypine, 642 C20H15BrN4O – (R)-6-Debromohamacanthin B, 516 – (R)-6″-Debromohamacanthin B, 517 C20H16BrN3O2S – Discorhabdin S, 349 – Discorhabdin U, 351 C20H16NO4S – Kuanoniamine D, 417 C20H16N4O – (S)-6ʹ,6″-Didebromohamacanthin A, 519 – (R)-6ʹ,6″-Didebromohamacanthin B, 520 C20H16N4O3 – 3-Hydroxyglyantrypine, 635 C20H17N3O2S – Diplamine, 409 C20H17N3O4 – Zyzzyanone D, 888 C20H17N4O4S1+ – (–)-(1R,2S,6R,8S)-Discorhabdin N, 345 C20H18N3O21+ – Makaluvamine G, 369 C20H18N4O – (3S,5R)-6ʹ,6ʹ’Didebromo-3, 4-dihydrohama- canthin B, 518

395

396

Index 2 Compound Molecular Formula Index

C20H18N4S – Nordercitin, 421 C20H19N3O3 – Zyzzyanone A, 885 C20H19N3O4 – Fumiquinazoline J, 631 C20H19N4O31+ – Auranomide B, 481 C20H20N3O2 – Tsitsikammamine C, 973 C20H21NO4 – Discoipyrrole C, 828 C20H21N3O2S – Tintamine, 436 C20H21N3O5 – Pelagiomicin B, 579 C20H21N3O6 – Pelagiomicin A, 578 C20H22N3O21+ – Makaluvamine P, 377 C20H22N6O4S2 – Nostocyclamide, 169 C20H22N6O4S3 – Nostocyclamide M, 170 C20H23ClN4O7 – JBIR 35, 19 C20H23Cl3N2O2S – Barbamide, 117 C20H23N3O5 – Bioxalomycin β1, 594 C20H24Br2N6O2 – Aphrocallistin, 646 C20H24CuN2O4 – Antibiotic ZZF 51, 179 C20H25N3O3 – Martefragine A, 23 C20H25N3O5 – Bioxalomycin α1, 592 C20H27NO – 2-Undecen-18-yl-4-quinolone, 322 C20H29NO – 2-Undecyl-4-quinolone, 323 C20H29NO5S – Latrunculin B, 149 C20H30N2O – Niphatesine E, 238 C20H31NO5S – Latrunculin C, 150

C20H32N2O – Ikimine D, 228 – Niphatesine H, 241 C20H33NO3 – Lipoxazolidinone B, 22 – Lepadin A, 311 C20H33N3 – Oceanapamine, 712 C20H34N2 – Theonelladine B, 260 C20H34N2O – Niphatesine G, 240 – Pseudodistomin F, 288 C20H34N2S – Fascularine, 291 C20H35NO – Clavepictine B, 294 C20H43N2O – Pseudodistomin C, 285 C21 C21H17BrCl2N4 – Perophoramidine, 423 C21H17N5O2 – Grossularine 2, 940 C21H18N4O2 – Fumiquinazoline F, 627 – Fumiquinazoline G, 628 C21H18N4O2S – Shermilamine B, 427 C21H18N4OS – Kuanoniamine C, 416 C21H19Br3N4O – Dragmacidin, 521 C21H19N3O4 – Zyzzyanone C, 887 C21H20N4O2S – Shermilamine E, 430 C21H20N4OS – Shermilamine D, 429 C21H20N4S – Dercitin, 407 C21H21N3O – Almazole C, 1 C21H21N3O2S – Varamine B, 438 C21H21N5O2 – Penispirolloid A, 318

Index 2 Compound Molecular Formula Index

C21H22N2O7 – Phenazine Alkaloid 1, 581 – Phenazine Alkaloid 2, 582 – Phenazine Alkaloid 3, 583 – Phenazine Alkaloid 4, 584 C21H23Br4N3O5 – Araplysillin 1, 81 C21H23Br4N3O6 – Psammaplysin A, 99 C21H23Br4N3O7 – Psammaplysin B, 100 C21H23Br4N3O9S – 19-Hydroxyaraplysillin N20sulfamate, 93 C21H24N2O4 – Chelonin A, 798 C21H24N2O8 – Pseudonocardian C, 970 C21H25ClN4O7 – JBIR 34, 18 C21H25N3O5 – Bioxalomycin β2, 595 C21H26BrNO2 – Hamigeran D, 943 C21H26N6O4S2 – Dolastatin E, 162 C21H27NO – (–)-Isopuloupone, 229 C21H27NO2 – Ileabethoxazole, 946 C21H27N3O5 – Bioxalomycin α2, 593 C21H29NO3 – Smenospongine, 735 – 5-epi-Smenospongine, 736 C21H31NO5S – Latrunculin D, 151 C21H34N2 – Niphatesine B, 235 C21H36N2O – Cribrochalinamine oxide A, 195 C21H38N2OS – Kalkitoxin, 133 C22 C22H17N3O2 – Arnoamine C, 391 – Arnoamine D, 392

C22H17N3O4 – Dermacozine C, 568 C22H18N4O3 – Dermacozine B, 567 C22H18N4O4 – Isochaetominine A, 636 C22H19N3O2 – Cystodytin A, 398 – Cystodytin B, 399 C22H19N3O3 – Sebastianine B, 425 C22H20Br4N4O9 – Aplysina archeri Alkaloid, 77 C22H21N3O3 – Almazole D, 2 C22H22Br3N3O3 – Maedamine B, 530 C22H23BrN2O – 2-Bromolavanducyanin, 564 C22H23Br4N3O7 – Ceratinamide A, 84 C22H23N3O2S – Varamine A, 437 C22H24N2O – Lavanducyanin, 577 C22H24N2O2 – Geranylphenazinediol, 574 C22H24N2O5 – Streptophenazine E, 590 C22H24N4O2 – Aspeverin, 889 C22H25Br4N3O5 – Purealidin S, 112 C22H25Br4N3O7 – Psammaplysin C, 101 C22H25N3O3 – Fumitremorgin C, 634 C22H26BrN7O – Urochordamine A, 668 – Urochordamine B, 669 C22H26Br4N10O22+ – Nagelamide Z, 168 C22H29NO2 – 7-[(1,2,3,4,4a,7,8,8a-Octahydro-1,2,4a, 5-tetramethyl-1-naphthalenyl)methyl]6-benzoxazolol, 32 C22H29NO3 – Nakijinol B, 31

397

398

Index 2 Compound Molecular Formula Index

C22H31NO2 – 3‘-Methylaminoavarone, 715 – 4ʹ-Methylaminoavarone, 716 C22H31NO5S – Latrunculin A, 148 C22H32N2O3S – Mycothiazole, 136 C22H33NO5S – Latrunculin S, 152 C22H33NOS – Curacin D, 121 C22H33N2O2 – Echinoclathrine A, 207 C22H34N2O – Niphatesine F, 239 C22H36N2O – Niphatyne A, 244 – Niphatyne B, 245 C22H37NO2 – Clavepictine A, 293 C22H41N5O – Phloeodictine A4, 812 – Phloeodictine A5, 813 C23 C23H15N3O4 – Dermacozine F, 571 C23H15N3O5 – Dermacozine G, 572 C23H16N4O3 – Dermacozine E, 570 C23H18N6O – Grossularine 1, 939 C23H19N3O3 – Segoline A, 426 C23H20N4O4 – Isochaetominine B, 637 C23H20N4OS – Dehydrokuanoniamine B, 402 – Dehydrokuanoniamine F, 403 C23H21ClN4O4S2 – Lodopyridone, 134 C23H22N4O4 – Cladoquinazoline, 620 – epi-Cladoquinazoline, 621 C23H22N4OS – Kuanoniamine B, 415 C23H24Br3N3O3 – Maedamine A, 529

C23H25Br4N3O7 – Aplysinamisine III, 80 C23H26N2O5 – Streptophenazine C, 588 – Streptophenazine D, 589 C23H27Br4N3O5 – Purealidin P, 109 – Purealidin Q, 110 C23H29NO3 – Indosespene, 714 C23H29NO4 – Sespenine, 745 C23H31NO5 – Nakijiquinone A, 718 – Smenospongine B, 737 C23H32ClNO3 – Halichlorine, 295 C23H33NO6S – Nakijiquinone R, 728 C23H34N2O4S2 – Agrochelin, 114 C23H35NOS – Curacin A, 118 – Curacin B, 119 – Curacin C, 120 C23H36ClNO4 – Pinnaic acid, 282 C23H38N2O – Cribrochalinamine oxide B, 196 C23H43N5O – Phloeodictine A3, 811 C24 C24H12N4 – Eilatin, 412 C24H14N2O2 – Xylopyridine A, 884 C24H19N3O5 – Dermacozine D, 569 C24H19N5O4 – Cottoquinazoline D, 918 C24H21N3O4 – Canogramide, 907 C24H21N3O6 – Venezueline A, 806 C24H21N5O4 – Fumiquinazoline C, 624 – Fumiquinazoline D, 625

Index 2 Compound Molecular Formula Index

C24H22Br2N6O8 – Oceanapia Quinolone alkaloid, 97 C24H22N4O2S – Shermilamine C, 428 – Shermilamine F, 431 C24H22N4O4 – Aniquinazoline D, 619 – Isochaetominine C, 638 – 14-epi-Isochaetominine C, 639 C24H23N3O7 – Methyl-3,4,5-trimethoxy-2(2-(nicotinamido)benzamido)benzoate, 230 C24H23N5O4 – Fumiquinazoline A, 622 – Fumiquinazoline B, 623 C24H24Br4N4O10 – 12R-Hydroxy-11-oxoaerothionin, 94 C24H24Br4N4O9 – 11-Oxoaerothionin, 98 C24H25BrN4O22+ – Nakijinamine A, 861 C24H26Br4N4O8 – Aerothionin, 76 C24H26Br4N4O9 – 11-Hydroxyaerothionin, 92 C24H26N4O22+ – Nakijinamine B, 862 C24H28N2O5 – Streptophenazine A, 586 – Streptophenazine B, 587 C24H28N2O6 – Streptophenazine H, 591 C24H29NO7 – Didymellamide A, 206 C24H30Br4N3O51+ – Purealidin B, 105 C24H30Br4N3O61+ – Psammaplysin H, 104 C24H32Cl2N2O8S2 – Dolabellin, 127 C24H33NO5 – Smenospongine C, 738 C24H33NO6 – Nakijiquinone C, 720 C24H35NO2 – Petrosaspongiolide L, 249 C24H36N2S – epi-Polasinthiourea B, 696

C24H38N2O7 – Farneside A, 711 C24H45N5O – Phloeodictine A2, 810 C24H47N6O31+ – Norcrambescin B1, 507 – Norcrambescin C1, 508 C25 C25H19NO8 – Ningalin B, 864 C25H20BrN7O2 – Dragmacidin E, 522 C25H21N5O3 – Quinadoline B, 643 C25H23N5O5 – Fumiquinazoline L (Zhou, 2013), 632 C25H25N5O5 – Fumiquinazoline E, 626 C25H26BrN5O11 – Prosurugatoxin, 967 C25H27N5O5 – Monodontamide F, 476 C25H28Br4N4O8 – Homoaerothionin, 91 C25H31NO7 – Thallusin, 258 C25H32N2O2S – Echinoclathrine C, 209 C25H35NO6 – Nakijiquinone D, 721 C25H37NO3 – Nakijiquinone O, 726 – Smenospongorine, 739 – 5-epi-Smenospongorine, 740 C25H37NO4 – Hippolide A, 751 C25H37NO4S – Nakijiquinone I, 724 C25H40N2 – (–)-Haliclonadiamine, 941 – (–)-Papuamine, 966 C25H41ClN2O6S – Tauropinnaic acid, 290 C25H45N6O21+ – Didehydrocrambescin A1, 494 C25H47N5O – Phloeodictine A1, 809

399

400

Index 2 Compound Molecular Formula Index

C25H47N6O21+ – Crambescin A1, 488 – Crambescin A2, 489 C25H48N6O3 – Crambescin B, 490 C25H49N5O – Phloeodictine A7, 815 C25H49N6O31+ – Crambescin B1, 491 – Crambescin C1, 492 C26 C26H17NO10 – Baculiferin N, 844 C26H24N8O3 – Hyrtioseragamine B, 527 C26H25BrN5O4S1+ – Nakijinamine C, 29 C26H25N5O4 – Aniquinazoline A, 470 – Norquinadoline A, 640 – Cottoquinazoline C, 917 C26H27N5O4 – Aniquinazoline B, 471 C26H27N5O5 – Aniquinazoline C, 472 C26H28Br2N7O7 – Tyrokeradine B (2009), 321 C26H33NO5 – Nakijinol B diacetate, 717 C26H35N3O3 – Nakijiquinone G, 722 C26H37NO5 – Nakijiquinone B, 719 C26H38N4O – Malonganenone J, 656 C26H38N4O2 – Malonganenone A, 652 – Malonganenone D, 653 – Malonganenone E, 654 – Malonganenone I, 655 C26H39NO3 – Nakijiquinone N, 725 – Smenospongiarine, 731 – 5-epi-Smenospongiarine, 732 C26H40N2 – Keramaphidin B, 952 C26H40N2O – Ingenamine, 949

C26H40N4O3 – Nakijiquinone H, 723 C26H40N5O1+ – (–)-Ageloxime D, 645 C26H41N5O – Axistatin 1, 483 – Axistatin 2, 484 C26H42N2 – Halicyclamine B, 278 C26H42N2O8 – Bengazole C, 7 C26H49N5O – Phloeodictine A, 808 C26H49N6O21+ – Homocrambescin A2, 495 C26H51N5O – Phloeodictine A6, 814 C26H51N6O31+ – Homocrambescin B1, 496 – Homocrambescin C1, 497 C27 C27H19N5O – Biemnadin, 394 C27H23NO4 – Discoipyrrole B, 851 C27H23NO5 – Discoipyrrole A, 850 C27H24N2O5 – Aspernigrin B, 180 C27H24N3O31+ – Thorectandramine, 972 C27H25Br4N3O8 – Psammaplysin E, 103 C27H25Br4NO6 – Theoneberine, 459 C27H27Br4N3O9 – 19-Hydroxypsammaplysin E, 95 C27H27N5O4 – Fumiquinazoline H, 629 C27H29NO6 – Xylogranatopyridine A, 268 C27H29N5O4 – Fumiquinazoline I, 630 C27H30N2O9 – Jorumycin, 605 – Xestomycin, 618 C27H30N4O2 – Communesin E, 915

Index 2 Compound Molecular Formula Index

C27H32N2O8 – Lobatamide A, 821 – Lobatamide B, 822 – Lobatamide C, 823 C27H32N2O9 – Lobatamide D, 824 C27H38N2O3S – Echinoclathrine B, 208 C27H40N4O3 – Nuttingine A, 661 – Nuttingine B, 662 C27H41NO5 – Kimbasine B, 754 C27H41NO7S – Coscinolactam A, 746 – Coscinolactam B, 747 C27H42N4O2 – Nuttingine C, 663 – Nuttingine D, 664 – Nuttingine E, 665 C27H42N6O6 – Cycloxazoline, 33 C27H44N2O7 – Bengazole C4, 8 – Bengazole C6, 9 C27H44N2O8 – Bengazole A, 5 – Bengazole D, 10 C27H53N8OS3+ – Phloeodictyne B, 816 C28 C28H26N4O6 – Suberitine A, 466 – Suberitine C, 468 C28H28N4O6 – Deoxynortryptoquivaline, 474 C28H32N4O – Communesin F, 916 C28H32N4O2 – Communesin A, 911 C28H37NO3 – Asporyzin A, 890 – Asporyzin B, 891 C28H39NO2 – Asporyzin C, 892

C28H39N3O4 – Citrinadin B, 910 C28H44N2O – Dihydroingenamine D, 934 C28H46N2O8 – Bengazole B, 6 – Bengazole E, 11 C28H50N2O2 – Araguspongine B, 299 – (+)-Araguspongine D, 300 – Araguspongine E, 301 C28H50N2O3 – Xestospongin D, 306 C29 C29H30N4O6 – Deoxytryptoquivaline, 475 C29H30N4O7 – Tryptoquivaline, 479 C29H31N5O5 – Fumiquinazoline S, 633 C29H34BrN5O22+ – Nakijinamine F, 863 C29H35N3O9S – Ecteinascidin 583, 597 C29H37NO3 – Nakijiquinone P, 727 – Smenospongidine, 733 – 5-epi-Smenospongidine, 734 C29H37NO6 – Norzoanthaminone, 964 C29H39NO5 – Norzoanthamine, 962 C29H41NO5 – epi-Norzoanthamine, 963 C29H41N7O4S4 – Mayotamide B, 155 C29H42N2O6 – (–)-Hennoxazole A, 16 C29H45NO5 – Kimbasine A, 753 C29H46NO10P – Enigmazole A, 15 C29H46N2 – Plakinamine A, 787 C29H47N5O – Axistatin 3, 485

401

402

Index 2 Compound Molecular Formula Index

C29H48N2 – 24,25-Dihydroplakinamine A, 781 C29H48N2O8 – Bengazole F, 12 – Bengazole G, 13 C29H52N2O3 – Xestospongin B, 305 C30 C30H28BrN7O22+ – Nakijinamine E, 30 C30H30N2O10 – Cribrostatin 4, 596 C30H31N3O8 – Renieramycin S, 617 C30H32N2O10 – Renieramycin C, 608 C30H32N2O10S – Ecteinascidin 594, 598 C30H32N2O9 – Renieramycin G, 610 C30H33NO7 – Pileotin B, 250 C30H34BrN5O15 – Neosurugatoxin, 958 C30H34N2O – Cortistatin J, 760 C30H34N2O4 – Cortistatin C, 758 C30H34N2O5 – Cortistatin D, 759 C30H34N2O9 – Renieramycin A, 606 C30H36N2O3 – Cortistatin A, 756 C30H36N2O4 – Cortistatin B, 757 C30H43N7O4S4 – Mayotamide A, 154 C30H44N2 – Ingamine B, 948 – Madangamine A, 953 C30H44N22+ – Njaoaminium A, 246 C30H44N2O – Ingamine A, 947 C30H44N2O2 – 22-Hydroxyingamine A, 944

C30H44N2O6 – Hennoxazole B, 17 C30H44N3O6S – 19-Oxofasciospongine A, 755 C30H45NO8 – Glucopiericidin C, 210 C30H47N3O5S – Fasciospongine A, 748 – Fasciospongine B, 749 C30H50N2 – Plakinamine J, 794 C30H50N2O2 – Petrosine, 302 – Petrosine A, 303 – Petrosine B, 304 C30H51NO5S – Irregularasulfate, 752 C30H52N2 – Neopetrosiamine A, 280 – N30-Methyl-23ξ,24ξ,25,30tetrahydroplakinamine A, 786 C30H52N2O2 – Aragupetrosine A, 298 C30H52N4O5S – Fasciospongine C, 750 C30H54N2 – Haliclamine C, 211 C31 C31H30Br6N4O11 – Fistularin 3, 89 – 11-epi-Fistularin 3, 90 C31H32N2O10 – Renieramycin I, 611 C31H33N3O8 – Renieramycin M, 612 C31H33N3O9 – Renieramycin O, 614 – Renieramycin Q, 615 C31H34N4O2 – Communesin C, 913 C31H35NO8 – Divergolide C, 936 – Divergolide D, 937 C31H35N3O9 – Renieramycin N, 613 C31H37NO7 – Divergolide B, 853

Index 2 Compound Molecular Formula Index

C31H39NO8 – Divergolide A, 935 C31H43N3O4S – (–)-Pateamine A, 156 C31H44BrNO9 – Leiodolide B, 62 C31H45NO9 – Leiodolide A, 61 C31H46N22+ – Njaoaminium C, 248 C31H46N2O9 – Neopeltolide, 24 C31H48N2O – Plakinamine F, 792 C31H48N2O2 – Lokysterolamine B, 784 C31H50N2 – Plakinamine B, 788 – Plakinamine I, 793 C31H50N2O – Isosaraine 1, 296 – Saraine 1, 297 – Lokysterolamine A, 783 C31H50N2O2 – Plakinamine E, 791 C31H56O2 – Haliclamine D, 212 C32 C32H21NO12 – Baculiferin L, 902 C32H21NO15S – Baculiferin M, 903 C32H23NO9 – Baculiferin K, 843 C32H23NO10 – Ningalin C, 865 C32H23NO12S – Baculiferin I, 841 – Baculiferin J, 842 C32H27NO4 – Haouamine A, 856 C32H27NO5 – Haouamine B, 857 C32H34N4O3 – Communesin D, 914 C32H35N3O9 – Renieramycin R, 616

403

C32H36Br4N10O8 – Archerine, 83 C32H36N2O10 – Renieramycin D, 609 C32H36N4O2 – Communesin B, 912 C32H38N2O9 – Renieramycin B, 607 C32H38N4O7 – Ariakemicin A, 3 – Ariakemicin B, 4 C32H42N2O6 – 22-O-(N-Me-L-valyl)-21-epiaflaquinolone B, 314 C32H44N2O2 – Drimentine G, 713 C32H45NO4 – Gymnodimine, 854 C32H45NO5 – Gymnodimine B, 855 C32H48N22+ – Haliclona 3-Alkylpyridinium dimer, 213 – Njaoaminium B, 247 C32H48N2O4 – Haliclonine A, 942 C32H49N3O5S – Alotamide A, 153 C32H50N2O – N3-Methyl-4-oxo-3-epi-plakinamine B, 785 – Ingenamine G, 950 – Densanin B, 923 C32H52N2O2 – Plakinamine K, 795 C32H54N2O2 – Dihydroplakinamine K, 782 C32H56N2 – Haliclonacyclamine A, 276 – Haliclonacyclamine B, 277 C33 C33H44N2O7S – Erythrazole B, 145 C33H49N2O3 – Densanin A, 922 C33H52N2O2 – 4-Acetoxyplakinamine B, 780 C33H54N2O2 – Plakinamine C, 789 – Plakinamine D, 790

404

Index 2 Compound Molecular Formula Index

C33H58N2O – Plakinamine M, 796 C33H60N2O – 22-Hydroxyhaliclonacyclamine B, 279 C34 C34H23BrN2O6 – Dictyodendrine H, 931 C34H23IN2O6 – Dictyodendrine I, 932 C34H24N2O12S2 – Dictyodendrine D, 927 C34H24N2O6 – Dictyodendrine F, 929 C34H24N2O8 – Dictyodendrine J, 933 C34H24N2O9S – Dictyodendrine C, 926 C34H27N3O7 – Variecolortide B, 975 C34H30N8O6S2 – Urukthapelstatin A, 174 C34H40N6O6S4 – Tetroazolemycin A, 558 – Tetroazolemycin B, 559 C34H56N22+ – Cyclostellettamine A, 200 C35 C35H26N2O6 – Dictyodendrine G, 930 C35H29N3O7 – Variecolortide C, 976 C35H32N8O7S – Mechercharstatin A, 167 C35H40N4O4 – Halytulin, 309 C35H43N7O5S2 – Lissoclinamide 1, 163 C35H46N4O4S – Dolastatin 18, 128 C35H48N31+ – Niphatoxin A, 242 C35H58N22+ – Cyclostellettamine B, 201 C35H58N4O7S3 – Hoiamide D, 131

C36 C36H20N2O4 – Scytonemin, 874 C36H22Br2N6O4S2 – (S,S)-Discorhabdin W, 353 – (R,R)-Discorhabdin W, 354 C36H27Cl3N6O4 – Diazonamide D, 36 C36H28Cl2N6O4 – Diazonamide E, 37 C36H50N31+ – Niphatoxin B, 243 C36H51Br4N3O6 – Araplysillin 2, 82 C36H51Br4N3O7 – Ceratinamide B, 85 C36H51Br4N3O8 – Psammaplysin D, 102 C36H57N3O – Pyrinodemin D, 255 C36H60N22+ – Cyclostellettamine C, 202 – Cyclostellettamine D, 203 C36H69NO11S2 – Penasulfate A, 281 C37 C37H57N3O – Pyrinodemin C, 254 C37H59N3O – Pyrinodemin B, 253 C37H62N22+ – Cyclostellettamine E, 204 C38 C38H34N2O7 – Discoipyrrole D, 852 C38H41N3O11S – Ecteinascidin 729, 599 C38H41N7O5S2 – Lissoclinamide 5, 165 C38H43N7O5S2 – Lissoclinamide 4, 164 – Lissoclinamide 6, 166 C38H46N2O4 – Trikendiol, 741 C38H56N2O10 – Leucascandrolide A, 20

Index 2 Compound Molecular Formula Index

C38H59N3O – Pyrinodemin A, 252 C38H61N5O8 – Nocardichelin B, 26 C38H64N22+ – Cyclostellettamine F, 205 C38H66N2O19S3 – Cyclodidemniserinol, 819

C41 C41H30N2O10S – Dictyodendrine B, 925 C41H39N2O9S – Dictyodendrine E, 928 C41H67N2O16S3 – Schulzeine B, 872 – Schulzeine C, 873

C39 C39H35N3O7 – Variecolortide A, 974 C39H43N3O10S – Ecteinascidin 745, 602 C39H43N3O11S – Ecteinascidin 743, 601 C39H43N3O12S – Ecteinascidin 759B, 603 C39H66N3O21+ – Viscosaline, 266

C42 C42H72N2O16S3 – Schulzeine A, 871

C40 C40H27NO11 – Purpurone, 971 C40H27NO12 – Ningalin D, 960 – Ningalin G, 961 C40H27NO14S – Baculiferin A, 894 – Baculiferin B, 895 C40H27NO17S2 – Baculiferin C, 896 – Baculiferin D, 897 – Baculiferin E, 898 – Baculiferin F, 899 C40H27NO20S3 – Baculiferin G, 900 – Baculiferin H, 901 C40H34Cl2N6O6 – Diazonamide A, 34 C40H35Cl2N7O5 – Diazonamide C, 35 C40H42N4O10S – Ecteinascidin 770, 604 C40H42N4O9S – Ecteinascidin 736, 600 C40H65N5O8 – Nocardichelin A, 25

405

C43 C43H30N2O12S – 4-Hydroxy-1ʹ,3,4ʹ-tri(4-hydroxyphenyl)-3ʹ[2-(4-hydroxyphenyl)ethyl]-7ʹ-(sulfooxy) spiro[furan-2(5H),2ʹ(3ʹH)-pyrrolo[2,3-c] carbazole]- 5,5ʹ(6ʹH)-dione, 945 C43H32N2O11S – 37-(Methoxycarbonyl)dictyodendrine E, 954 C43H34N2O11S – Dictyodendrine A, 924 C43H60N4O13 – Halishigamide B, 41 C44 C44H60N4O12 – Halichondramide, 39 – Isohalichondramide, 47 C44H60N4O13 – Jaspisamide B, 49 C44H62N4O12 – Dihydrohalichondramide, 38 C44H62N4O13 – Jaspisamide A, 48 C44H63N5O12 – Halishigamide A, 40 C44H64N4O14 – Halishigamide C, 42 – Halishigamide D, 43 C45 C45H60N4O12 – Jaspisamide C, 50 C45H62N4O13 – 32-Hydroxymycalolide A, 44

406

Index 2 Compound Molecular Formula Index

C45H64N4O12 – Kabiramide L, 60 – 33-Methyldihydrohalichondramide, 63 C45H81N6O51+ – Monanchomycalin B, 860 C46 C46H62N4O13 – Mycalolide E, 67 C46H64N4O13 – Ulapualide A, 72 C46H65N5O13 – Kabiramide J, 58 C46H66N4O12 – Kabiramide K, 59 C46H69NO13 – Azaspiracid 4, 271 – Azaspiracid 5, 272 C47 C47H64N4O14 – Mycalolide A, 64 C47H66N4O14 – 30-Hydroxymycalolide A, 45 C47H67N5O13 – Kabiramide G, 57 C47H69N5O14 – Kabiramide B, 52 C47H70N4O13 – Kabiramide D, 55 C47H71NO12 – Azaspiracid 1, 269 – Azaspiracid 6, 273 C47H85N6O51+ – Monanchomycalin A, 859 C48 C48H71N5O14 – Kabiramide C, 53 C48H71N5O15 – Kabiramide A, 51 C48H72N33+ – Haliclona 3-Alkylpyridinium trimer, 214 C48H73NO12 – Azaspiracid 2, 270

C49 C49H72N4O14 – Kabiramide E, 56 C49H77NO11S – Patellazole A, 157 C49H77NO12S – Patellazole B, 158 C49H77NO13S – Patellazole C, 159 C50 C50H72N4O17 – Mycalolide D, 66 C50H73N5O15 – Kabiramide C acetate, 54 C51 C51H72N4O16 – Mycalolide C, 65 C51H72N4O17 – 38-Hydroxymycalolide B, 46 C51H74N4O16 – Ulapualide B, 73 C52 C52H54N6O7 – Waikialoid A, 978 C52H54N6O9 – Waikialoid B, 979 C53 C53H70N2O10 – Cephalostatin 6, 766 C53H71BrN2O13 – Phorboxazole A, 68 – Phorboxazole B, 69 C54 C54H72N2O10 – Cephalostatin 5, 765 C54H72N2O12 – Cephalostatin 14, 774 C54H74N2O10 – Cephalostatin 1, 761 – Cephalostatin 16, 776 – Cephalostatin 17, 777

Index 2 Compound Molecular Formula Index

C54H74N2O11 – Cephalostatin 2, 762 C54H74N2O12 – Cephalostatin 4, 764 C54H76N2O8 – Ritterazine N, 545 – Ritterazine O, 546 – Ritterazine T, 551 – Ritterazine W, 554 – Ritterazine X, 555 C54H76N2O9 – Ritterazine G, 538 – Ritterazine H, 539 – Ritterazine L, 543 – Ritterazine M, 544 – Ritterazine U, 552 – Ritterazine V, 553 C54H76N2O10 – Ritterazine A, 532 – Ritterazine D, 535 – Ritterazine I, 540 – Ritterazine K, 542 C54H76N2O11 – Ritterazine J, 541 – Cephalostatin 7, 767 – Cephalostatin 9, 769 C54H76N2O12 – Cephalostatin 12, 772 C54H76N2O13 – Cephalostatin 13, 773 C54H78N2O7 – Ritterazine P, 547 – Ritterazine Q, 548 – Ritterazine Y, 556 C54H78N2O9 – Ritterazine B, 533 – Ritterazine C, 534 – Ritterazine F, 537 C54H80N2O6 – Ritterazine R, 549 – Ritterazine S, 550

C54H90N33+ – Viscosamine, 267 C55 C55H74N2O12 – Cephalostatin 15, 775 C55H76N2O11 – Cephalostatin 3, 763 – Cephalostatin 18, 778 – Cephalostatin 19, 779 C55H76N2O12 – Cephalostatin 10, 770 – Cephalostatin 11, 771 C55H78N2O9 – Ritterazine Z, 557 C55H78N2O10 – Ritterazine E, 536 – Cephalostatin 8, 768 C57 C57H81N7O20S – Thiomycalolide A, 70 C58 C58H62N2O10 – Oxazinin A, 965 C62 C62H91N7O23S – Thiomycalolide B, 71 C77 C77H136N4O22S2 – Theonezolide B, 172 C79 C79H140N4O22S2 – Theonezolide A, 171 C81 C81H144N4O22S2 – Theonezolide C, 173

407

Index 3 Compound Organism Source Index This index lists in alphabetical order all 471 marine organism in Latin names in HAMNP Volume 4, 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 18 of this index, one will know that the Haliclona sp. is a sponge. A Aaptos aaptos 460, 461, 462, 463, 464, 836. Aaptos sp. 465. Aaptos suberitoides 466, 467, 468, 469. Acanthella acuta 680, 689. Acanthella carteri 561, 562. Acanthella cavernosa 670, 671, 674, 674, 676, 688, 689, 692, 692, 694, 695, 695. Acanthella cf. cavernosa 670, 671, 689, 692. Acanthella klethra 674, 675, 676, 689, 692. Acanthella pulcherrima 676. Acanthella sp. 675, 676, 689, 694. Acanthus ilicifolius 317. Acremonium sp. 629, 630, 866. Actinoalloteichus cyanogriseus 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 197, 198, 199, 907. Actinomadura sp. M045 803. Actinotrichia fragilis 910. Agelas axifera 483, 484, 485. Agelas clathrodes 177. Agelas conifera 177. Agelas dispar 177, 251, 561, 562. Agelas longissima 177, 561, 562, 649. Agelas nakamurai 645. Agelas oroides 89, 90. Agelas sp. 168, 563. Agrobacterium aurantiacum N-81106 498. Agrobacterium sp. 114. Agrobacterium sp. PH-130 289. Aiolochroia crassa 75, 108. Alternaria brassicae 651. Amathia tortuosa 487. Amphicarpa meridian 419. Amphimedon sp. 192, 193, 252, 253, 254, 255, 388, 833, 952. Amphimedon viridis 650. Amphiscolops sp. 875. Anthosigmella cf. raromicrosclera 191. Anvhinoe paupertas 835.

Aphiporus angulatus 232. Aphrocallistes beatrix 646. Aplidiopsis confluata 838. Aplidium haouarianum 856, 857. Aplidium lobatum 821, 822, 823, 824. Aplidium meridianum 499, 500, 501, 502, 503, 504, 505. Aplidium pantherinum 422. Aplidium sp. 821, 822, 823, 824. Aplysina aerophoba 76, 91. Aplysina archeri 77, 83, 89. Aplysina caissara 92. Aplysina cauliformis 78, 79, 80, 96. Aplysina fistularis 76, 89. Aplysina fistularis f. fulva 94. Aplysina lacunosa 92, 98. Aplysina thiona 76. Aplysinella sp. 99, 102, 103. Aplysinella strongylata 95. Aspergillus fumigatus 250, 622, 623, 624, 624, 625, 625, 626, 627, 628, 631. Aspergillus nidulans MA-143 470, 471, 472, 619. Aspergillus niger 180. Aspergillus oryzae 890, 891, 892. Aspergillus sp. 632, 633, 636, 637, 638, 639, 978, 979. Aspergillus sp. 16-02-1 513, 525, 531. Aspergillus sp. XS-20090B15 314. Aspergillus sydowi PFW1-13 634. Aspergillus terreus MFA460 876. Aspergillus terreus PT06-2 230. Aspergillus variecolor B-17 974, 975, 976. Aspergillus versicolor 324, 845, 845. Aspergillus versicolor dl-29 889. Aspergillus versicolor MST-MF495 and LCJ-5-4 917, 918. Aspergillus westerdijkiae DFFSCS013 908, 909. Aspidostoma giganteum 514. Asterias amurensis 658. Asterias rubens 658.

Index 3 Compound Organism Source Index

Axinella brevistyla 506. Axinella cannabina 676, 689, 692, 695. Axinella damicornis 177, 180. Axinella fenestratus 688. Axinella sp. 697. Axinella verrucosa 913, 914. Axinyssa aculeata 705, 706. Axinyssa ambrosia 676. Axinyssa aplysinoides 678, 679, 689, 695, 697, 703, 704. Axinyssa fenestratus 685, 687. Axinyssa isabela 674. Axinyssa sp. 672, 677, 680, 695, 701, 708, 709, 710. Axinyssa sp. nov. 702. B Babylonia japonica 958, 967. Bacillus endophyticus SP31 116. Bacillus hunanensis 828, 850, 851, 852. Bacillus sp. SY-1 116. Batzella sp. 326, 327, 346, 349, 350, 351, 359, 360, 361, 362. Biemna fortis 387, 394, 413, 418. Biemna sp. 394, 408, 955, 957. Botrylloides sp. 668, 669. Botryllus leachi 515. Brevibacterium sp. KMD 003 576, 585. Bruguiera gymnorrhiza 853, 935, 936, 937. Bulla gouldiana 229. Bunodosoma caissarum 647. C Cacospongia mycofijiensis 136. Cadlina luteomarginata 675, 676. Callophycus oppositifolius 846. Callyspongia sp. 263, 264, 265, 576, 585. Calothrix sp. 905, 906. Castaniopsis fissa 179. Cephalodiscus gilchristi 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779. Chaetomium sp. 847. Chelonaplysilla sp. 798. Chelynotus semperi 414, 415, 416, 416, 417, 427, 427. Chromodoris elisabethina 148. Chromodoris hamiltoni 148, 149. Chromodoris lochi 136, 148.

409

Cinachyrella enigmatica 15. Ciona savignyi 668, 669. Cladiella sp. 917, 918. Cladosporium sp. PJX-41 474, 475, 479, 620, 621, 635, 640, 641, 642, 643. Clavelina lepadiformis 212, 292, 311, 312. Clavelina picta 293, 294. Clavelina sp. 386. Codium fragile 889. Conus pulicarius 138, 139, 140, 141, 142. Corticium niger 782, 793, 794, 795. Corticium simplex 756, 757, 758, 759, 760. Corticium sp. 419, 780, 781, 783, 784, 785, 786, 789, 790, 791, 792, 796. Corydendrium parasiticum 274, 275. Corynebacterium sp. 958. Coscinoderma mathewsi 746, 747. Crambe crambe 488, 489, 490, 491, 492, 494, 495, 496, 497, 507, 508. Cribochalina sp. 194. Cribrochalina sp. 195, 196, 441, 442, 443, 444, 445, 447, 456, 596. Cylindrospermopsis raciborskii 848. Cystodytes dellechiajei 393, 397, 398, 399, 424, 425, 919, 920, 921. Cystodytes sp. 389, 390, 398, 400, 402, 412, 416, 417, 427, 428. Cystodytes violatinctus 391, 392, 403, 429, 430, 431, 436. Cytophaga sp. YM2-23 258. D Dactylospongia elegans 31, 717, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740. Damiria sp. 332. Dendrilla membranosa 320. Dendrodoa grossularia 160, 939, 940. Dercitus sp. 396, 407. Dermacoccus abyssi sp. nov. 566, 567, 568, 569, 570, 571, 572. Diaperoecia californica 648. Diazona chinensis 34. Diazona sp. 35, 36, 37. Dictyodendrilla sp. 945, 954. Dictyodendrilla verongiformis 924, 925, 926, 927, 928. Didemnum conchyliatum 951. Didemnum granulatum 938, 951. Didemnum guttatum 819.

410

Index 3 Compound Organism Source Index

Didemnum molle 154, 155. Didemnum rubeum 393. Didemnum sp. 393, 864, 865, 959, 960, 961. Diplosoma sp. 409. Dolabella auricularia 127, 128, 162. Dragmacidon sp. 521. Druinella purpurea [Syn. Psammaplysilla purpurea] 99, 101. Druinella sp. 74, 75, 81, 82, 106, 110, 112. Dysidea avara 715, 716. Dysidea elegans 732, 734. Dysidea fragilis 829, 830. Dysidea herbacea 122, 123, 125, 126, 129, 130, 132, 135. Dysidea sp. 32, 146. E Echinoclathria sp. 207, 208, 209, 270. Echinodictyum sp. 511. Ecionemia geodides 394, 410, 411, 419. Ecteinascidia thurstoni 604. Ecteinascidia turbinata 289, 597, 598, 599, 600, 601, 602, 603, 604, 629, 630, 866. Enteromorpha intestinalis 911, 912. Epipolasis kushimotoensis 695, 696, 697. Erythrobacter sp. 145. Eudistoma cf. rigida 512. Eudistoma sp. 393, 412, 426, 427. Euplexaura nuttingi 652, 653, 654, 661, 662, 663, 664, 665. Euplexaura robusta 652, 653, 654, 655, 656. Eusynstyela latericius 432, 433, 434, 435. F Fasciospongia rimosa 152. Fasciospongia sp. 737, 748, 749, 750, 755. Fusarium sp. 179. G Geodia exigua 691. Geodia gigas 658. Gersemia Antarctica 224. Glossodoris quadricolor 149. Gymnodinium breve [Syn. Ptychodiscus brevis] 820. Gymnodinium selliforme 855. Gymnodinium sp. 854.

H Halichondria okadai 295. Halichondria sp. 38, 39, 40, 41, 42, 43, 47, 63, 673, 680, 686, 690, 693. Halichondria spp. 452. Haliclona cribicutis 596. Haliclona cribricutis 611. Haliclona densaspicula 922, 923. Haliclona sp. 18, 19, 39, 213, 214, 276, 277, 279, 941, 942. Haliclona tulearensis 309, 831. Haliclona viscosa 211, 266, 267. Halimeda xishaensis 832. Halocynthia roretzi 667. Halomonas sp. GWS-BW-H8hM 799, 800, 801, 803. Hamacantha sp. 523, 524. Haminoea fusari 215, 216, 217, 218, 219, 220. Haminoea navicula 221, 222, 223. Haminoea orbignyana 215, 216. Haminoea orteai 221, 222, 223. Haraldiophyllum sp. 2. Heterosiphonia japonica 890, 891, 892. Hexabranchus sanguineus 38, 72, 73. Hexabranchus sp. 51, 52, 53, 55, 56. Himerometra magnipinna 76. Hippospongia lachne 751. Hippospongia sp. 731, 733, 735. Histodermella sp. 369. Holiclona sp. 966. Homarus americanus 224. Homarus vulgaris 224. Homaxinella sp. 560. Homophymia sp. 315, 316, 322, 323. Hyatella sp. 148. Hymeniacidon sanguinea 658. Hymeniacidon sp. 463, 698, 698, 700. Hyphomycetes sp. 528. Hyrtios sp. 526, 527. I Ianthella flabelliformis 93. Ianthella sp. CMB-01245 929,930, 931, 932, 933. Igernella notabilis 753, 754. Iotrochota baculifera 841, 842, 843, 844, 894, 895, 896, 897, 898, 899, 900, 901, 902, 903, 904, 959, 971. Iotrochota sp. 971.

Index 3 Compound Organism Source Index

J Janibacter limosus HeL 1 310. Jaspis cf. coriacea 8, 9. Jaspis sp. 5, 6, 7, 10, 11, 12, 13, 14, 38, 39, 47, 48, 49, 50, 657. Jorunna funebris 605. K Kandelia candel 714, 745. Kirkpatrickia variolosa 858, 882, 883. L Latrunculia apicalis 339, 342. Latrunculia bellae 325, 328, 334, 345, 352. Latrunculia brevis 340, 343, 344. Latrunculia corticata 148, 149. Latrunculia fiordensis 338, 354. Latrunculia magnifica 148, 149, 150, 151. Latrunculia purpurea 347. Latrunculia sp. 335, 336, 337, 341, 341, 348, 353, 354, 355. Latrunculia trivetricillata 340. Latrunculia wellingtonensis 338, 340, 345, 382. Leiodermatium sp. 61, 62. Leptoclinides sp. 395, 397. Leptogorgia gilchristi 652. Leptogorgia setacea 224. Leptogorgia virgulata 224. Leucascandra caveolata 20. Lignincola laevis 826. Lipastrotethya ana 707. Lissoclinum patella 157, 158, 159, 164, 165, 166, 965. Lissoclinum vareau 437, 438. Lyngbya bouillonii 153. Lyngbya majuscula 117, 118, 119, 120, 121, 133, 137. Lyngbya sp. 874. M Marinispora sp. NPS008920 21, 22. Marseniopsis mollis 224. Martensia fragilis 23. Marthasterias glacialis 658. Mechercharimyces asporophorigenens YM11-542 174. Membranipora perfragilis 453, 454. Microbispora aerata IMBAS-11A 116.

411

Micrococcus sp. 147. Microcosmus vulgaris 257. Microxina sp. 659. Monanchora pulchra 859, 860. Monodonta labio 476. Monostroma sp. 258. Moorea producens 124. Mycale magellanica 44, 45, 46. Mycale plumose 839, 840. Mycale sp. 64, 70, 71, 156, 827. Mytilus edulis 269, 270, 271, 272, 273. N Navanax inermis 222, 223, 229, 231. Neamphius huxleyi 834. Negombata sp. 348. Neopetrosia proxima 280. Nephteis fascicularis 291. Niphates sp. 227, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245. Nocardia sp. Acta 3026 25, 26. Nocardia sp. ALAA 175. Nostoc sp. 31 169, 170. O Occurs in animals and plants tissues, in DNA and RNA 644. Occurs in marine sediments 573. Occurs in plants, yeasts and fungi 233. Occurs in sponges 227. Oceanapia sagittaria 414, 416. Oceanapia sp. 97, 401, 416, 417, 452, 605, 712. Oscillatoria spongeliae 125. P Pachastrissa nux 52, 52, 53, 53, 55, 55, 57, 57, 58, 59, 60. Pachychalina sp. 950. Pelagiobacter variabilis 575, 578, 579, 580. Penares schulzei 871, 872, 873. Penares sp. 281. Penicillium aurantiogriseum 480, 481, 482, 893, 893. Penicillium aurantiogriseum SP0-16 839, 840. Penicillium citrinum N-059 910. Penicillium commune SD-118 473. Penicillium expansum Link MK-57 914, 915, 916.

412

Index 3 Compound Organism Source Index

Penicillium oxalicum 0312f1 477, 493. Penicillium paneum 176, 477, 493, 867. Penicillium sp. 178, 317, 318, 913, 914. Penicillium sp. OUPS-79 911, 912. Perna viridis 878. Perophora nameii 423. Petrosaspongia metachromia 735, 736. Petrosaspongia nigra 249. Petrosia seriata 302, 303, 304. Petrosia sp. 439, 440, 446. Petrosia spp. 452. Phidolopora pacifica 648, 666. Phloeodictyon sp. 808, 809, 810, 811, 812, 813, 814, 815, 816. Phomopsis sp. ZZ08 449. Phorbas sp. 68, 69. Phycopsis terpnis 703, 704. Phyllidia bourguini 699. Phyllidia ocellata 670, 680, 689, 689, 692, 742, 743. Phyllidia pustulosa 676, 681, 682, 683, 684, 686, 689, 691, 699, 704, 707. Phyllidia sp. 698, 707. Phyllidia varicosa 681, 698, 700, 705, 706, 744. Phyllidiella pustulosa 686, 694, 705, 706, 707. Plakina sp. 787, 788. Pocockiella variegata 575, 578, 579, 580. Poecillastra aff. tenuilminaris 825. Polycarpa aurata 161. Polycitorella sp. 39. Polyfibrospongia sp. 16, 17. Polysyncraton echinatum 393, 405, 412. Prianos melanos 340, 379. Prostheceraeus villatus 212, 311, 312. Protophlitaspongia aga 510. Psammaplysilla arabica 81, 82. Psammaplysilla purea 105, 106, 107, 108, 109, 110, 111. Psammaplysilla purpurea 76, 100, 110. Psammaplysilla purpurea [Syn. Druinella purpurea] 99, 101. Psammopemma sp 499, 500, 503. Pseudoalteromonas sp. CMMED 290 877. Pseudoceratina durissima 76, 89, 92. Pseudoceratina purpurea 84, 85, 103. Pseudoceratina sp. 104. Pseudoceratina verrucosa 105.

Pseudodistoma kanoko 283, 284, 285. Pseudodistoma megalarva 284, 285, 286, 287, 288. Pseudolabrus japonicus 622, 623, 624, 625, 626, 627, 628. Pseudomonas sp. 315, 316, 319, 322, 323. Pseudonocardia sp. SCSIO 01299 849, 968, 969, 970. Pseudopterogorgia elisabethae 946. Pteria muricata 282, 290. Pterocella vesiculosa 868, 869. Pterocladia capillacea 224. Ptychodiscus brevis [Syn. Gymnodinium breve] 820. R Raphoxya sp. 707. Rapidithrix sp. HC35 3, 4. Rapidithrix thailandica GB009 313. Reniera sarai 296, 297. Reniera sp. 246, 247, 248, 447, 448, 450, 456, 606, 607, 608, 609. Reniera spp. 452. Reticulidia fungia 729, 730. Rhizophora stylosa 470, 471, 472, 619. Ritterella tokioka 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557. S Saccharomonospora sp. CNQ-490 134. Salinispora tropica CNB-392 870. Sargassum thunbergii 845. Sceptrella sp. 340, 344, 356. Scytonema sp. 874. Shewanella piezotolerans WP3 478. Sinularia microclavata 308. Sinularia polydactyla 308. Smenospongia sp. 731, 733, 735, 739. Sphaeroides oblongus 486. Spongia irregularis 752. Spongia mycofijiensis 148. Spongia sp. 149, 731. Spongosorites sp. 516, 517, 518, 519, 520, 522. Stagonosporopsis cucurbitacearum 206. Stelleta sp. 406, 416, 421. Stelleta splendens 5, 6, 11.

Index 3 Compound Organism Source Index

Stelletta maxima 200, 201, 202, 203, 204, 205. Stelletta sp. 8, 9, 14. Stigonema sp. 874. Streptomyces griseus 797. Streptomyces olivaceus 558, 559. Streptomyces sp. 210, 564, 565, 574, 711, 745, 853, 879, 880, 881, 935, 936, 937. Streptomyces sp. Act8015 644. Streptomyces sp. B8251 573. Streptomyces sp. CHQ-64 713. Streptomyces sp. CNB-253 581, 582, 583, 584. Streptomyces sp. CP32 138, 139, 140, 141, 142, 143, 144. Streptomyces sp. HB202 586, 587, 588, 589, 590, 591. Streptomyces sp. HKI0595 714. Streptomyces sp. KORDI-323 256. Streptomyces sp. Merv8102 175. Streptomyces sp. NPS-698 837. Streptomyces sp. NTK 937 28. Streptomyces sp. SA-3501 509. Streptomyces sp. Sp080513GE-23 18, 19. Streptomyces sp. TP-A0597 143, 144. Streptomyces spp. 577. Streptomyces variabilis 307. Streptomyces venezuelae 802, 804, 805, 806, 807, 977. Streptomyces viridostaticus ssp. littoralis LL-31F508 592, 593, 594, 595. Strongylodesma algoaensis 325, 328, 334, 352. Strongylodesma aliwaliensis 380, 381. Stryphnus mucronatus 660. Stylissa caribica 956. Suberea clavata 86, 87, 88. Suberea mollis 76, 91, 113. Suberea sp. 529, 530. Suberites sp. 29, 30, 463, 861, 862, 863. Symbiodinium sp. 875. Symploca sp. 131. Synoicum pulmonaria 27. Synoicum sp. 499, 500, 501. T Tedania ignis 147. Terrestrial bacterium Nocardiopsis cirriefficiens 181.

413

Terrestrial bacterium Streptomyces caeruleus 183. Terrestrial cyanobacterium Westiellopsis prolific 33. Terrestrial fungus Eupenicillium sp. PF1140 178. Terrestrial fungus Isaria farinose 493. Terrestrial fungus Penicillium expansum MK-57 911, 912. Terrestrial streptomycete Streptomyces caeruleus 181. Terrestrial streptomycete Streptomyces sp. 802, 804, 805. Tethya aurantium 632. Theonella sp. 171, 172, 173, 459. Theonella swinhoei 259, 260, 261, 262. Thermoactinomyces sp. TA66-2 116. Thermoactinomyces sp. YM3-251 167. Thorectandra sp. 972. Topsentia sp. 688, 689. Toxopneustes pileolus 250. Trididemnum sp. 427. Trikentrion loeve 741. Tsitsikamma favus 325, 328, 329, 331, 334, 352, 383, 384. Tsitsikamma pedunculata 325, 328, 334, 352. Tubastraea faulkneri 65, 66, 67. Tylodina perverse 74. U Unidentified ascidian 33, 163, 414, 415, 416, 417, 427, 457, 458, 575, 578. Unidentified ascidian (family Polyclinidae) 817, 818. Unidentified bryozoan 454. Unidentified fungus (class Eurotiomycetes) 965. Unidentified green alga NIO-143 651. Unidentified lithistid sponge (family Neopeltidae) 24, 54. Unidentified mangrove 145, 449. Unidentified marine bacterium He159b 233. Unidentified marine bacterium LL-14I352 575, 578. Unidentified red alga (family Delesseriaceae) 1. Unidentified sponge 206, 225, 226, 228, 357, 358, 383, 384, 703. Unidentified sponge (family Jaspidae) 5, 6.

414

Index 3 Compound Organism Source Index

Unidentified sponge (family Latrunculidae) 330. Unidentified sponge (family Spongiidae) 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728. Unidentified sponge (order Haplosclerida, family Petrosiidae) 934, 944. Unidentified sponge (order Verongida) 321. V Verongia aerophoba 74, 75, 89. Verongia cavernicola 89, 91, 98. Verongia thiona 91. Verongula rigida 74. Verongula sp. 89, 111. Vibrio anguillarum 775 115. Vibrio sp. 115. X Xestospongia caycedoi 455, 610. Xestospongia cf. carbonaria 388, 404, 420.

Xestospongia cf. exigua 420. Xestospongia exigua 300, 301, 305, 306. Xestospongia ingens 947, 948, 949, 952, 953. Xestospongia sp. 194, 298, 299, 301, 302, 303, 450, 451, 278, 462, 612, 613, 614, 615, 616, 617, 618. Xestospongia spp. 300, 404, 452. Xylaria sp. 2508 884. Xylocarpus granatum 268. Z Zoanthus sp. 528, 962, 963, 964. Zyzzya cf. fuliginosa 369, 372, 373, 374, 377. Zyzzya fuliginosa 332, 333, 337, 363, 364, 365, 366, 367, 368, 370, 371, 372, 373, 374, 375, 376, 378, 385, 649, 885, 886, 887, 888. Zyzzya massalis 327, 363, 364, 365, 366, 367. Zyzzya sp. 973. Zyzzya spp. 347, 371, 373.

Index 4 Compound Sampling Geographic Locality Index In this index, all geographic locations in HAMNP Volume 4 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 196 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 "Handbook of Active Marine Natural Products Volume 4" and a number code sequence of the related compounds follows the detail information immediately. There are 678 related compounds with geographic information in HAMNP Volume 4. 1 CHINA China, Bohai Sea 480, 481, 482, 893. China, China waters 179, 449, 634, 839, 840, 907. China, Dalian, Liaoning 889. China, Hainan I. 894. China, Hainan 707, 841, 842, 843, 844, 895, 896, 897, 898, 899, 900, 901, 902, 903, 904, 959, 971. China, Lingshui Bay, Hainan 707. China, Mngolian Jilantai Salt Field 974, 975, 976. China, Pingtan I., Fujian 845. China, presumably China 470, 471, 472, 619. China, Weihai, Shandong 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 197, 198, 199. China, Weizhou I., Guangxi 652, 653, 654, 655, 656.

China, Xisha Is., South China Sea 466, 467, 468, 469, 832. China, Yalong Bay, Hainan 689, 694. China, Yantai, Shandong 890, 891, 892. Hong Kong, Mai Po 884. South China Sea, South China Sea 176, 317, 477, 493, 672, 849, 867, 908, 909, 917, 918, 968, 969, 970. South China Sea, Yongxing I., South China Sea, China 751. 2 JAPAN Japan, Atami-shi, Shizuoka prefecture 206. Japan, Ayamaru coast of Amami Is. 962, 963, 964. Japan, Hachijo-jima I. 689, 689, 692, 692, 692, 694, 695, 707. Japan, Japan waters 44, 45, 46, 64, 70, 71, 84, 172, 173, 191, 195, 196, 200, 201, 202, 203,

416

Index 4 Compound Sampling Geographic Locality Index

204, 205, 295, 476, 506, 532, 560, 657, 671, 683, 684, 914, 915, 916, 924, 925, 926, 927, 928, 945, 954. Japan, Kamikoshiki-jima I. 680. Japan, Kamikoshiki-jima, Shimokoshiki I. 681. Japan, Katsuura, Kii Penisula 682. Japan, Kuchinoerabu, Tanegoshima I. 704. Japan, Oshima, Kagoshima prefecture 691. Japan, Oshima-Shinsone 955, 957. Japan, Shimokoshiki I. 744. Japan, Tateyama City, Chiba 18, 19. Japan, Tsutsumi I., Fukuoka prefecture 695. Japan, Ukeshima Is. 817, 818. Japan, Usa Bay, Kochi prefecture 879, 880, 881. Japan, Yakushima I. 686. Japan, Yakushima, Kuchinoerabu-jima Is. 691. Japan, Yakushima, Kuchinoerabu-jima, Tenegashima Is. 689. Okinawa, Kerama I. 168, 321, 833. Okinawa, off Ishigaki I. 38, 39, 47, 48, 49, 50. Okinawa, Okinawa 40, 41, 42, 43, 106, 107, 108, 109, 110, 110, 111, 146, 152, 171, 207, 208, 209, 237, 238, 239, 240, 241, 259, 260, 261, 262, 263, 264, 265, 283, 284, 284, 285, 298, 299, 300, 301, 301, 302, 303, 305, 306, 393, 394, 408, 459, 526, 527, 529, 530, 703, 704, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 836, 952. Okinawa, Seragaki 526, 527. Okinawa, Unten Port 29, 30, 693, 861, 862, 863. 3 RUSSIA Sea of Okhotsk, Russia Sakhalin Bay, Sea of Okhotsk 324. Sea of Okhotsk, Russia Sea of Okhotsk 859, 860. 4 KOREA WATERS Korea waters, 344, 356. 5 R. O. KOREA Jeju I. Jeju I. 942. Keomun I. 922, 923. Kyung-Po Kyung-Po 576, 585.

6 ASIA India waters 439, 440, 446, 596, 611. India Mandapam coast 605. India Mandapam Tamil, Nadu 110. Indian Ocean, South Africa coast 765, 766, 770. Indian Ocean South Indian Ocean 357, 358. Indian Ocean Southwest Indian Ocean 558, 559. Indonesia 276, 277, 278, 279, 369, 432, 433, 434, 435. Indonesia Ambon 161. Indonesia Menjangan I., Bali 645. Indonesia Pramuka I. 705, 706. Indonesia Sulawesi 783, 784. Indonesia Tulamben Bay, Bali 95. Maldives 441, 442, 447, 456. Philippines Mactan I., Cebu 138, 139, 140, 141, 142. Philippines Negros I., Cebu I., San Sebastian, Cebu 676. Philippines 34, 376, 423, 712, 737, 821, 822, 823, 824. Red Sea 99, 100, 148, 148, 149, 150, 242, 243, 412, 412, 426, 427. Sri Lanka Colombo 707. Thailand 612, 613, 614, 615, 616, 617, 688, 689, 732, 734. Thailand Chumphon I., Surat Thani province 52, 53, 55, 57, 58, 59. Thailand Chumphon National Park 60. Thailand Gulf of Thailand 414, 416. Thailand Koh Tao, Surat Thani province 60. Thailand PP I., Andaman Sea, Southern Thailand 690. Vietnam 686, 694, 705, 706. Vietnam Vang Fong Bay 465. 7 AUSTRALIA Australia 5, 6, 14, 97, 522, 659, 731, 821, 822, 823, 824, 885, 886, 887, 888. Australia Bass Strait, Tasmania (State) 454, 487, 929, 930, 931, 932. Australia Bathurst Harbour, Tasmania 838. Australia Bougainville Reef, Queensland 451. Australia Coral Gardens, Gneerings Reef, Mooloolaba 676. Australia Holmes Reef, Coral Sea 104.

Index 4 Compound Sampling Geographic Locality Index

Australia Jamieson Reef, Bonaparte Archipelago 8, 9, 14. Australia Moorina Bay, Tasmania 394, 410, 411, 419. Australia Mudjimba I., Mooloolaba 674, 689, 742, 743. Australia Northern Rottnest Shelf, Western Australia 961. Australia Pugh Shoal, Northern Territory 31, 717, 737, 738, 846. Australia Tani’s Reef, Gneerings Reef, Mooloolaba 689, 692, 695. Australia Weed Reef, Darwin 676. Great Barrier Reef, 7, 10, 11, 12, 13, 33, 90, 276, 277, 674, 675, 701, 702. Great Barrier Reef, Australia Liizard I. 130. Queensland 86, 87, 88. Queensland Coral Sea 934, 944. Queensland Farquharson Reef 393, 405, 412. Queensland Heron I. 674. Queensland Palm I. 848. Queensland Pelorus Is. 674, 675, 676, 689, 692. Queensland Rodda Reef 973. Queensland Shelburne Bay 93. Southern Australia 453, 454, 933. Tasmania 487. Western Australia 864, 865, 959, 960. Western Australia Western Australia coastline 68, 69. 8 OCEANIA Federated States of Micronesia 99, 102, 103, 225, 291. Federated States of Micronesia Ant Atoll, Pohnpei I. 194, 695, 697. Federated States of Micronesia Arno Atoll 389, 390. Federated States of Micronesia Mante Channel, Pohnpei I. 415, 416, 417, 427. Federated States of Micronesia Mutok Harbor, Pohnpei I. 689, 704. Federated States of Micronesia Pohnpei I. 194, 333, 370, 371, 372, 373, 374, 375, 704, 829. Federated States of Micronesia Truk 401, 416, 417.

417

Fiji 5, 6, 11, 74, 75, 81, 82, 99, 106, 110, 112, 332, 337, 363, 364, 365, 366, 367, 368, 378, 385, 398, 400, 402, 417, 427, 428, 448, 455, 575, 578, 610, 685, 688. Fiji Nacula I., Yasawa I. 711. New Zealand 32, 156, 339, 341, 353, 854, 855. New Zealand Wellington 382. Palau, Oceania 286, 287, 288, 510, 575, 578, 579, 580, 748, 749, 750, 755, 798, 819, 972. Palau, Oceania Koror 483, 484, 485. Palau, Oceania near Uchelbeluu Reef 61, 62. Palau, Oceania Urukthapel I. 388, 404, 420. Papua New Guinea 8, 9, 15, 128, 132, 302, 304, 732, 734, 752, 947, 949, 953, 965. Papua New Guinea Kape Point 131. Papua New Guinea Kolaio I. 131. Papua New Guinea New Britain I. 796. Solomon Is. 391, 392, 403, 431. Solomon Is. Vangunu I. 746, 747. Vanuatu 369, 372, 373, 374, 377, 781, 785, 786, 789, 790. 9 EUROPE Adriatic Sea, Croatia Limski canal, N. Adriatic Sea, Croatia 632. Baltic Sea Kiel Fjord 574. France Villefranche-Sur-Mer 488, 489, 491, 492, 494, 495, 496, 497, 507, 508. Ireland Bruckless, Donegal 273. Italy Bay of Naples, Procida, Punta Pizzaco 257. Italy Bay of Taranto 689, 692, 695. Italy Fusaro Lake, Gulf of Naples 215, 216, 217, 218, 219, 220. Italy Naples 296. Italy Taranto, near Porto Cesareo 676. Mediterranean Sea 297, 397, 689, 835, 913, 914. Mediterranean Sea Cabo de Gata, Southern Spain 919, 920, 921. Mediterranean Sea Catalonia, Northwestern Spain 921. Mediterranean Sea France 660. North Sea 310. Norway Troms, Northern Norway 27. Norway waters off Bergen 212, 311, 312. Spain 215, 216, 221, 222, 223, 515.

418

Index 4 Compound Sampling Geographic Locality Index

10 AFRICA Comoros Is. 429, 430, 436. Comoros Is. Mayotte lagoon 154, 155. Kenya Lamu I. 827. Madagascar Salary Bay 457, 458. Mozambique near Ponto Malongane 652. Senegal 1, 741. Seychelles Seychelles 393. South Africa 309, 325, 328, 329, 330, 331, 334, 352, 380, 381, 383, 384, 776, 831. South Africa off South Africa’s temperate Southern coast 761. Tanzania Misali I. 678, 679. Tanzania Pemba I. 246, 247, 248, 652, 653, 654, 661, 662, 663, 664, 665. West Africa W. African Coast 115. 11 USA Alaska, USA Aleutian Is., coast of Alaska 335, 336, 337, 341, 355. California, USA 697. California, USA Bodega Bay 581, 582, 583, 584. California, USA La Jolla 134. Florida, USA Fort Pierce 646. Guam, USA 21, 22, 388, 791, 792, 802, 804, 805, 806, 807, 977. Guam, USA Blue Hole 707. Guam, USA Gun Beach 680. Hawaii, USA 700. Hawaii, USA North coast of O’ahu 680, 686. Hawaii, USA Pupukea, north shore of O’ahu 700. Oregon, USA Waldo Lake 874. Puerto Rico 78, 79, 80. Puerto Rico Mona I. 280. Texas, USA Galveston Bay 828, 850, 851, 852. Texas, USA Trinity Bay, Galveston 145. Virgin Is, USA 121. 12 NORTH AMERICA Canada Conehead Point, Rennell Sound, Graham I., British Columbia 675, 676. Guatemala Pacific coast 213, 214. Gulf of Mexico 573. Gulf of Mexico Laguna de Terminos 210.

Mexico Gulf of California 677. Mexico Isabel I., Nayarit 674. 13 CARIBBEAN SEA Bahamas Caribbean Sea 94, 96, 251, 326, 346, 629, 630, 837, 866, 951, 956. Bahamas Sweetings Cay 307. Caribbean Sea 77, 83, 98, 111, 117, 118, 137, 177, 177, 177, 177, 359, 360, 562, 598, 649. Curacao, Netherlands Antilles, Caribbean Sea 874. Curacao I., Caribbean Sea 118, 119, 120. Jamaica 54. Jamaica off northwest coast 24. 14 SOUTH AMERICA Argentina Patagonia 514. Brazil 424, 425, 650, 938, 950, 951. Colombia Santa Marta Bay, Caribbean Sea 676. 15 PACIFIC OCEAN Caledonia 315, 316, 322, 323. New Caledoinia (Fr.) 20, 249, 808, 809, 810, 811, 812, 813, 814, 815, 816. Pacific Ocean 148, 148, 966. Pacific Ocean Mariana Trench 566, 567, 568, 569, 570, 571, 572. Pacific Ocean Pacific I. 122, 123, 126, 129, 135. 16 ATLANTIC OCEAN Atlantic Ocean near South Georgia I. 499, 500, 501, 502, 503. Atlantic Ocean South Georgia I. 504, 505. Bermuda 650. Canary Basin 797. 17 ANTARCTIC/ARCTIC Antarctic 224, 224, 320, 339, 342, 503, 858, 882, 883. Antarctica Palmer Station 348, 499. Arctic 211. Kongsfjorden, Spitsbergen, Arctic Ocean Kongsfjord, inlet on west coast of Spitsbergen, Svalbard, Arctic Ocean 266, 267.

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. 2 25 kinds of PKs inhibitors 503. A A good candidate for an osteoporotic drug 962. A new class of multidrug resistance reversing agents 864. A new lead for antimalarial drug 838. Acetylcholinesterase inhibitor 313, 574. AChE modulator 890, 891, 892. Actomyosin ATPase activator 649. Affinity to adenosine receptors, strong affinity to A1-adenosine receptors 417. Affinity to adenosine receptors, strong affinity to A2-adenosine receptors 417. Affinity to benzodiazepine binding sites of GABAA receptors 417. Affinity to benzodiazepine binding sites of GABAA receptors, strong 416. Alarm pheromone 215, 216, 217, 218, 219, 220, 221, 222, 223, 231. Aldose reductase inhibitor 945, 954. Algicide 666. Algicide, Cochlodinium polykrikoides 116. Allelopathic 170. An important biological source of superoxide radicals 377. Analgesic 17. Analgesic, peripheral 16. Anthelminthic 5, 6, 136. Anthelmintic 11, 685, 687, 688. Antialgal 169. Anti-Alzheimer’s agents, potential 929, 931, 932. Anti-angiogenic, HUVECs 756, 757, 758, 759. Anti-angiogenic, K562 756, 757, 758, 759. Anti-angiogenic, KB 756, 757, 758, 759. Anti-angiogenic, neuro-2a 756, 757, 758, 759. Anti-angiogenic, NHDF 756, 757, 758, 759.

Antibacterial 27, 90, 224, 225, 266, 267, 335, 355, 445, 446, 447, 528, 607, 608, 609, 618, 668, 669. Antibacterial inactive, Bacillus subtilis 28. Antibacterial inactive, Bacillus thuringiensis SCSIO BT01 970. Antibacterial inactive, Enterobacter aerogenes 230. Antibacterial inactive, Enterococcus faecalis ATCC 29212 970. Antibacterial inactive, Escherichia coli 799, 800, 801. Antibacterial inactive, Escherichia coli ATCC 25922 942. Antibacterial inactive, Escherichia coli DC 2 516, 519, 520. Antibacterial inactive, Escherichia coli NIJ JC2 192, 193. Antibacterial inactive, gram-positive and negative bacteria 561. Antibacterial inactive, Klebsiella oxytoca 1082 E 516, 519, 520. Antibacterial inactive, Micrococcus luteus 444. Antibacterial inactive, PRSP clinical isolate 442, 596. Antibacterial inactive, Pseudomonas aeruginosa 230, 339, 341. Antibacterial inactive, Pseudomonas aeruginosa 1592E 516, 519, 520. Antibacterial inactive, Pseudomonas aeruginosa 1771 516, 519, 520. Antibacterial inactive, Pseudomonas aeruginosa 1771M 516, 519, 520. Antibacterial inactive, Sarcina lutea 459. Antibacterial inactive, Staphylococcus aureus ATCC 29213 970. Antibacterial inactive, Staphylococcus epidermidis 563, 645. Antibacterial inactive, Staphylococcus lentus 587.

420

Index 5 Compound Pharmacological Activity Index

Antibacterial inactive, Streptococcus aureus 285 519, 520. Antibacterial inactive, Streptococcus aureus 503 519, 520. Antibacterial inactive, Streptococcus aureus SG 511 519, 520. Antibacterial inactive, Streptococcus pyogenes 308A 519, 520. Antibacterial inactive, Streptococcus pyogenes 77A 519, 520. Antibacterial, 4 bacterial strains 179. Antibacterial, B-392 452. Antibacterial, Bacillus cereus 889. Antibacterial, Bacillus subtilis 32, 168, 175, 251, 278, 310, 329, 331, 339, 341, 383, 384, 386, 442, 452, 456, 459, 523, 524, 586, 588, 589, 590, 591, 597, 598, 599, 601, 606, 712, 783, 784, 799, 800, 801, 853, 861, 935, 936, 937. Antibacterial, Bacillus subtilis ATCC 6633 562, 942. Antibacterial, Bacillus subtilis in vivo 798. Antibacterial, Bacillus subtilis PCI 189 192, 193, 252. Antibacterial, Bacillus subtilis Presque Isle 620 596. Antibacterial, Bacillus thuringiensis SCSIO BT01 849, 968, 969. Antibacterial, Candida albicans 787. Antibacterial, Clostridium perfringens 581, 582. Antibacterial, Corynebacterium xerosis IFM 2057 192, 193, 252. Antibacterial, Cryptococcus neoformans 693. Antibacterial, Enterobacter cloacae 889. Antibacterial, Enterococcus faecalis 21, 22. Antibacterial, Enterococcus faecalis ATCC 29212 849, 968, 969. Antibacterial, Enterococcus hirae 576, 585. Antibacterial, Escherichia coli 78, 79, 80, 168, 176, 181, 183, 278, 339, 341, 348, 456, 477, 493, 493, 582, 712, 832, 845, 867, 892, 919, 920, 921. Antibacterial, Escherichia coli and Micrococcus luteus 393. Antibacterial, Escherichia coli ATCC 25922 950. Antibacterial, Escherichia coli NIJ JC2 252. Antibacterial, four oxacilin-resistant Staphylococcus aureus 950.

Antibacterial, gram-negative bacterium Pseudomonas aeruginosa 829, 830. Antibacterial, gram-positive and -negative bacteria 143, 144, 462, 580, 808, 816. Antibacterial, gram-positive bacteria 99, 100, 238, 239, 240, 251, 450, 459, 605. Antibacterial, gram-positive bacterium Bacillus subtilis 868, 869. Antibacterial, Hemophilus influenzae 581. Antibacterial, Micrococcus luteus 168, 175, 348, 576, 585, 673, 693, 861, 919, 920, 921. Antibacterial, Micrococcus luteus IFM 2066 192, 193, 252. Antibacterial, Micrococcus luteus IFO 12708 942. Antibacterial, Micrococcus luteus, MMOA: sortase A inhibitor 356. Antibacterial, MRSA 714, 745, 877. Antibacterial, Mycobacterium sp. 459. Antibacterial, natural active, synthetic inactive 175. Antibacterial, Neisseria gonorrheae ATCC 49226 441, 442, 443. Antibacterial, PRNG clinical isolate 441, 442, 443, 444, 596. Antibacterial, Proteus mirabilis 889. Antibacterial, Proteus vulgaris ATCC 3851 942. Antibacterial, Pseudomonas aeruginosa 78, 79, 80, 181, 183, 712. Antibacterial, Salmonella enteritidis 582. Antibacterial, Salmonella typhi 2. Antibacterial, Sarcina lutea 105. Antibacterial, Serratia marcescens 2, 348. Antibacterial, several gram-positive and negative bacteria, potent broad-spectrum antibiotics 483, 484, 485. Antibacterial, Staphylococcus aureus 3, 4, 78, 79, 80, 105, 168, 175, 176, 230, 251, 310, 315, 319, 348, 452, 456, 459, 477, 493, 493, 606, 712, 753, 787, 788, 799, 800, 801, 832, 845, 861, 867. Antibacterial, Staphylococcus aureus 209P 192, 193, 252. Antibacterial, Staphylococcus aureus ATCC 25923 950. Antibacterial, Staphylococcus aureus ATCC 29213 849, 968, 969. Antibacterial, Staphylococcus aureus ATCC 6538p 942.

Index 5 Compound Pharmacological Activity Index

Antibacterial, Staphylococcus aureus ATCC6538 562. Antibacterial, Staphylococcus aureus, MMOA: sortase A inhibitor and fibronectin binding 463. Antibacterial, Staphylococcus lentus 586, 588. Antibacterial, Staphylococcus sp. 21, 22. Antibacterial, Streptococcus aureus 285 516. Antibacterial, Streptococcus aureus 503 516. Antibacterial, Streptococcus aureus SG 511 516. Antibacterial, Streptococcus pneumoniae 21, 22. Antibacterial, Streptococcus pneumoniae ATCC 6303 442, 596. Antibacterial, Streptococcus pyogenes 308A 516. Antibacterial, Streptococcus pyogenes 77A 516. Antibacterial, Streptomyces sp. 85E 748, 749, 750, 755. Antibacterial, Streptomyces viridochromogenes 310. Antibacterial, strong inhibition of two sympatric bacterial strains 211, 212. Antibacterial, TB-causing Mycobacterium smegmatis and Mycobacterium bovis 276. Antibacterial, Vibrio anguillarum 452. Antibacterial, Vibrio ichthyoenteri 889. Antibacterial, Vibrio sp. 319. Antibacterial, VREF 714, 745. Antibiotic 455, 578, 579, 580, 803. Anticancer-Cell-Effect 118, 118, 118, 118, 133, 153, 905, 906. Anticyanobacterial 169. Antifeedant 47, 122, 123, 126, 129, 135. Antifeedant, amphipod Anonyx nugax and starfish 267. Antifeedant, feeding deterrent in marine organisms 224. Antifeedant, fish 274, 275. Antifeedant, for major Antarctic sponge predator 342. Antifeedant, reef fish Thalassoma bifasciatum 956. Antifoulant 99, 103, 224, 683, 684. Antifoulant phenoloxydase inhibitor 660. Antifoulant, barnacle Balanus amphitrite cypris larvae 708, 709, 710.

421

Antifoulant, bryozoan Bugula neritina larvae 318. Antifoulant, bryozoan Bugula neritina larval settlement 908, 909. Antifoulant, crustacean metamorphosis inhibitor 703. Antifoulant, inhibits microfouling 263, 264, 265. Antifoulant, inhibits settlement and metamorphosis of barnacle larvae 84, 85, 671. Antifoulant, inhibits settling of larvae of barnacle Balanus amphitrite 510. Antifoulant, larvae of acorn barnacle Balanus amphitrite 677, 678, 679, 680, 681, 682, 686, 690, 691, 694, 695, 705, 706, 707, 744. Antifoulant, larval settlement inhibitor 703. Antifungal 39, 53, 178, 195, 196, 225, 238, 239, 240, 276, 277, 310, 359, 360, 362, 419, 456, 513, 525, 531, 648, 666, 699, 791, 792, 966. Antifungal inactive, Aspergillus niger 526, 527. Antifungal inactive, Candida albicans 230, 339, 799, 800, 979. Antifungal inactive, Candida albicans ATCC 90028 193. Antifungal inactive, Cryptococcus neoformans 526, 527. Antifungal inactive, Cryptococcus neoformans ATCC 90113 77. Antifungal inactive, Micrococcus luteus 442. Antifungal inactive, Trichophyton mentagrophytes ATCC 40769 192. Antifungal, Alternaria brassicae 176, 477, 493, 493, 867. Antifungal, Aspergillus niger 29, 30, 168, 176, 477, 493, 493, 867. Antifungal, Aspergillus niger ATCC 40406 192, 193, 252. Antifungal, azole-resistant Candida albicans 206. Antifungal, Candida albicans 5, 6, 7, 10, 11, 12, 13, 20, 24, 68, 69, 72, 73, 157, 158, 159, 168, 181, 183, 341, 452, 523, 524, 629, 630, 712, 783, 788, 829, 830, 861, 862, 863, 917, 918, 978. Antifungal, Candida albicans ATCC 14503 194. Antifungal, Candida albicans ATCC 90028 192, 252, 442.

422

Index 5 Compound Pharmacological Activity Index

Antifungal, Candida albicans UCD-FR1 194. Antifungal, Candida glabrata 194. Antifungal, Candida krusei 194. Antifungal, Candida sp. 835. Antifungal, Coniella diplodiella 176, 477, 493, 493, 867. Antifungal, Cryptococcus neoformans 168, 523, 524, 861. Antifungal, Cryptococcus neoformans ATCC 900112 192, 193, 252. Antifungal, Cryptococcus neoformans ATCC 90112 442. Antifungal, erg6 mutant of Saccharomyces cerevisiae 506. Antifungal, Fusarium oxysporium 867. Antifungal, Fusarium oxysporium f. sp. vasinfectum 176, 477, 493, 493. Antifungal, Fusarium vasinfectum 867. Antifungal, Mucor miehei 210. Antifungal, Paecilomyces variotii YM-1 192, 193, 252. Antifungal, pathogenic fungi 64. Antifungal, Physalospora piricola 176, 477, 493, 493, 867. Antifungal, Saccharomyces cerevisiae 829, 830, 858. Antifungal, several pathogenic fungi 206. Antifungal, Trichophyton mentagrophytes 32, 168, 693, 861, 868, 869. Antifungal, Trichophyton mentagrophytes ATCC 40769 193, 252. Antifungal, Valsa ceratosperma 805. Antiglaucoma 148. Anti-HCV 335, 355. Antihistaminic, gpg ileum 83. Anti-HIV, CEM-4 HIV-1 infection assay 741. Anti-HIV, Haitian RF strain of HIV-I 102. Anti-HIV-1 323. Anti-HIV-1 IIIB, binding capacity to HIV-1 targets, recombinant protein Vif 843, 844, 896, 900, 901, 902. Anti-HIV-1 IIIB, binding capacity to HIV-1 targets, recombinant protein hmn APOBEC3G innate intracellular anti-viral factor 843, 844, 900, 901. Anti-HIV-1 IIIB, binding capacity to HIV-1 targets, recombinant protein gp41 843, 844, 900, 901.

Anti-HIV-1 IIIB, binding capacity, recombinant protein hmn APOBEC3G 896, 902. Anti-HIV-1 IIIB, MAGI test, MAGI cells 843, 844, 896, 900, 901, 902. Anti-HIV-1 IIIB, p24 antigen detection assay, MT4 cells 843, 844, 896, 900, 901, 902. Anti-HIV-1 IIIB, recombinant protein gp41 896, 902. Anti-HIV-1, IIIB, MAGI test, Hela-CD4-LTR-β-gal indicator cells 894, 895, 898, 899, 903, 971. Anti-HIV-1, IIIB, p24 antigen detection assay, MT4 cells 894, 895, 898, 899, 903, 971. Antihypertensive 125. Anti-inflammatory 119, 295, 746, 747, 798. Anti-inflammatory, RTX-induced mouse ear edema assay 866. Anti-inflammatoty, inflammatory disease model which measured IL-1b-induced PLA2 secretion, HepG2 133. Anti-invasive activity highly metastatic MDAMB-231 76, 91, 113. Antimalarial 60, 335, 355, 742, 743. Antimalarial, CRPF 104. Antimalarial, CRPF Dd2 838. Antimalarial, CSPF 3D7 838. Antimalarial, MRPF K1 52, 53, 55, 58, 59. Antimalarial, negative result, murine model in vivo, high levels of toxicity were observed 336, 337. Antimalarial, Plasmodium falciparum 323, 316, 322. Antimetastatic 295. Antimicrobial 81, 82, 241, 320, 321, 330, 340, 461, 573, 583, 584, 592, 593, 594, 595, 611, 649, 716, 731, 733, 735, 739, 941, 966. Antimicrobial, inhibits growth in two common water column microorganisms isolated from surrounding water 342. Antimigratory activity, wound healing assay, highly metastatic MDA-MB-231 76, 91, 113. Antimitotic 118, 119, 120, 121, 716. Antimutagenic 716. Antimycobacterial 280, 965. Antimycobacterial, Mycobacterium vaccae 853, 935, 936, 937.

Index 5 Compound Pharmacological Activity Index

Antimycobacterial, TB-causing Mycobacterium smegmatis and Mycobacterium bovis 277, 279. Antimydriatic 958. Antineoplastic, in vivo 27, 72, 234, 235, 236, 393, 407, 429, 430, 436, 456, 460, 463, 592, 593, 594, 595, 602, 603, 763, 775. Antineoplastic, in vivo, A549 293, 294. Antineoplastic, in vivo, B16 599. Antineoplastic, in vivo, hmn tumour cells 100. Antineoplastic, in vivo, inhibits migration and invasion of hmn breast cancer cells, possible scaffold for future design of breast cancer migration and invasion inhibitor 113. Antineoplastic, in vivo, investigated for treatment of a variety of hmn tumours including soft tissue sarcomas, osteosarcoma, melanoma and breast cancer 601. Antineoplastic, in vivo, Lewis lung carcinoma 599. Antineoplastic, in vivo, LX-1 599. Antineoplastic, in vivo, M5076 599. Antineoplastic, in vivo, MCF7 940. Antineoplastic, in vivo, MX-1 599. Antineoplastic, in vivo, OVCAR-3 363, 365. Antineoplastic, in vivo, P388 289, 293, 294, 363, 365, 599, 858. Antineoplastic, in vivo, phase II clinical trials 2003 granted orphan drug status by FDA 2004 for treatment of soft tissue sarcoma, mechanisms of action include inhibition of minor-groove-interacting transcription factors 601. Antineoplastic, in vivo, SN12k1 293, 294. Antineoplastic, in vivo, Tubulin polymerisation inhibitor 121. Antineoplastic, in vivo, U251 293, 294. Antineoplastic, in vivo, WiDr 940. Antioxidant 23. Antioxidant, DPPH radical scavenger 18, 19, 566, 567, 568, 569, 971, 974, 975, 976. Antioxidant, free radical scavenger 825. Antioxidant, high inhibition of xanthine oxidase 377. Antioxidant, radical scavenger 451. Antiplasmodial inactive, CRPF W2 675. Antiplasmodial inactive, CSPF D6 675.

423

Antiplasmodial, CRPF 905, 906. Antiplasmodial, CRPF W2 674, 689, 692, 697. Antiplasmodial, CSPF D6 674, 689, 692, 697. Antiplasmodial, inhibits both CSPF and CRPF, very low nmol/L level with strong cytotoxicity 973. Antiplasmodial, Plasmodium falciparum 95, 711. Antiplasmodial, Plasmodium falciparum D6 676, 698, 701, 702, 704. Antiplasmodial, Plasmodium falciparum K1 686. Antiplasmodial, Plasmodium falciparum NF 54 686. Antiplasmodial, Plasmodium falciparum various strains 934, 944. Antiplasmodial, Plasmodium falciparum W2 676, 698, 701, 702, 704. Antiproliferation, Hela 96. Antiproliferative 119, 804, 913, 914. Antiproliferative, J774 257. Antiproliferative, mammalian cell 118. Antiproliferative, mouse broblast cells 797. Antiproliferative, WEHI-164 257. Antiserotonergic 177. Antiserotonin 649. Antitrypanosomal, Trypanosoma brucei brucei 393, 405, 487. Antituberculosis 796. Antituberculosis, Mycobacterium tuberculosis H37Rv 92, 94, 946, 950. Antitussive 409. Antiviral 407, 429, 430, 436, 464, 644. Antiviral, HSV-1 16. Antiviral, influenza A H1N1 474, 475, 479, 620, 621, 635, 640, 641, 642, 643. Antiviral, inhibits growth of feline leukaemia virus 89. Antiviral, RSV 314. Antiviral, TMV virus 493, 493. Aromatase inhibitor 801. ATPase inhibitor 81, 82. ATP-citrate lyase inhibitor 971. B Binding affinity for metal ions Fe3+, Cu2+ and Zn2+ 558, 559. Binding capacity to HIV-1 targets 841, 842, 959.

424

Index 5 Compound Pharmacological Activity Index

Binding capacity to HIV-1 targets, recombinant protein gp41 894, 895, 898, 899, 903, 971. Binding capacity to HIV-1 targets, recombinant protein hmn APOBEC3G 894, 895, 898, 899, 903, 971. Binding capacity to HIV-1 targets, recombinant protein Vif 894, 895, 898, 899, 903, 971. Biogenetic precursor of manzamine alkaloids 833. Blocker of voltage sensitive Na+channel, neuro2a 133. Blocks binding of [3H]-methyl quinuclidinyl benzilate to muscarinic receptor, subtype M1, M2, M3 200, 201, 202, 203, 204, 205. Bronchodilator 511. C Ca2+ release agent 393, 398. Calcineurin inhibitor 752. Calcium channel blocker 301. Calcium release activity 399. Calcium release inducer, from sarcoplasmic reticulum, twenty times more potent than caffeine 259, 260, 261, 262. Calmodulin antagonist 512, 283, 284. cAMP inhibitor 439, 440. Carboxylate anion inhibited p53/MDM2 protein binding 131. Cardioactive 511. Cardiovascular 308. Caspase-3 inhibitor 974, 975, 976. cdc2 Kinase inhibitor 659. CDK inhibitor 883. Cell cycle effects, producer of G1 arrest 906. Cell cycle inhibitor 801. Cell cycle modulator 837. Cell division inhibitor, fertilised sea urchin eggs 51, 52, 53, 55, 56. Cell division inhibitor, fertilized sea urchin embryo assay 133. Cell division inhibitor, sea urchin eggs 715, 716. Cell growth inhibitor 445, 762, 764, 765, 766, 774, 777. Cell growth inhibitor, powerful 763. Cell proliferation inhibitor 24, 72, 73, 421, 426.

Cell proliferation inhibitor, mammalian 96. Cell reaggregation inhibitor 490. c-erbB-2 Kinase inhibitor 720. c-erbB-2 Kinase inhibitor inactive 718, 719, 721. Chelating agent 417. CNS activity 511, 1. Collagenase inhibitor, Clostridium histolyticum collagenase 657. COMPARE analyses were positive 761, 771, 770, 778, 779. COX inhibitor, hmn COX-2 564, 565, 577. COX inhibitor, ovine COX-1 564, 565, 577. cPLA2 exhibits specificity for release of arachidonic acid from membrane phospholipids, compounds that inhibit cPLA2 activity have been targeted as antiinflammatory agents 282, 290. cPLA2 inhibitor 282, 290. Cyclooxygenase-2 inhibitor 875. Cysteine protease inhibitor 191. Cytochalasin-like activity 148. Cytokinin 651. Cytotoxic 15, 20, 33, 67, 90, 128, 160, 166, 241, 242, 245, 256, 270, 278, 280, 283, 329, 331, 359, 360, 362, 369, 382, 383, 384, 388, 393, 404, 405, 420, 445, 461, 462, 488, 489, 491, 492, 494, 495, 496, 497, 506, 507, 508, 577, 578, 579, 580, 754, 762, 764, 774, 776, 777, 791, 792, 822, 823, 824, 825, 834, 835, 836, 853, 870, 935, 936, 937, 947, 949. Cytotoxic inactive, A2780 74, 75, 81, 82, 106, 802, 804, 806, 807, 904. Cytotoxic inactive, A549 182, 183, 184, 185, 187, 188, 189, 190, 207, 518, 802, 804, 806, 807, 904. Cytotoxic inactive, Bel7402 802, 804, 805, 806, 807, 904, 977. Cytotoxic inactive, BGC823 802, 804, 806, 807, 904. Cytotoxic inactive, cultured KB-3 676. Cytotoxic inactive, DU145 596. Cytotoxic inactive, EAC 885. Cytotoxic inactive, HCT8 802, 804, 806, 807, 904. Cytotoxic inactive, HCT15 518. Cytotoxic inactive, HCT116 337, 364, 365, 378, 423, 432, 433. Cytotoxic inactive, HEK-293 213, 214.

Index 5 Compound Pharmacological Activity Index

Cytotoxic inactive, HeLa 317, 656, 804, 879, 880, 881. Cytotoxic inactive, HeLa-S3 162. Cytotoxic inactive, Hep2 317. Cytotoxic inactive, HL60 182, 183, 184, 185, 187, 188, 189, 190. Cytotoxic inactive, HT29 207. Cytotoxic inactive, J774.A1 213, 214. Cytotoxic inactive, K562 74, 81, 82, 106, 181, 189, 566, 567, 568, 569, 570, 656, 942, 974, 975, 976. Cytotoxic inactive, KB 106, 107, 108, 111, 181, 184, 189, 190, 259, 261, 284, 317, 323, 415, 701. Cytotoxic inactive, KBV200 317. Cytotoxic inactive, KM20L2 596. Cytotoxic inactive, KYSE70 652. Cytotoxic inactive, L1210 106, 107, 108, 111, 172, 459, 910. Cytotoxic inactive, LO2 672. Cytotoxic inactive, MCF7 31, 80, 738. Cytotoxic inactive, NCI-H460 416, 596, 970. Cytotoxic inactive, NIH-H460 802, 804, 805, 806, 807. Cytotoxic inactive, normal lymphocytes 716. Cytotoxic inactive, P388 207, 560, 596, 624, 962, 963. Cytotoxic inactive, panel of 6 HTCLs 802, 804. Cytotoxic inactive, panel of HTCLs 807. Cytotoxic inactive, SF295 596. Cytotoxic inactive, SK-MEL-2 518. Cytotoxic inactive, SMMC-7721 176. Cytotoxic inactive, SW1736 596. Cytotoxic inactive, SW1990 473. Cytotoxic inactive, Vero 291. Cytotoxic inactive, WEHI-164 213, 214. Cytotoxic inactive, WHCO5 652. Cytotoxic inactive, XF498 518, 520. Cytotoxic inactive, XRS-6 337, 378, 402, 409, 417. Cytotoxic, 3 tumour cell lines 179. Cytotoxic, 5637 394, 410, 411, 419. Cytotoxic, 786-0 514, 821. Cytotoxic, 95-D 317. Cytotoxic, A2780 110, 112, 713, 805, 900, 903, 977. Cytotoxic, A498 778, 779, 821. Cytotoxic, A549 24, 34, 35, 36, 37, 114, 137, 152, 154, 155, 167, 174, 181, 186, 246, 247,

425

248, 309, 311, 312, 346, 349, 350, 389, 390, 393, 493, 515, 516, 517, 519, 520, 597, 598, 599, 601, 631, 713, 732, 734, 783, 784, 805, 827, 900, 903, 953, 972, 977. Cytotoxic, A549, 100 μg/mL 480, 481, 482. Cytotoxic, A549/ATCC 821. Cytotoxic, ACHN 821. Cytotoxic, ACHN, 100 μg/mL 480, 481, 482. Cytotoxic, AGS 25, 26. Cytotoxic, antiproliferative 760. Cytotoxic, B16 64, 950. Cytotoxic, B16-F-10 732, 734. Cytotoxic, Bel7402 478, 493, 631, 713, 900, 903. Cytotoxic, BGC823 805, 900, 903, 977. Cytotoxic, BGC823, 100 μg/mL 513, 525, 531. Cytotoxic, BSC 339, 341. Cytotoxic, BT-549 821. Cytotoxic, BXPC3 5, 6, 11, 443, 444, 596. Cytotoxic, CAKI-1 821. Cytotoxic, causes G1 arrest in cells 646. Cytotoxic, CCRF-CEM 80, 821. Cytotoxic, CCRF-CEM remarkable potency 767, 768, 769. Cytotoxic, CEM 397, 905, 906. Cytotoxic, CHO-K1 8, 9, 14, 31, 717, 737, 738, 846. Cytotoxic, CNE2 672. Cytotoxic, CNS SF295 444. Cytotoxic, Colon205 821. Cytotoxic, Corbett assay, no selective cytotoxic 157, 158. Cytotoxic, CV-1 597, 598, 599, 601. Cytotoxic, DAMB 521. Cytotoxic, different tumour cell lines 605. Cytotoxic, differential inhibition toward repair deficient lines, particularly ret A-recombinationless strains GW801, GW802, GW803 and AB/886 753. Cytotoxic, differentiation-inducing activity to K562 cells into erythroblast 733, 734, 735, 736, 739, 740. Cytotoxic, DLD-1 604, 612, 613. Cytotoxic, DMS273, remarkable potency 767, 768, 769. Cytotoxic, doxorubicin-resistant L1210/Dx 357, 358. Cytotoxic, DU145 5, 6, 11, 443, 444, 821. Cytotoxic, EAC 886, 887, 888.

426

Index 5 Compound Pharmacological Activity Index

Cytotoxic, EKVX 821. Cytotoxic, FADU 596. Cytotoxic, Fem-X 716. Cytotoxic, H460 8, 9, 14, 31, 717, 737, 738, 846. Cytotoxic, H1325 145. Cytotoxic, H2122 145. Cytotoxic, HCC366 145. Cytotoxic, HCT 400, 402, 409, 412, 428, 417, 427. Cytotoxic, HCT cells in p53 dependent manner 424, 425. Cytotoxic, HCT8 713, 805, 900, 903, 950, 977. Cytotoxic, HCT15 516, 517, 519, 520, 821. Cytotoxic, HCT116 61, 62, 68, 79, 80, 99, 101, 133, 134, 325, 328, 332, 333, 334, 352, 363, 366, 367, 368, 370, 371, 372, 373, 374, 375, 385, 386, 434, 435, 604, 612, 613, 614, 615, 616, 617, 782, 793, 794, 795, 821, 858. Cytotoxic, HCT116, pronounced and selective activity 98. Cytotoxic, HEK-293 804, 838. Cytotoxic, HeLa 401, 652, 653, 655, 672, 905, 906. Cytotoxic, HeLa, 100 μg/mL 513, 525, 531. Cytotoxic, HeLa-S3 127, 361. Cytotoxic, HepG2 25, 26, 317, 799, 800, 801, 804. Cytotoxic, HepG2, 100 μg/mL 480, 481, 482. Cytotoxic, HEY 311, 312. Cytotoxic, HL60 61, 181, 186, 478, 631, 821. Cytotoxic, HL60, 100 μg/mL 513, 525, 531. Cytotoxic, HL60, remarkable potency 767, 768, 769. Cytotoxic, HM02 799, 800, 801. Cytotoxic, hmn fibroblast 52, 53, 55, 57. Cytotoxic, HOP-62 821. Cytotoxic, HOP-62, remarkable potency 767, 768, 769. Cytotoxic, HOP-92 821. Cytotoxic, Hs578T 821. Cytotoxic, HT29 8, 9, 14, 31, 34, 35, 36, 37, 68, 114, 137, 152, 154, 155, 246, 247, 248, 292, 309, 343, 344, 389, 390, 393, 597, 598, 599, 601, 717, 732, 734, 737, 737, 738, 783, 784, 821, 827, 846. Cytotoxic, HT29, selective 856. Cytotoxic, HUVEC 804.

Cytotoxic, HUVECs, SI = 300~1000fold in comparison with other cell lines 760. Cytotoxic, IGROV1 821. Cytotoxic, inibitor of EGF-induced malignant transformation of murine epidermal cells 465. Cytotoxic, JurKat 167. Cytotoxic, K562 75, 110, 112, 183, 184, 187, 188, 190, 197, 199, 571, 572, 652, 653, 653, 654, 655, 661, 662, 663, 664, 665, 804, 821. Cytotoxic, K562, 100 μg/mL 513, 525, 531, 480, 481, 482. Cytotoxic, KB 40, 41, 42, 43, 48, 49, 50, 103, 109, 110, 157, 158, 171, 172, 173, 183, 187, 188, 197, 199, 225, 226, 227, 228, 238, 239, 240, 252, 253, 254, 255, 260, 262, 285, 289, 292, 315, 322, 377, 394, 408, 414, 417, 427, 459, 529, 530, 610, 718, 719, 720, 721, 722, 723, 724, 729, 730, 808, 809, 810, 811, 812, 813, 814, 815, 816, 952. Cytotoxic, KM12 821. Cytotoxic, KM20L2 5, 6, 11, 443, 444, 778, 779. Cytotoxic, KYSE30 380, 381. Cytotoxic, KYSE180 652. Cytotoxic, KYSE520 652. Cytotoxic, L1210 38, 40, 41, 42, 43, 44, 45, 46, 48, 49, 50, 51, 52, 53, 55, 56, 63, 72, 73, 109, 110, 163, 171, 173, 237, 238, 239, 240, 252, 253, 254, 255, 259, 260, 261, 262, 284, 285, 339, 357, 357, 358, 358, 379, 394, 408, 437, 438, 490, 529, 530, 600, 696, 718, 719, 720, 721, 722, 723, 724, 729, 730, 731, 735, 826, 829, 830, 939, 940. Cytotoxic, L1210/Dx 357, 358. Cytotoxic, L-428 913, 914. Cytotoxic, L5178Y 161, 645. Cytotoxic, leukemia 221. Cytotoxic, LMM3 500, 501, 502, 503. Cytotoxic, LoVo 103, 311, 312, 610. Cytotoxic, low nmol/L level 859, 860. Cytotoxic, LOX-IMVI 821. Cytotoxic, lymphocytic leukaemia cells 395. Cytotoxic, M14 821. Cytotoxic, MALME-3M 821. Cytotoxic, MCF7 8, 9, 14, 25, 26, 52, 53, 55, 57, 58, 59, 197, 311, 312, 389, 390, 717,

Index 5 Compound Pharmacological Activity Index

737, 767, 768, 769, 799, 800, 801, 804, 821, 846, 849, 950, 953, 968, 969, 970, 972. Cytotoxic, MCF7 estrogen dependent ER+ 414, 416. Cytotoxic, MCF7/ADR-RES 821. Cytotoxic, MCF12 652. Cytotoxic, MDA-MB-231 34, 35, 36, 37, 246, 247, 248, 827. Cytotoxic, MDA-MB-231 estrogen independent ER- 414, 416. Cytotoxic, MDA-MB-231/ATCC 821. Cytotoxic, MDA-MB-435 821. Cytotoxic, MDA-N 821. Cytotoxic, mechanism of action involving DNA double-stranded breakage 365. Cytotoxic, MEL28 114, 137, 152, 154, 155, 309, 515, 597, 598, 599, 601, 783, 784. Cytotoxic, Mia-PaCa-2 307. Cytotoxic, MMOA: - kabiramides are potent cytotoxic, acts via inhibition of actin dynamics 54. Cytotoxic, mode of action: picomolar potency against some tumour cell lines while being only cytostatic in others 24. Cytotoxic, Molt3 913, 914. Cytotoxic, Molt4 821. Cytotoxic, Mono-Mac-6 401. Cytotoxic, MRC-5 414. Cytotoxic, MS-1 857. Cytotoxic, murine and hmn tumour cell lines 338, 340, 345, 351, 354. Cytotoxic, murine and hmn tumour cell lines, IC50 = 1~15 μmol/L 344. Cytotoxic, NAMALWA 913, 914. Cytotoxic, NCI-ADR-Res 24. Cytotoxic, NCI-H23 821. Cytotoxic, NCI-H226 821. Cytotoxic, NCI-H322M 821. Cytotoxic, NCI-H460 5, 6, 11, 414, 443, 444, 604, 612, 613, 778, 779, 821, 849, 968, 969, 977. Cytotoxic, NCI-H522 61, 821. Cytotoxic, NIH3T3 605. Cytotoxic, NSCLC-N6 249, 292, 781, 785, 786, 789, 790. Cytotoxic, number of HTCLs cells 210. Cytotoxic, OVCAR-3 5, 6, 11, 61, 443, 444, 596, 778, 779, 821, 972.

427

Cytotoxic, OVCAR-5 821. Cytotoxic, OVCAR-8 821. Cytotoxic, P388 5, 6, 11, 24, 32, 70, 71, 114, 115, 152, 156, 243, 244, 250, 276, 277, 292, 309, 311, 312, 339, 341, 346, 353, 393, 396, 406, 416, 421, 422, 441, 442, 443, 444, 453, 454, 466, 467, 468, 469, 500, 502, 503, 521, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 597, 598, 599, 601, 622, 623, 625, 626, 627, 628, 722, 723, 724, 732, 734, 761, 761, 778, 779, 783, 784, 817, 818, 831, 868, 869, 882, 883, 883, 911, 912, 948, 952, 953, 964, 349, 350, 631. Cytotoxic, P388 doxorubicin-resistant 292. Cytotoxic, P388, activity is less potent than cephalostatins 1~4 765, 766. Cytotoxic, p53–/– HCT 424, 425. Cytotoxic, p53+/+ HCT 424, 425. Cytotoxic, PANC1 349, 350. Cytotoxic, panel of 3 NSCLC cell lines, all active 145. Cytotoxic, panel of 6 HTCLs, 4 active, 2 inactive [IC50 > 10 μmol/L] 805. Cytotoxic, panel of 6 HTCLs, 5 active, one inactive [IC50 > 10 μmol/L] 977. Cytotoxic, panel of 11 tumour cell lines, selective 793, 794, 795. Cytotoxic, panel of 14 tumour cell lines 343. Cytotoxic, panel of 14 tumour cell lines with strong activities 344. Cytotoxic, panel of 26 hmn tumour cell lines 650. Cytotoxic, panel of hmn tumour cell lines 174. Cytotoxic, panel of hmn tumour cell lines, GI50 < 10–3 μg/mL 778, 779. Cytotoxic, panel of hmn tumours HTCLs, modest 391, 392, 403, 431. Cytotoxic, panel of HTCLs, 6 inactive 806. Cytotoxic, panel of NCI’s 60 cell lines 61. Cytotoxic, panel of NCI’s 60 hmn carcinoma cell lines 65, 66. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines 821. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, mean GI50 = (16.6±9.5)×10–9 mol/L 779.

428

Index 5 Compound Pharmacological Activity Index

Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, mean GI50 = 1.2×10–9 mol/L 761. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, mean GI50 = (21.7±9.9)×10–9 mol/L 778. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, mean GI50 = 4.1×10–9 mol/L 770. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, mean GI50 = 400×10–9 mol/L 772. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, mean GI50 > 1000×10–9 mol/L 773. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, only SNl2kl and CNS U251 GI50 = 10–7~10–8 mol/L 765, 766. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines,mean GI50 = 11.0×10–9 mol/L 771. Cytotoxic, panel of NCI’s 60 tumour cell lines 68, 69. Cytotoxic, panel of NCI’s hmn tumour cell lines, mean IC50 = 10–3~10–6 μg/mL 157, 158, 159. Cytotoxic, panel of NCI’s tumour cell lines 761. Cytotoxic, panel of NCI’s tumour cell lines, GI50 = 0.5 μg/mL 347. Cytotoxic, PC3 821. Cytotoxic, P-glycoprotein over-expressing SW620 Ad300 930. Cytotoxic, potent 34. Cytotoxic, QG56 604, 612, 613, 614, 615, 616, 617. Cytotoxic, Raji 804. Cytotoxic, RPMI8226 821. Cytotoxic, RPMI8226, remarkable potency 767, 768, 769. Cytotoxic, RXF-393 821. Cytotoxic, RXF-393, remarkable potency 767, 768, 769. Cytotoxic, sea urchin Strongylocentrotus eggs 38, 63. Cytotoxic, several cell lines, moderate 839, 840. Cytotoxic, SF268 8, 9, 14, 31, 414, 416, 717, 737, 738, 821, 846, 849, 968, 969, 970. Cytotoxic, SF295 5, 6, 11, 443, 778, 779, 821. Cytotoxic, SF295, remarkable potency 767, 768, 769. Cytotoxic, SF539 821. Cytotoxic, SK-MEL-2 516, 517, 519, 520, 821. Cytotoxic, SK-MEL-5 778, 779, 821. Cytotoxic, SK-MEL-28 393, 821.

Cytotoxic, SK-N-SH 596. Cytotoxic, SK-OV-3 516, 517, 518, 519, 520, 821. Cytotoxic, SN12C 821. Cytotoxic, SNB19 821. Cytotoxic, SNB75 821. Cytotoxic, SR 821. Cytotoxic, SUP-B15 913, 914. Cytotoxic, SW620 821, 930. Cytotoxic, SW620 and P-glycoprotein overexpressing SW620 Ad300 929, 932. Cytotoxic, SW620 and P-glycoprotein overexpressing SW620 Ad300) 931. Cytotoxic, T24 tumour cells, incorporation of [methyl-3H] thymidine 164, 165. Cytotoxic, T47D 821. Cytotoxic, the highest cytotoxicity to ovarian tumour cell line 650. Cytotoxic, THP-1 804, 913, 914. Cytotoxic, three HTCLs 198. Cytotoxic, TK10 821. Cytotoxic, topoisomerase II sensitive CHO cell-line XVS 371, 373. Cytotoxic, tsFT210 631. Cytotoxic, TSU-Pr1 394, 410, 411, 419. Cytotoxic, TSU-Pr1-B1 410, 411, 419. Cytotoxic, TSU-Pr1-B2 410, 411, 419. Cytotoxic, two cell lines 449. Cytotoxic, U251 821. Cytotoxic, U251, remarkable potency 767, 768, 769. Cytotoxic, U373 311, 312, 953. Cytotoxic, U937 913, 914. Cytotoxic, UACC-257 821. Cytotoxic, UACC62 414, 416, 821. Cytotoxic, UO-31 821. Cytotoxic, UT7 653, 654, 661, 662, 663, 664, 665. Cytotoxic, various hmn and murine tumour cell lines 483, 484, 485. Cytotoxic, WHCO1 380, 381, 652. Cytotoxic, WHCO6 380, 381, 652. Cytotoxic, XF498 516, 517, 519. Cytotoxic, XRS-6 332, 363, 364, 365, 366, 367, 368, 400, 427, 428. D Diarrhetic 269. Differential Cytotoxicicy, BR1/XRS-6 400, 402, 409, 417, 427, 428.

Index 5 Compound Pharmacological Activity Index

Dihydrostreptomycin antagonist 323. Disrupts actin cytoskeleton 54. DNA damaging activity 291. DNA damaging activity, yeast-based assay 286, 287, 288. DNA damaging agent 575, 578. DNA intercalator 400, 402, 409, 412, 417, 427, 428. DNA intercalator and cleavage agent 393. DNA polymerase inhibitor 599, 601. DNA synthesis inhibitor 597, 598, 599, 601. DNA-binding affinity, calf thymus DNA 884. DNA-cleaving agent 404. Dose-dependent inhibition of proliferation 400, 402, 409, 412, 417, 427, 428. E E2 production inhibitor, RAW264.7 cells 564, 565, 577. EGF receptor kinase inhibitor 106, 107, 109, 110. EGFR Kinase inhibitor 720. EGFR tyrosine kinase inhibitor 727, 728. Enzyme cofactor, used in treatment of pellagra 233. G G2 specific cell cycle checkpoint inhibitor 938, 951. G-actin polymerization inhibitor, blocking polymerization by plugging ATP site of G-actin 148, 149. Ganglion blocking agent 967. Glutathione synthesis inhibitor 848. Glycogen synthase kinase-3β inhibitor 797. Growth and gporulation inhibitor, Streptomyces sp. 85E 748, 749, 750, 755. Growth inhibitor, phytoplankton microalga Heterosigma akashiwo 889. H Hepatotoxin 848. HER2 tyrosine kinase inhibitor 725, 726, 728. Herbicidal 118. Herbicide 326, 327. Highly promising drug candidate 533. HIV-1 integrase inhibitor 819. Hypnotic 486.

429

I IC100 263, 264, 265. Ichthyotoxic 149, 229, 243, 699. Ichthyotoxin 47, 130, 132, 148, 150, 151, 242, 302, 303, 304, 490, 698, 700. Ichthyotoxin, common goldfish Carassius auratus 133. IL-6 inhibitor 964. Immune system activity, IL-8 release enhancer 731, 733, 735. Immunoregulator 599, 602, 604. Immunostimulant 649. Immunosuppressant 102, 119, 156, 289, 406, 407, 416, 421. Immunosuppressant, mixed lymphocyte reaction assay 103. Immunosuppressive 209, 295. Immunosuppressive, mixed lymphocyte reaction assay 207, 208. Inducer of erythroid differentiation, hmn leukaemia cells 955, 957. Induces apoptosis, transformed mammalian cells 653, 654, 661, 662, 663, 664, 665. Induces apoptosis, via PARP cleavage 423. Induces Ca2+ release from sarcoplasmic reticulum 340. Inhibitors of variety of kinases, EGFR, kinase c-erbB-2 and tyrosine kinase VEGFR2 720. inhibits binding of radiolabeled colchicine to purified tubulin 119, 120. Inhibits calcineurin 346. Inhibits cell division, fertilized sea urchin eggs 885. Inhibits growth of A549 521. Inhibits Her-2/Neu protooncogene, selectively 720. inhibits induction of VCAM inactive 295. Inhibits induction of VCAM-1, it may be useful for treating coronary artery diseases, angina and noncardiovascular inflammatory diseases 295. Inhibits oxidative phosphorylation through targeting cytochrome bc1 complex resulting in blocking of mitochondrial ATP synthesis 24. Inhibits sperm fertilizing ability, showed weak cytostatic and membranolytic effects 324.

430

Index 5 Compound Pharmacological Activity Index

Inositol triphosphate Ins[1, 4, 5]P3 receptor antagonist 301. Insecticidal 911. Insecticidal, Aphis gossypii, Plutella xylostella, Heliothis virescens, Septoria tritici and Uromyces fabae 317. Insecticidal, silkworm larvae 914, 915, 916. Insecticide 39, 149, 296, 450, 912, 958. Insecticide, neonate larvae of polyphagous pest insect Spodoptera littoralis 416, 417. Inversion of configuration at C-7 leads to a drastic activity reduction 675. Iodine transport inhibitor 130, 132. K Kinase c-erbB-2 inhibitor 529. Kinase EGFR inhibitor inactive 718, 719, 721. Kinase HER2 inhibitor 722, 723, 724. Kinase inhibitor, c-Met kinase 653. Kinases inhibitor, CDK5 865, 960, 961. Kinases inhibitor, CK1δ 865, 960, 961. Kinases inhibitor, GSK3β 865, 960, 961. L Larval metamorphosis inhibitor 670. LC50 417. LD mus ip 854. LD50 brine shrimp 470, 471, 472, 619. LD50 brine shrimp Artemia salina 229. LD50 mosquito fish Gambusia affinis 229. LD50 mus ipr 147, 297, 339. LD50 mus orl 486. Less activity than Lissoclinamide 4 by two orders of magnitude 165. Lipid peroxidation inhibitor 23. Lipogenesis inhibitor 971. LPS-induced NO production inhibitor, RAW264.7 cells 564, 565, 577. M Mammalian protein synthesis inhibitor 96. MDR activity, antifungal, Candida albicans sensitive GU4 strain 894, 895, 897, 898, 899, 903, 971. MDR activity, antifungal, Candida albicans resistant GU5 strain 894, 895, 897, 898, 899, 903, 971. MDR reversing activity, adriamycin -induced resistance of MCF7/Adr 198.

MDR reversing activity, adriamycin-induced resistance of K562/A02 198. MDR reversing activity, vincristine-induced resistance of KB/VCR 198. Mechanism of action involving DNA double-stranded breakage 363, 366, 367, 368. Mechanism of action is inhibition of cyclindependent kinase CDK 882, 883. Medium immunomodulatory activity 783, 784. Molluscacidal, marine snail Biomphalaria glabrata 124. Molluscacidal, snail vector Biomphalaria glabrata 117. Morphogenesis inducer, algae 258. Most active pyridoacridine alkaloids 393. Most potent inhibitor in meridianins 503. Most potent PK inhibitor in meridianins 500. Multidrug resistance reversing agents 864, 907. Mycotoxin 893. Mydriatic agent 967. N Na/K-ATPase inhibitor 632, 633, 636, 637, 638, 639. Natural metamorphosis inducer, larvae of Halocynthia roretzi 667. Negative regulator of insulin signal transduction 751. Nematocide 958. Nephrotoxin 893. Nervous system activity, acetylcholinesterase inhibitor, MMOA: - mixed-competitive inhibition 780. Neuroactive 138, 139, 140, 141, 142. Neuronal differentiation inducer 387, 394, 413, 418. Neuropharmacological agent 153. Neuroprotective, efficiently preventing glutamic acid-caused neuronal cell death 180. Neurotoxicity, rat neurons, inhibitable with NMDA receptor antagonists 3 133. Neurotoxin 232. Neurotoxin, shellfish, implicated in occurrences of neurotoxic poisoning 855. Neurotoxin, to rise to neurotoxin shellfish poisoning in New Zealand oysters 854.

Index 5 Compound Pharmacological Activity Index

Ni Chelating agent 412. NO production inhibitor 746, 747. NO production inhibitor, LPS-stimulated BV2 monoglial cells 922, 923. Novel mycobacterial enzyme mycothiol S-conjugate amidase inhibitor 97. Nucleic acid-cleaving activity 791, 792. O One of the strongest neurotoxin, analgetic, local anesthetic, antispasmotic 292. Osmoprotective 509. Osteoclast differentiation inhibitor 875. Osteoporosis inhibitor 964. Osteoporosis inhibitor, suppresses decreases in bone weight and strength in ovariectomized mice 962. P Papain inhibitor 191. PDE inhibitor 512, 283, 284. Peptidase CPP32 inhibitor 346. PGE2 inhibitor 746, 747. Phycotoxin 967. Phytotoxic, johnsongrass 753. Pigment, ultraviolet sunscreen 874. PK inhibitor inactive, CDK1/cyclin B 505. PK inhibitor inactive, CDK5/p25 505. PK inhibitor inactive, CK1 502. PK inhibitor inactive, GSK3-β 505. PK inhibitor inactive, PKA 505. PK inhibitor inactive, PKG 499, 505. PK inhibitor, cAMP-dependent PK 503. PK inhibitor, Casein kinase 1 503. PK inhibitor, Casein kinase 2 503. PK inhibitor, CDK1/cyclin B 499, 500, 501, 502, 503, 504. PK inhibitor, CDK2/cyclin A 503. PK inhibitor, CDK2/cyclin E 503. PK inhibitor, CDK4/cyclin D1 503. PK inhibitor, CDK5/p25 499, 500, 501, 502, 503, 504. PK inhibitor, cGMP-dependent PK 503. PK inhibitor, c-Jun N-terminal kinase 503. PK inhibitor, CK1 500, 501. PK inhibitor, c-Raf 503. PK inhibitor, Erk1 503. PK inhibitor, Erk2 503. PK inhibitor, GSK3-α 503.

431

PK inhibitor, GSK3-β 499, 500, 501, 502, 503, 504. PK inhibitor, insulin receptor tyrosine kinase 503. PK inhibitor, MAPKK 503. PK inhibitor, PKA 499, 500, 501, 502, 504. PK inhibitor, PKG 500, 501, 502, 504. PK inhibitor, protein kinase Cα 503. PK inhibitor, protein kinase Cβ1 503. PK inhibitor, protein kinase Cβ2 503. PK inhibitor, protein kinase Cγ 503. PK inhibitor, protein kinase Cδ 503. PK inhibitor, protein kinase Cε 503. PK inhibitor, protein kinase Cη 503. PK inhibitor, protein kinase Cξ 503. PKC inhibitor inactive 718, 719, 721. PKC inhibitor 148, 720. Poison of DNA topoisomerase I 905, 906. PPDK inhibitor, non-selective 93. Promotes larvae settlement and metamorphosis in ascidian Ciona savignyi 668, 669. Protease BACE inhibitor 929, 931, 932, 933. Protein phosphatase inhibitor 395. Protein synthesis inhibitor 597, 598, 599, 601. PTP1B inhibitor 268, 751. R Red pigment 741. Reverses of multidrug resistance in cells transfected, breast cancer resistance protein 634. RNA polymerase inhibitor 597, 598, 599, 601. RNA synthesis inhibitor 597, 598, 599, 601. S Sedative, long duration 486. Selective anti-protozoal, chloroquinesusceptible Plasmodium falciparum, selective 337. Selective anti-protozoal, CRPF 336, 339. Selective anti-protozoal, CRPF, selective 337. Selective anti-protozoal, CSPF 336, 339. Selective inhibiting CDK1 and CDK2 over CDK4 and CDK7 883. Selective serotonin uptake inhibitor, serotonin receptor 5-HT2B 879, 880, 881. Serine protease factor Xia inhibitor 86, 87, 88. Serine protease inhibitor 476, 878. Serine threonine phosphatase inhibitor 522. Shellfish toxin 269.

432

Index 5 Compound Pharmacological Activity Index

Siderophore 115. Siderophore, chromazurol S assay, ironchelating properties were confirmed by positive reaction 25, 26. Somatostatin inhibitor 299. Spawning-inducing factor, Asterias sp. 658. Spongicide 47. Stimulator of plant growth 651. Strong affinity to benzodiazepine binding sites of GABAA receptors 401. Sulfatase inhibitor 801.

Toxic, highly toxic to mice 136. Toxic, inhibits cell division in fertilized sea urchin egg 448. Toxic, sea urchins 39. Toxic, teratogen 647. Toxin 148, 271, 272, 273, 820. Tremorgenic mycotoxin 634. Tyrosine kinase inhibitor, inhibit signaling pathway 828, 850, 851, 852. Tyrosine kinase p56lck inhibitor 847. Tyrosine kinase VEGFR2 inhibitor 718, 719, 721.

T Telomerase inhibitor 924, 925, 926, 927, 928. Testosterone 5α-reductase inhibitor 577. To prevent cell proliferation and induce cell apoptosis 499. Topoisomerase I inhibitor 369, 713. Topoisomerase II inhibitor 365, 368, 371, 373, 376, 388, 398, 400, 402, 409, 417, 427, 428. Topoisomerase II inhibitor decatenrtion inhibition assay 337, 363, 366, 367. Topoisomerase II inhibitor inactive, decatenrtion inhibition assay 332, 364, 378. Topoisomerase II inhibitor inactive, inhibits catalytic activity of topoisomerase II 389, 390. Topoisomerase II inhibitor, catenates DNA 420. Topoisomerase inhibitor 386, 437, 438. Toxic, brine shrimp 118, 119, 121, 457, 458, 470, 471, 472, 619, 660. Toxic, brine shrimp Artemia salina 133, 845, 889. Toxic, brine shrimp lethality 417, 416. Toxic, freshwater rotifer Brachionus calyciflorus 169.

U UV-A absorbing activity 876. UV-protective activity 885, 886, 887, 888.

(The End of HAMNP Volume 4)

V Vasodilator 298, 299, 300, 301, 305, 306. Vitamin 644. X Xanthine oxidase inhibitor 498. Z Zebrafish phenotype-based assay, caused a phenotype in zebrafish embryos 388. α α-Adrenoreceptor blocker 460. α-Glucosidase inhibitor 281, 871, 872, 873. β β-Adrenoceptor agonist 146. β-Glucanase inhibitor 463.