Handbook of Active Marine Natural Products: Volume 8 Peptides and Others 9783110655834, 9783110654028

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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 : 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) ----

Jiaju Zhou

Handbook of Active Marine Natural Products Volume 8: Peptides and Others

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

ISBN 978-3-11-065402-8 e-ISBN (PDF) 978-3-11-065583-4 e-ISBN (EPUB) 978-3-11-065413-4 Library of Congress Control Number: 2019941348 Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at http://dnb.dnb.de. © 2019 Walter de Gruyter GmbH, Berlin/Boston Typesetting: Integra Software Services Pvt. Ltd. Printing and binding: CPI books GmbH, Leck Cover image: Science Photo Library/Douwma, Georgette www.degruyter.com

Preface The English edition Handbook of Active Marine Natural Products (HAMNP) with 8 Volumes is a selective version of the Marine Natural Products Dataset. The whole dataset was collected and developed by the Molecular Design Group, Institute of Process Engineering, Chinese Academy of Sciences during 1998–2016. Totally, it covers 19,722 entries of secondary metabolites from marine living things, where 8,350 compound entries have pharmacological activity data. The 8,350 compound entries were arranged into eight volumes to form the set of handbooks as follows: Volume 1: Terpenoids, Part 1 Volume 2: Terpenoids, Part 2 Volume 3: Alkaloids, Part 1 Volume 4: Alkaloids, Part 2 Volume 5: Polyketides and Steroids Volume 6: Aliphatic Metabolites Volume 7: O-Heterocycles and Aromatics Volume 8: Peptides and Others This set of eight HAMNP books gathers the structure, origin, and bioactivity, as well as other relevant information, of 8,350 active marine natural products from 3,025 marine organisms. The HAMNP handbooks represent a largest collection of active secondary metabolites from marine organisms, and all kinds of scientific data have been reorganized as well-formatted data so that the books became helpful to researchers as a convenient reference. The materials covered in these books include those through systematic collection up to 2012, and further accompanied with the latest data published in several core journals until 2016. The work covered in these HAMNP books was accomplished in two phases. The initial phase ranged from 1998 to 2001 and the main phase from 2011 to 2018. In the original version of the dataset, more than 22,000 compounds have been collected, including duplicated compounds from different authors. The comprehensive data compilation process include data specification definition, cross-validation, assessment confirmation, identification of duplicated structures, and merging of relevant information, leading to the final accomplishment of the current 19,722 datasets. In brief, the main compilation process of the HAMNP books is given as follows. First, collect the name list, origin, and structure of chemical compounds from successive annual reviews (see Core References R01 and R02 in Introduction) and literature reviews. Second, double-check the documents to verify and complete other information. Third, confirm the structural information and other types of data using orthogonal information from other sources with cross-validation methods. Fourth, the structures of more than 22,000 compounds are rechecked and the information is integrated by manual identification and computer programs. Finally, the comprehensive information https://doi.org/10.1515/9783110655834-201

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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 handbook. 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 XXIII List of Cancer Cell Codes XXXIII 1

Peptides 1 1.1 Diketopiperazines (dipeptide anhydrides) 1 1.2 Dipeptides 42 1.3 Aeruginosins 45 1.4 Tripeptides 52 1.5 Linear Oligopeptides (4–10 residues) 60 1.6 Linear Polypeptides 87 1.7 Simple Cyclic Peptides 97 1.8 Cyclic Peptides with Oxazole 161 1.9 Cyclic Peptides with Oxazole and Thiazole 163 1.10 Cyclic Peptides with Thiazole 176 1.11 Enniatins 187 1.12 Anabaenopeptins 187 1.13 Destruxins 195 1.14 Simple Cyclic Depsipeptides 196 1.15 Cyclic Lipodepsipeptides 297 1.16 Cyclic Depsipeptides with Thiazole 324 1.17 Cyclic Depsipeptides with Oxazole and Thiazole 336 1.18 Cyclic Depsipeptides with AHP 337 1.19 Depsipeptides with Pyridazine 354 1.20 Monocyclic β-Lactams 356 1.21 Lipopeptides 356 1.22 Lipopeptides with Thiazole 364

2

Others 2.1 2.2 2.3 2.4

365 Aminoacids 365 Carbohydrates 375 Nucleosides 380 S-contaning Compounds

385

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2.5 2.6

As-contaning compounds Miscellaneous 427

426

Index 1 Compound Name and Synonym Index 429 Index 2 Compound Molecular Formula Index 442 Index 3 Compound Organism Source Index 464 Index 4 Compound Sampling Geographic Locality Index 471 Index 5 Compound Pharmacological Activity Index 475

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/10.1515/9783110655834-202

Introduction The Handbook of Active Marine Natural Products covers eight volumes. This book is Volume 8: – Peptides and Others, which includes 1,032 active compounds. Format of Compound Entry. A compound entry starts with a title line, which has two items: the compound’s unique code (from 1 to 1,032 for volume 8) and the main name. The following seven items form the title line as a body, and the graphic structure is placed at the end: Title line (code number, main name) A. Synonyms of the compound (if any) B. Structural type C. Formula (relative molecular mass) D. Physicochemical properties E. Marine source(s) F. Pharmacological data (if any) G. Reference(s) Graphic structure Chemical Names and A. Synonyms. Generally, a compound may have one scientific name and several trivial names. In the handbooks, based on original articles, we select one name as the “main name.” The main name appeared at the title line of each compound entry. In most cases, a trivial name was selected as the main name, and in some cases, the main name is a scientific name. Any synonyms, if any, are presented after the title line as an item of the entry body. B. Structural Type. Structural type is the second item, ordered by the contents order. F. Normalization of Pharmacological Data. All of 1,032 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 the atomic bond level, including complicated glycosides, with stereochemical information based on the data in the original papers. For example, the structure with full stereochemistry of compound 452 marthiapeptide A is

https://doi.org/10.1515/9783110655834-203

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O

S S

O

N S

H N

N

N

O N

NH

NH

S

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

Source Terms The source data of compound 452 marthiapeptide A is Source: Marine-derived bacterium Marinactinospora thermotolerans SCSIO 00652 (deep sea, sediment, South China Sea). 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.

Pharmacological Terms The pharmacological terms in the handbooks are presented in a multilayered structure. In the top layer, there are more than 20 types of most important pharmacological activity terms.They are cytotoxic (in vitro anticancer), antineoplastic (in vivo anticancer), antibacterial, antifungal, antiviral, anti-HIV, anti-inflammatory, antioxidant, antimalarial, NO 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 452 marthiapeptide A, a set of multiple biodata is presented as follows: Pharm: Antibacterial (Micrococcus luteus, MIC = 2.0 μg/mL, control erythromycin, MIC < 1.0 μg/mL, control kanamycin, MIC = 32.0 μg/mL; Staphylococcus aureus

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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)

ATCC 29213, MIC = 8.0 μg/mL, erythromycin, MIC = 16.0 μg/mL, kanamycin, MIC = 8.0 μg/mL; Bacillus subtilis ATCC 6633, MIC = 4.0 μg/mL, erythromycin, MIC < 1.0 μg/mL, kanamycin, MIC < 1.0 μg/mL; Bacillus thuringiensis, MIC = 2.0 μg/mL, erythromycin, MIC < 1.0 μg/mL, kanamycin, MIC = 4.0 μg/mL; Aeromonas hydrophila subsp. hydrophila ATCC7966, MIC > 128.0 μg/mL, erythromycin, MIC = 4.0 μg/mL, kanamycin, MIC < 1.0 μg/mL; Escherichia coli ATCC 25922, MIC > 128.0 μg/mL, erythromycin, MIC = 32.0 μg/mL, kanamycin, MIC = 16.0 μg/mL; Escherichia coli DH5α, MIC > 128.0 μg/mL, erythromycin, MIC = 64.0 μg/mL, kanamycin, MIC = 32.0 μg/mL); cytotoxic (SRB method, SF268, IC50 = (0.38 ± 0.02) μmol/L, control cisplatin, IC50 = (4.76 ± 0.27) μmol/L; MCF7, IC50 = (0.43 ± 0.005) μmol/L, cisplatin, IC50 = (3.99 ± 0.13) μmol/L; NCI-H460, IC50 = (0.47 ± 0.003) μmol/L, cisplatin, IC50 = (2.91 ± 0.18) μmol/L; HepG2, IC50 = (0.52 ± 0.01) μmol/L, cisplatin, IC50 = (2.45 ± 0.07) μmol/L).

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The format is as follows: Pharm: Term name 1 (formatted detail information) Term name 2 (formatted detail information) Under the term name Cytotoxic, a set of multiple cytotoxic biodata is presented as follows: cytotoxic (SRB method, SF268, IC50 = (0.38 ± 0.02) μmol/L, control cisplatin, IC50 = (4.76 ± 0.27) μmol/L; MCF7, IC50 = (0.43 ± 0.005) μmol/L, cisplatin, IC50 = (3.99 ± 0.13) μmol/L; NCI-H460, IC50 = (0.47 ± 0.003) μmol/L, cisplatin, IC50 = (2.91 ± 0.18) μmol/L; HepG2, IC50 = (0.52 ± 0.01) μmol/L, cisplatin, IC50 = (2.45 ± 0.07) μmol/L). The format is as follows: Term name (in vitro/in vivo, target cancer cell 1, quantitative data, positive quantitative data; target cancer cell 2, quantitative data, positive quantitative data; target cancer cell 3, quantitative data, positive quantitative data; target cancer cell 4, quantitative data, positive quantitative data; brief description of related mechanism if any).

control Compound, control’s control Compound, control’s control Compound, control’s control Compound, control’s

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 normalized expressions of almost all the pharmacological data presented in the books. For complete information in volume 8, of all 832 normalized pharmacological activity terms, please see “Index 5 Compound Pharmacological Activity Index.” In summary, these handbooks with eight volumes provide an integrated collection of 8,350 marine natural products chemical components isolated from 3,025 marine organisms and a large amount of pharmacological activity data of these components. It might be used not only as a handbook to look for structures and bioactivities of marine natural products and marine organisms source information, but also as a fundamental platform for studying the marine natural products with a systematic and integrative approach.

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

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9

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

Core References (Guiding References 5) R01

R02

R03 R04 R05

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 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 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 CRC Press, Dictionary of Natural Products on DVD, version 20.2, 2012 Jean-Michel Kornprobst, Encyclopedia of Marine Natural Products, Vol. 1–Vol. 3, 2nd Edition, WILEY BLACKWELL, Germany, 2014

(Dictionaries 17) R06 R07 R08 R09 R10 R11 R12

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

Introduction

R13 R14 R15 R16 R17 R18 R19 R20 R21 R22

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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 Scientific Terms Laboratory of Science Press, English-Chinese Dictionary of Chemistry and Chemical Engineering, 4th Edition, Science Press, Beijing, 2000 Scientific Terms Laboratory of Science Press, English-Chinese Dictionary of Chemistry and Chemical Engineering, 5th Edition, Science Press, Beijing, 2016 Jian Zhuge and Zheng-Xiang Wang, Modern English-Chinese Dictionary of Biotechnology, Science Press, Beijing, 2003 Jing-Ying Tan, English-Chinese Biological Dictionary of Biochemistry and Molecular Biology, 2nd Edition, Science Press, Beijing, 2007 Scientific Terms Laboratory of Science Press, English-Chinese Biological Dictionary, 2nd Edition, Science Press, Beijing, 1997 Scientific Terms Laboratory of Science Press, Chinese-English Biological Dictionary, 2nd Edition, Science Press, Beijing, 1998 Yu Hui, A New Century Chinese-English Dictionary, Foreign Language Teaching and Research Press, Beijing, 2003 Zong-Guo Huang and Mei-Ling Jin, Dictionary of Marine Biology, Ocean Press, Beijing, 1994 (in Chinese) Wenbao Chang, et al., Dictionary of Chemistry, Science Press, Beijing, 2008 (in Chinese)

(Book References 11) R23

R24

R25 R26 R27 R28 R29 R30 R31 R32

R33

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) 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 Janet S. Dodd, The ACS Style Guide, A Manual for Authors and Editors, 2nd Edition, American Chemical Society, Washington, DC, 1997 Shu-Xian Ren, Invertebrates, 2 volumes, Peking University Press, Beijing, 1990 (in Chinese) R. Mcneill Alexander, (translated by Lan-zhi Du), The invertebrates, Chemical Industry Press, Beijing, 2013 (in Chinese) Yanghua Yi and Binghua Jiao, Modern Marine pharmacology, Science Press, Beijing, 2006 (in Chinese) Chang-Yun Wang and Chang-Lun Shao, Marine pharmacology, Science Press, Beijing, 2011 (in Chinese) Rensheng Xu, et al., Chemistry of Natural Products, 2nd Edition, Science Press, Beijing, 2004 (in Chinese) Yue-Zeng Chen, General Biology, Higher Education Press, Beijing, 1997 (in Chinese) 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 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, by using computer’s powerful functions, we have a new way to learn systematical, complete knowledge. In short, a study process in the new way is to search and learn some relationships. Next, we discuss concretely how to use the HAMNP books. In these books, there are three kinds of data and three pairs of important relations. Three kinds of data are (1) marine living sources (source); (2) secondary metabolites (compounds); and (3) pharmacological activities (pharm-activity). The three pairs of important relations are (1) relationship between source and compounds; (2) relationship between compounds and pharm-activity; and (3) relationship between source and pharm-activity. In the case of asking questions, each relation has two directions; hence, together there are six types of questions: Type 1: from known source to unknown compound Type 2: from known compound to unknown source Type 3: from known compound to unknown pharm-activity Type 4: from known pharm-activity to unknown compound Type 5: from known source to unknown pharm-activity Type 6: from known pharm-activity to unknown source (Figure 1) 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 peptides (1–856) are isolated from ascidian of genus Lissoclinum? From index 3 of volume 8, one will get the following related data in detail: Lissoclinum bistratum 410, 411, 412, 413, 414, 415, 416, 417. Lissoclinum cf. badium 959, 960, 961, 962, 963, 964, 965, 966, 967, 968, 968. Lissoclinum japonicum 918, 931. https://doi.org/10.1515/9783110655834-204

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How to Use the HAMNP Books

Lissoclinum patella 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 455, 456, 458, 459, 461, 462. Lissoclinum perforatum 969, 970. Lissoclinum sp. 460, 971, 975, 1017. Lissoclinum vareau 997. Since the question is about peptides, related data are as follows: Lissoclinum bistratum 410, 411, 412, 413, 414, 415, 416, 417. Lissoclinum patella 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 455, 456, 458, 459, 461, 462. Lissoclinum sp. 460, 971. The answer of the current is that 28 peptides compounds (410–417, 424–436, 455, 456, 458–462) are isolated from ascidian of genus Lissoclinum. Then, readers can enjoy studying these 28 peptides compounds by reading the book, including their pharm-activity (question of types 3 and 5). For example, with entry 426, a reader will know that the compound 426 Patellamide A had already been isolated from ascidian Lissoclinum patella and has cytotoxic activities (L1210, IC50 = 2–4 μg/mL; KB, IC50 = 3000 ng/mL); selective cytotoxicity (Corbett assay, zone differential 100 μmol/L); PAF-induced platelet aggregation inhibitor; antibacterial; LD50 (mus, ipr) = 500–1500 mg/kg. Ref: G. W. Kirby, et al, JCS Perkin 1, 1980, 119│ S. S. Afiyatullov, et al, Chem. Nat. Compd. (Engl. Transl.), 2005, 41, 236│X. Li, et al, J. Antibiot., 2006, 59, 248│Y. Sun, et al, JNP, 2011, 75, 111 S

O

5a

6

N

OH

N

H O

S

OH

11

11 Bis(dethio)-10a-methylthio-3a-deoxy-3,3a-didehydrogliotoxin Type: Diketopiperazines. C14H16N2O3S White solid, [α]D25 = −4.6° (c = 0.03, MeOH). Source: Deep-sea fungus Penicillium sp. strain JMF034 (sediments of Suruga Bay, Japan). Pharm: Cytotoxic (P388, IC50 = 3.40 μmol/L); inhibitor of histone methyltransferase (HMT) G9A (IC50 > 100 μmol/L). Ref: Y. Sun, et al, JNP, 2011, 75, 111 S HO

O

N

H

N O

12 Brevianamide F Type: Diketopiperazines. C16H17N3O2 Source: Deep-sea fungus Aspergillus westerdijkiae DFFSCS013 (South China Sea). Pharm: Antifoulant (Bugula neritina larval settlement, EC50 = 6.35 μg/mL, LC50 > 200 μg/mL, LC50/EC50 > 31.5). Ref: X. Zhang, et al, J. Ind. Microbiol. Biotechnol., 2014, 41, 741 O N

H N H N H

O

1.1 Diketopiperazines (dipeptide anhydrides)

5

13 Brevianamide K Type: Diketopiperazines. C21H21N3O2 Yellow needles, mp 157–158 °C. Source: Marinederived fungi Aspergillus versicolor from brown alga Sargassum thunbergii (Pingtan I., Fujian, China) and Aspergillus versicolor, deep-sea fungus Aspergillus versicolor CXCTD-06-6a. Pharm: Antibacterial (30 μg/disk: Escherichia coli, IZD = 7 mm, control Chloramphenicol, IZD = 32 mm; Staphylococcus aureus, IZD = 7 mm, Chloramphenicol, IZD = 31 mm); toxic (brine shrimp Artemia salina, 30 μg/disk, Lethal Rate = 30.9%). Ref: G. -Y. Li, et al, Org. Lett., 2009, 11, 3714│F. -P. Miao, et al, Mar. Drugs, 2012, 10, 131│X. Kong, et al, J. Ocean. Univ. China, 2014, 13, 691 O N HN

N H

O

14 Brevianamide S Type: Diketopiperazines. C42H40N6O4 Source: Marine-derived fungus Aspergillus versicolor (sediment, Bohai Sea, China). Pharm: Antibacterial (Bacille Calmette-Guérin (BCG) of Mycobacterium bovis, selective, used as a live attenuated vaccine against tuberculosis); antituberculosis (potential). Ref: F. Song, et al, Org. Lett., 2012, 14, 4770│F. -P. Miao, et al, Mar. Drugs, 2012, 10, 131 O HN

N HN

O O

NH NH

N O

15 Brevianamide W Diketopiperazine V Type: Diketopiperazines. C21H23N3O2 Source: Deep-sea fungus Aspergillus versicolor CXCTD-06-6a. Pharm: Antioxidant (DPPH radical scavenger, moderate). Ref: X. Kong, et al, J. Ocean Univ. China, 2014, 13, 691 O HN

N R

HN O

H

6

1 Peptides

16 Bromobenzisoxazolone barettin Type: Diketopiperazines. C24H23Br2N7O5 Brownish-yellow solid, mp 150–151 °C, [α]D25 = +0.01° (c = 0.01,MeOH). Source: Sponge Geodia barretti. Pharm: Inhibits settlement of barnacle larvae Balanus improvises. Ref: M. Sjögren, et al, JNP, 2004, 67, 368│E. Hedner, et al, JNP, 2008, 71, 330 O O N H

Br OH O

Br

NH HN

N H

O

H N

NH2 NH

17 Chrysogenazine Type: Diketopiperazines. C19H21N3O2 Source: Mangrove-derived fungus Penicillium chrysogenum from mangrove Porteresia coarctata (leaves, Chorao I., Goa, India). Pharm: Antibacterial. Ref: P. Devi, et al, Indian J. Microbiol., 2012, 52, 617

O

H N N

O

N H

18 Cristatumin A Type: Diketopiperazines. C19H21N3O3 Source: Marine-derived fungus Eurotium cristatum EN-220 from brown alga Sargassum thunbergii (location unspecified). Pharm: Antibacterial (Escherichia coli, MIC = 64.8 μg/mL). Ref: F. -Y. Du, et al, Bioorg. Med. Chem. Lett., 2012, 22, 4650

O

H N

N H

N H

OH O

1.1 Diketopiperazines (dipeptide anhydrides)

7

19 Cristatumin B Type: Diketopiperazines. C29H37N3O3 Source: Marine-derived fungus Eurotium cristatum EN-220 from brown alga Sargassum thunbergii (location unspecified). Pharm: Toxic (brine shrimp Artemia salina bioassay, LC50 = 74.4 μg/mL). Ref: F. -Y. Du, et al, Bioorg. Med. Chem. Lett., 2012, 22, 4650

O

H N

N H

OH O

N H

20 Cristatumin F Type: Diketopiperazines. C31H43N3O2 Source: Marine-derived fungus Eurotium cristatum EN-220 (endophytic) from brown alga Sargassum thunbergii. Pharm: Antioxidant (radical DPPH scavenger, modest); cytotoxic (marginal cell proliferation inhibition). Ref: X. Zou, et al, Molecules, 2014, 19, 17839

O

H N N H

O

N H

21 Cryptoechinuline D Type: Diketopiperazines. C38H41N3O5 Yellow solid (acetone), mp 158–160 °C. Source: Mangrove-derived fungus Aspergillus effuses H1-1 from unidentified mangrove (rhizosphere soil, Fujian, China). Pharm: Cytotoxic (P388, IC50 = 3.43 μmol/L, control Doxorubicin, IC50 = 0.33 μmol/L; HL60, IC50 > 100 μmol/L, Doxorubicin, IC50 = 0.05 μmol/L; Bel7402, IC50 > 100 μmol/L, Doxorubicin, IC50 = 0.24 μmol/L; A549, IC50 > 100 μmol/L, Doxorubicin, IC50 = 0.08 μmol/L). Ref: H. Gao, et al, Arch. Pharmacal Res., 2013, 36, 952

8

1 Peptides

O H N 31

12

N H N H

28

O O HO

H OH

22 (−)-Cryptoechinuline D Type: Diketopiperazines. C38H41N3O5 [α]D20 = −199.7° (c = 0.15, MeOH). Source: Mangrove-derived fungus Aspergillus effuses H1-1 from unidentified mangrove (rhizosphere soil, Fujian, China), terrestrial fungus Aspergillus amstelodam. Pharm: Cytotoxic (P388, IC50 = 11.3 μmol/L, control Doxorubicin, IC50 = 0.33 μmol/L; HL60, IC50 > 100 μmol/L, Doxorubicin, IC50 = 0.05 μmol/L; Bel7402, IC50 > 100 μmol/L, Doxorubicin, IC50 = 0.24 μmol/L; A549, IC50 > 100 μmol/L, Doxorubicin, IC50 = 0.08 μmol/L). Ref: G. Gatti, et al, J. Chem. Soc., Chem. Commun., 1976, 435│ H. Gao, et al, Arch. Pharmacal Res., 2013, 36, 952 O H N 31R

12S

N H N H

28R

O O HO

H

(12S,28R,31R)

OH

23 (+)-Cryptoechinuline D Type: Diketopiperazines. C38H41N3O5 [α]D20 = +210.3° (c = 0.15, MeOH). Source: Mangrove-derived fungus Aspergillus effuses H1-1 from unidentified mangrove (rhizosphere soil, Fujian, China). Pharm: Cytotoxic (P388, IC50 = 2.50 μmol/L, control Doxorubicin, IC50 = 0.33 μmol/L; HL60, IC50 > 100 μmol/L, Doxorubicin, IC50 = 0.05 μmol/L; Bel7402, IC50 > 100 μmol/L, Doxorubicin, IC50 = 0.24 μmol/L; A549, IC50 > 100 μmol/L, Doxorubicin, IC50 = 0.08 μmol/L). Ref: H. Gao, et al, Arch. Pharmacal Res., 2013, 36, 952

1.1 Diketopiperazines (dipeptide anhydrides)

9

O H N 31S

12R

N H

28S

N H

O O HO

H

(12R,28S,31S)

OH

24 Cyclo(2-hydroxy-Pro-R-Leu) Type: Diketopiperazines. C11H18N2O3 Colorless oil, [α]D20 = +40° (c = 0.05, MeOH). Source: Marine-derived streptomycete Streptomyces sp. (sediment, Bohai Bay, China). Pharm: Cytotoxic (HL60, IC50 = 98.49 μmol/L). Ref: B. Li, et al, J. Asian Nat. Prod. Res., 2011, 13, 1146 O OH NH N O

25 Cyclo-(4-S-hydroxy-R-proline-R-isoleucine) Type: Diketopiperazines. C11H18N2O3 Colourless oil, [α]D21 = +12° (c = 0.025, CHCl3). Source: Sponge Stelletta sp. (Jamieson Reef, Bonaparte Archipelago, Australia). Pharm: Cytotoxic (SF268, GI50 > 295 μmol/L; MCF7, GI50 = 204 μmol/L; H460, GI50 = 234 μmol/L; HT29, GI50 = 270 μmol/L; CHO-K1, GI50 > 295 μmol/L). Ref: S. P. B. Ovenden, et al, Mar. Drugs, 2011, 9, 2469

H

O NH

HO

N O

26 (3S,7R,8aS)-Cyclo(4-hydroxyprolylleucyl) Type: Diketopiperazines. C11H18N2O3 mp 178–179 °C, [α]D28 = −148.2° (c = 1, H2O). Source: An unidentified marine-derived bacterium A108 from zoanthid Palythoa sp. Pharm: Plant growth regulator. Ref: J. M. Cronan, et al, Nat. Prod. Lett., 1998, 11, 271

10

1 Peptides

O

H HO

7

8a

HN

N 3

O

27 Cyclo(4-hydroxy-S-Pro-S-Trp) Type: Diketopiperazines. C16H17N3O3 Colorless needles, [α]D20 = −139° (c = 0.10, MeOH). Source: Marine-derived streptomycete Streptomyces sp. (sediment, Bohai Bay, China). Pharm: Cytotoxic (HL60, IC50 = 64.34 μmol/L). Ref: B. Li, et al, J. Asian Nat. Prod. Res., 2011, 13, 1146

H

O NH

HO

H N

N O

H

28 Cyclo-(D-cis-Hyp-L-Phe) Type: Diketopiperazines. C14H16N2O3 [α]D24 = +34.7° (c = 1.02, MeOH). Source: Marine-derived fungus Aureobasidium pullulans from an unidentified sponge (Okinawa); marine-derived bacterium Pseudoalteromonas luteoviolacea from brown alga Padina australis (surface, Hawaii). Pharm: Stimulates antibiotic production. Ref: H. Shigemori, et al, JNP, 1998, 61, 696│Z. Jiang, et al, Nat. Prod. Lett., 2000, 14, 435 O N HN

OH

O

29 Cyclo(L-Ile-L-Pro) Type: Diketopiperazines. C11H18N2O2 Source: Deep-sea fungus Aspergillus versicolor ZBY-3. Pharm: Cytotoxic (K562, 100 μg/mL). Ref: Y. Dong, et al, Mar. Drugs, 2014, 12, 4326

H

O NH

N O

H

1.1 Diketopiperazines (dipeptide anhydrides)

11

30 Cyclo(leucylprolyl) Cyclo(L-Leu-L-Pro) Type: Diketopiperazines. C11H18N2O2 Cryst., mp 168–172 °C, mp 158–159 °C, [α]D21 = −144° (c = 0.5, H2O). Source: Sponges Calyx cf. podatypa and Tedania ignis, deep-sea fungus Aspergillus versicolor ZBY-3, terrestrial fungi (Aspergillus ochraceus, Streptomyces gancidicus, Candida albicans, Guignardia laricina and Ceratocystis spp.). Pharm: Cytotoxic (K562, 100 μg/mL); antifungal; phytotoxin (associated with fungal diseases of trees). Ref: F. J. Schmidtz, et al, JOC, 1983, 48, 3941│S. D. Bull,et al, JCS Perkin 1, 1998, 2313│DNP on DVD, 2012, version 20.2│Y. Dong, et al, Mar. Drugs, 2014, 12, 4326

H

O NH

8aS

N

3S

O

31 (3S,8αS)-Cyclo(prolylvalyl) Type: Diketopiperazines. C10H16N2O2 Needles (butanol), mp 189.5 °C, mp 169–172 °C, [α]D20 = −157° (c = 1, CHCl3), [α]D20 = −180.5° (c = 1, EtOH). Source: Green alga Scenedesmus sp., sponges Tedania ignis (Caribbean Sea) and Calyx cf. podatypa (Caribbean Sea), terrestrial fungi (Rhizoctonia solani and Rosellinia necatrix). Pharm: Antibiotic; phytotoxic. Ref: F. J. Schmidtz, et al, JOC, 1983, 48, 3941│CRC Press, DNP on DVD, 2012, version 20.2 O 3S

N 8aS

HN O

H

32 Cyclo(D-Pro-D-Phe) Type: Diketopiperazines. C14H16N2O2 Source: Deep-sea fungus Aspergillus versicolor ZBY-3. Pharm: Cytotoxic (K562, 100 μg/mL). Ref: Y. Dong, et al, Mar. Drugs, 2014, 12, 4326

H

O NH

N O

H

12

1 Peptides

33 Cyclo(D-Tyr-D-Pro) Type: Diketopiperazines. C14H16N2O3 Source: Deep-sea fungus Aspergillus versicolor ZBY-3. Pharm: Cytotoxic (K562, 100 μg/mL). Ref: Y. Dong, et al, Mar. Drugs, 2014, 12, 4326

H

O N

HN

HO

O

H

34 12-Demethyl-12-oxo-eurotechinulin B (6Z)-6-{[2-(1,1-Dimethylprop-2-en-1-yl)-5,7-bis(3-methylbut-2-en-1-yl)-1H-indol-3-yl] methylene}piperazine-2,3,5-trione Type: Diketopiperazines. C28H33N3O3 Colorless amorphous powder, [α]D25 = −12.5° (c = 0.08, MeOH). Source: Mangrove-derived fungus Eurotium rubrum from semimangrove Hibiscus tiliaceus (Hainan, China). Pharm: Cytotoxic (SMMC-7721, IC50 = 30 μg/mL). Ref: H. -J. Yan, et al, Helv. Chim. Acta, 2012, 95, 163

O

H N

O

N H

O

N H

35 Deoxybisdethiobis(methylthio)gliotoxin Type: Diketopiperazines. C15H20N2O3S2 Oil, [α]D = −48° (c = 0.3, MeOH). Source: Marine-derived fungus Pseudallescheria sp. MFB165 from brown alga Agarum cribrosum (Korea waters). Pharm: Antibacterial. Ref: X. F. Li, et al, J. Antibiot., 2006, 59, 248 S N H OH

O N S

O

36 Deoxymycelianamide Type: Diketopiperazines. C22H28N2O3 Amorph. powder (MeOH), [α]D20 = −150° (c = 0.1, MeOH). Source: Marine-derived fungus Gliocladium sp. (sea mud, Rushan, China); marine-derived fungus Gliocladium sp. YUP08 (from sediment-borne, China).

1.1 Diketopiperazines (dipeptide anhydrides)

13

Pharm: Cytotoxic (A375-S2); cytotoxic (MTT assay 72 h, HL60, IC50 = 2.02 μmol/L, control Vincristin, IC50 = 2.46 μmol/L; U937, IC50 = 0.79 μmol/L, Vincristin, IC50 = 1.61 μmol/L; T47D, IC50 = 30.51 μmol/L, Vincristin, IC50 = 12.57 μmol/L). Ref: Y. F. Huang, et al, J. Asian Nat. Prod. Res., 2007, 9, 197│Y. Yao, et al, Pharmazie, 2009, 64, 616

O

H N N H

O

O

37 Didehydroechinulin B Type: Diketopiperazines. C29H37N3O2 Source: Marine- derived fungus Penicillium griseofulvum from a deep ocean sediment, mangrove-derived fungus Aspergillus effuses H1-1 from unidentified mangrove (rhizosphere soil, Fujian, China). Pharm: Cytotoxic (P388, IC50 > 100 μmol/L, control Doxorubicin, IC50 = 0.33 μmol/L; HL60, IC50 = 15.6 μmol/L, Doxorubicin, IC50 = 0.05 μmol/L; Bel7402, IC50 = 4.2 μmol/L, Doxorubicin, IC50 = 0.24 μmol/L; A549, IC50 = 1.43 μmol/L, Doxorubicin, IC50 = 0.08 μmol/L). Ref: L. N. Zhou, et al, Helvetica Chimica Acta, 2010, 93, 1888│ H. Gao, et al, Arch. Pharmacal Res., 2013, 36, 952 O

H N N H

N H

O

38 8,9-Dihydrobarettin Type: Diketopiperazines. C17H21BrN6O2 Brownish solid, [α]D21 = −24° (c = 0.096, MeOH). Source: Sponge Geodia barretti (psychrophilic, cold water, Kosterfjord, Northern Swedish West coast and Sula Ridge, Norway). Pharm: Inhibits settlement of barnacle larvae Balanus improvises (EC50 = 7.9 μmol/L); reduces recruitment (0.1% in paint, barnacle Balanus improvisus by 67% and mussel Mytilus edulis by 72%, having potential as a non-toxic alternative to heavy-metal-based antifoulant paints); selective serotonin-receptor (exclusively targeting 5-HT2C receptor). Ref: Sölter, S. et al, Tet. Lett., 2002, 43, 3385│M. Sjögren, et al, JNP, 2004, 67, 368│ E. Hedner, et al, JNP, 2006, 69, 1421│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)│ E. Hedner, et al, JNP, 2008, 71, 330

14

1 Peptides

O 8

9

NH Br

H N

HN

N H

O

NH2 NH

39 Dihydrocarneamide A Type: Diketopiperazines. C26H31N3O3 Source: Marine-derived fungus Paecilomyces variotii EN-291 (endophytic). Pharm: Cytotoxic (NCI-H460, IC50 = 69.3 μmol/L). Ref: P. Zhang, et al, Chin. Chem. Lett., 2015, 26, 313 O

N

H N H

H O

N H

O

40 Dihydrocryptoechinulin D Type: Diketopiperazines. C38H43N3O5 Source: Mangrove-derived fungus Aspergillus effuses H1-1 (from mangrove rhizosphere soil, Fujian, China). Pharm: Topoisomerase inhibitor (selective, moderate). Ref: H. Gao, et al, Org. Biomol. Chem., 2012, 10, 9501 O

H N N H

N H

O O HO

H OH

41 Dihydroneochinulin B Type: Diketopiperazines. C19H21N3O2 Colorless needles (acetone), mp 213–214 °C, [α]D20 = −59.8° (c = 0.085, MeOH). Source: Mangrove-derived fungus Aspergillus effuses H1-1 from unidentified mangrove (rhizosphere soil, Fujian, China). Pharm: Cytotoxic (P388, IC50 > 100 μmol/L, control Doxorubicin, IC50 = 0.33 μmol/L; HL60, IC50 > 100 μmol/L, Doxorubicin, IC50 = 0.05 μmol/L; Bel7402, IC50 = 55.1 μmol/L, Doxorubicin, IC50 = 0.24 μmol/L; A549, IC50 = 30.5 μmol/L, Doxorubicin, IC50 = 0.08 μmol/L). Ref: H. Gao, et al, Arch. Pharmacal Res., 2013, 36, 952

1.1 Diketopiperazines (dipeptide anhydrides)

15

O H N N H N H

O

42 12,13-Dihydroxyfumitremorgin C Type: Diketopiperazines. C22H25N3O5 Yellow cryst., mp 197–198 °C, [α]D = +18.4°. Source: Marine-derived fungus Aspergillus sydowi PFW1-13 (from driftwood sample, China). Pharm: Tremorgenic mycotoxin. Ref: M. Zhang, et al, JNP, 2008, 71, 985 OH O OH N O

N

N H H

O

H

43 8,9-Dihydroxyisospirotryprostatin A Type: Diketopiperazines. C22H25N3O6 Pale yellow solid, [α]D20 = +147.2° (c = 0.1, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from sea cucumber Stichopus japonicus (China waters). Pharm: Cytotoxic (MTT assay, HL60, IC50 = 125.3 μmol/L, control VP-16, IC50 = 0.083 μmol/L; SRB assay, A549, inactive). Ref: F. Wang, et al, Tetrahedron, 2008, 64, 7986

O

H N

HO

2

OH 8

O N

9

N O

O

H

44 Diketopiperazine dimer Type: Diketopiperazines. C34H39N5O4 Source: Sponge Spongosorites sp. Pharm: Sortase A (SrtA) inhibitor (in Staphylococcus aureus, low). Ref: K. -B. Oh, et al, BoMCL, 2005, 15, 4927

16

1 Peptides

H

O

H

H N

N H O

O NH

H N N H

H

O

H

45 9ξ-O-2(2,3-Dimethylbut-3-enyl)brevianamide Q Type: Diketopiperazines. C27H33N3O3 Colorless crystals, mp 89–92 °C, [α]D24 = −16.0° (c = 0.11, CHCl3). Source: Marine-derived fungus Aspergillus versicolor from brown alga Sargassum thunbergii (Pingtan I., Fujian, China). Pharm: Antibacterial (30 μg/disk: Escherichia coli, IZD = 7 mm, control Chloramphenicol, IZD = 32 mm; Staphylococcus aureus, IZD = 7 mm, Chloramphenicol, IZD = 31 mm); toxic (brine shrimp Artemia salina, 30 μg/disk, Lethal Rate = 43.2%). Ref: F. Song, et al, Org. Lett., 2012, 14, 4770│F. -P. Miao, et al, Mar. Drugs, 2012, 10, 131

O HN

N HN O

O

46 Dysamide A Type: Diketopiperazines. C14H20Cl6N2O2 Prisms (Me2CO/petrol), mp 118–119 °C, [α]D = −36.6° (c = 0.265, MeOH). Source: Sponge Dysidea fragilis, Zoanthid Zoanthus sp. Pharm: Osteoporotic agent. Ref: J. Y. Su, et al,JNP, 1993, 56, 637

Cl

Cl N

Cl O

O Cl

N Cl

Cl

47 Etzionin Type: Diketopiperazines. C26H42N4O4 Foaming oil. Source: Ascidian Didemnum rodriguesi. Pharm: Cytotoxic; antifungal. Ref: S. Hirsch, et al, Tet. Lett., 1989, 30, 4291│E. Vaz, et al, Tetrahedron: Asymmetry, 2003, 14, 1935

1.1 Diketopiperazines (dipeptide anhydrides)

17

OH N

O

N

O

O N H

NH2

48 Gliocladride Type: Diketopiperazines. C22H30N2O3 Source: Marine-derived fungus Gliocladium sp. (sediment-borne, China). Pharm: Cytotoxic (A375-S2, IC50 = 3.86 μg/mL, control Vincristin, IC50 = 1.22 μg/mL). Ref: Y. Yao,et al Pharmazie, 2007, 62, 478 O

H N N H

O

O

49 Gliocladride A Type: Diketopiperazines. C22H28N2O4 White solid, [α]D20 = −150° (c = 0.05, MeOH). Source: Marine-derived fungus Gliocladium sp. (sea mud, Rushan, China). Pharm: Cytotoxic (MTT assay 72 h, HL60, IC50 = 17.87 μmol/L, control Vincristin, IC50 = 2.46 μmol/L; U937, IC50 = 12.80 μmol/L, Vincristin, IC50 = 1.61 μmol/L; T47D, IC50 = 42.80 μmol/L, Vincristin, IC50 = 12.57 μmol/L). Ref: Y. Yao, et al, Pharmazie, 2009, 64, 616

O

H N N

O

O

OH

50 Gliocladride B Type: Diketopiperazines. C22H28N2O4 White solid, [α]D20 = −66° (c = 0.05, MeOH). Source: Marine-derived fungus Gliocladium sp. (sea mud, Rushan, China). Pharm: Cytotoxic (MTT assay 72 h, HL60, IC50 = 19.86 μmol/L, control Vincristin, IC50 = 2.46 μmol/L; U937, IC50 = 11.60 μmol/L, Vincristin, IC50 = 1.61 μmol/L; T47D, IC50 = 52.83 μmol/L, Vincristin, IC50 = 12.57 μmol/L). Ref: Y. Yao, et al, Pharmazie, 2009, 64, 616

O

H N N OH

O

O

18

1 Peptides

51 Golmaenone Type: Diketopiperazines. C19H21N3O4 Yellow cryst. (CHCl3), mp 160–161 °C, [α]D = +7.1° (c = 0.4, CHCl3). Source: Marine-derived fungus Aspergillus sp. (cultured broth). Pharm: Antioxidant (DPPH scavenger, IC50 = 20 μmol/L, control Ascorbic acid, IC50 = 20 μmol/L); UV-A (320–390 nm) protecting activity (ED50 = 90 μmol/L, control Oxybenzone, ED50 = 350 μmol/L). Ref: Li, Y. et al, CPB, 2004, 52, 375│ M. Saleem, et al, NPR, 2007, 24, 1142 (rev) O O

HN NH O

NH O

52 2′ξ-Hydroxy-fumitremorgin B Δ3′-Isomer (1) Type: Diketopiperazines. C27H33N3O6 Cryst., [α]D20 = +15° (c = 0.1, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from sea cucumber Stichopus japonicus (China waters). Pharm: Cytotoxic (MTT assay: Molt4, IC50 = 11.0 μmol/L, HL60, IC50 = 5.4 μmol/L; SRB assay: A549, IC50 = 11.6 μmol/L, Bel7402, IC50 = 10.8 μmol/L; control VP-16: MTT assay: Molt4, IC50 = 0.003 μmol/L, HL60, IC50 = 0.083 μmol/L; SRB assay: A549, IC50 = 1.400 μmol/L, Bel7402, IC50 = 1.025 μmol/L). Ref: Wang, F. et al, Tetrahedron, 2008, 64, 7986 OH O OH

O

N HO

N

N

2'

O 3'

H

isomer 1

53 2′ξ-Hydroxy-fumitremorgin B Δ3′-Isomer (2) Type: Diketopiperazines. C27H33N3O6 Pale yellow powder, [α]D20 = −5.7° (c = 0.1, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from sea cucumber Stichopus japonicus (China waters). Pharm: Cytotoxic (MTT assay: Molt4, IC50 = 11.0 μmol/L, HL60, IC50 = 3.4 μmol/L; SRB assay: A549, IC50 = 11.0 μmol/L, Bel7402, IC50 = 7.0 μmol/L; control VP-16: MTT assay: Molt4, IC50 = 0.003 μmol/L, HL60, IC50 = 0.083 μmol/L; SRB assay: A549, IC50 = 1.400 μmol/L, Bel7402, IC50 = 1.025 μmol/L). Ref: Wang, F. et al, Tetrahedron, 2008, 64, 7986

1.1 Diketopiperazines (dipeptide anhydrides)

OH O

OH

19

O N

HO

N

N 2'

O 3'

H

isomer 2

54 9-Hydroxyfumitremorgin C Type: Diketopiperazines. C22H25N3O4 Source: Marine-derived fungus Aspergillus fumigatus (intertidal mud, Yingkou, Liaoning, China). Pharm: Cytotoxic (U937 cells inhibitor, moderate). Ref: Y. Wang, et al, Chem. Biodiversity, 2012, 9, 385

OH

O

O N

N

N H H

O

H

55 9-Hydroxyfumitremorgin C Type: Diketopiperazines. C22H25N3O5 Source: Marine-Derived Fungus Aspergillus fumigatus YK-7. Pharm: Cytotoxic (U937). Ref: Y. Wang, et al, Chem. Biodiversity, 2012, 9, 385 OH O

OH

O N

N H

N O

H

56 14-Hydroxyterezine D Type: Diketopiperazines. C19H23N3O3 Pale yellow powder, [α]D22 = +17.8° (c = 0.13, MeOH). Source: Marine-derived fungus Aspergillus sydowi PFW1-13 (driftwood sample, China). Pharm: Cytotoxic (MTT bioassay, A549, IC50 = 7.31 μmol/L; HL60, IC50 = 9.71 μmol/L). Ref: M. Zhang, et al, JNP, 2008, 71, 985

20

1 Peptides

O HO

N

14

N O

N H

57 (Indole-N-isoprenyl)-tryptophan-valine Type: Diketopiperazines. C21H27N3O2 Source: Marine fungus M-3 (Ascomycota phylum). Pharm: Antifungal (Pyricularia oryzae, strong and selective). Ref: H. -G. Byun, et al, J. Antibiot., 2003, 56, 102 O

H N N H

O

N

58 Indotertine B Type: Diketopiperazines. C33H45N3O3 Source: Marine-derived streptomycete Streptomyces sp. CHQ-64. Pharm: Cytotoxic (HCT8, IC50 = 6.96 μmol/L, A549, IC50 = 4.88 μmol/L); Ref: Q. Che, et al, Org. Lett., 2012, 14, 3438│Q. Che, et al, JNP, 2013, 76, 759

O

H H N H

H N

H

O

O N

59 Mactanamide Type: Diketopiperazines. C19H20N2O4 Cryst. (MeOH), mp 241–243 °C, [α]D = −42,8° (c = 0.93, MeOH). Source: Marine-derived fungus Aspergillus sp. from brown alga

1.1 Diketopiperazines (dipeptide anhydrides)

21

Sargassum sp. (Philippines). Pharm: Antifungal. Ref: P. Lorenz, et al, Nat. Prod. Lett., 1998, 12, 55 O NH HO N O HO

60 6-Methoxyspirotryprostatin B 8,9-Dehydrotryprostatin A Type: Diketopiperazines. C22H23N3O4 Pale yellow powder, [α]D21 = −47.7° (c = 0.26, CHCl3). Source: Marine-derived fungus Aspergillus sydowi PFW1-13 (driftwood sample, China). Pharm: Cell cycle inhibitor (mammalian); cytotoxic (MTT assay, A549, IC50 = 8.29 μmol/L; HL60, IC50 = 9.71 μmol/L). Ref: M. Zhang, et al, JNP, 2008, 71, 985 O

O HN

N

8 9

1

12

N O

H

O

61 Notoamide C Type: Diketopiperazines. C26H31N3O4 [α]D27 = +23° (c = 0.25, MeOH). Source: Marinederived fungus Aspergillus sp. from mussel Mytilus edulis. Pharm: Cytotoxic ( HeLa and L1210, IC50 = 22–52 μg/mL); induces G2/M-cell cycle arrest (6.3 μg/mL,cell line not specified); Antifoulant (significant); antilarval settlement (Bugula neritina, strong). Ref: H. Kato, et al, Angew. Chem., Int. Ed., 2007, 46, 2254; 2013, 52, 7909 (corrigendum)│M. Chen, et al, JNP, 2013, 76, 547; 1229 (corrigendum)│S. Li, et al, JACS, 2012, 134, 788135│X. -Y. Zhang, et al, J. Ind. Microbiol. Biotechnol., 2014, 41, 741

N

O

17 3S

N H

H O

O

N H

H O

22

1 Peptides

62 Notoamide D Type: Diketopiperazines. C26H31N3O4 [α]D27 = −163° (c = 0.32, MeOH). Source: Marine-derived fungus Aspergillus sp. from mussel Mytilus edulis. Pharm: Cytotoxic ( HeLa and L1210, IC50 = 22–52 μg/mL). Ref: H. Kato, et al, Angew. Chem. Int. Ed. Engl., 2007, 46, 2254; 2013, 52, 7909 (corrigendum).

H

HO

O 11S

N 17

N O

N H

O

H

63 Okaramine S Type: Diketopiperazines. C32H36N4O3 Source: Mangrove-derived fungus Aspergillus taichungensis ZHN-7-07 from mangrove Acrostichum aureum. Pharm: Cytotoxic (HL60, IC50 = 0.78 μmol/L, K562, IC50 = 22.4 μmol/L). Ref: S. Cai, et al, Tetrahedron, 2015, 71, 3715

HN OH

H O

N H N H

O

N H

64 Otoamide C Type: Diketopiperazines. C26H31N3O4 Source: Deep-sea fungus Aspergillus westerdijkiae DFFSCS013 (South China Sea). Pharm: Antifoulant (Bugula neritina larval settlement, EC50 = 9.85 μg/mL, LC50 > 200 μg/mL, LC50/EC50 > 20.3). Ref: X. Zhang, et al, J. Ind. Microbiol. Biotechnol., 2014, 41, 741

1.1 Diketopiperazines (dipeptide anhydrides)

O

N

H

H

N H O O

23

O

N H

65 18-Oxotryprostatin A Type: Diketopiperazines. C22H25N3O4 Amorph. yellow powder, [α]D21 = −31.5° (c = 0.14, CHCl3). Source: Marine-derived fungus Aspergillus sydowi PFW1-13 (driftwood sample, China). Pharm: Cytotoxic (MTT bioassay, A549, IC50 = 1.28 μmol/L). Ref: M. Zhang, et al, JNP, 2008, 71, 985 O

H

HN N H

O

O O 18

N H

66 13-Oxoverruculogen Type: Diketopiperazines. C27H31N3O7 Cryst., [α]D20 = +83.8° (c = 0.1, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from sea cucumber Stichopus japonicus (China waters). Pharm: Cytotoxic (MTT assay: Molt4, IC50 = 25.7 μmol/L, HL60, IC50 = 1.9 μmol/L; SRB assay: A549, IC50 = 16.9 μmol/L, Bel7402, IC50 = 25.6 μmol/L; control VP-16: MTT assay: Molt4, IC50 = 0.003 μmol/L, HL60, IC50 = 0.083 μmol/L; SRB assay: A549, IC50 = 1.400 μmol/L, Bel7402, IC50 = 1.025 μmol/L). Ref: F. Wang, et al, Tetrahedron, 2008, 64, 7986 O

OH

O N

13

O

N

N H O

O

8

H

O

67 Penicibrocazine B Type: Diketopiperazines. C19H22N2O5S Source: Marine-derived fungus Penicillium brocae MA-231 (endophytic). Pharm: Antibacterial (Staphylococcus aureus, MIC = 32.0 μg/mL);

24

1 Peptides

antifungal (Gaeumannomyces graminis, MIC = 0.25 μg/mL). Ref: L. H. Meng, et al, Mar. Drugs, 2015, 13, 276

S

H

N OH

OH

N

H O

O

H H

O

68 Penicibrocazine C Type: Diketopiperazines. C20H26N2O6S2 Source: Marine-derived fungus Penicillium brocae MA-231 (endophytic). Pharm: Antibacterial (Staphylococcus aureus, MIC = 0.25 μg/mL). Ref: L. H. Meng, et al, Mar. Drugs, 2015, 13, 276 OH

H S

H

N OH

OH

N

H O

O

S H

OH

69 Penicibrocazine D Type: Diketopiperazines. C20H26N2O6S2 Source: Marine-derived fungus Penicillium brocae MA-231 (endophytic). Pharm: Antibacterial (Staphylococcus aureus, MIC = 8.0 μg/mL); antifungal (Gaeumannomyces graminis, MIC = 8.0 μg/mL). Ref: L. H. Meng, et al, Mar. Drugs, 2015, 13, 276 O

H S

H

N OH

OH

N

H O

O

S H

O

70 Penicibrocazine E Type: Diketopiperazines. C20H24N2O6S2 Source: Marine-derived fungus Penicillium brocae MA-231 (endophytic). Pharm: Antifungal (Gaeumannomyces graminis, MIC = 0.25 μg/mL). Ref: L. H. Meng, et al, Mar. Drugs, 2015, 13, 276

1.1 Diketopiperazines (dipeptide anhydrides)

O

H S

OH

N

H O

O H

N OH

25

S H

O

71 Phomazine B Type: Diketopiperazines. C20H22N2O3S2 Source: Mangrove-derived fungus Phoma sp. OUCMDZ-1847 (endophytic). Pharm: Cytotoxic (HL60, HCT116, K562, MGC-803 and A549, IC50 between 8.5 μmol/L and > 10 μmol/L). Ref: F. Kong, et al, JNP, 2014, 77, 132

S N H OH

O

O NH

S

72 Prenylcyclotryprostatin B Type: Diketopiperazines. C28H35N3O5 Source: Marine-derived fungus Aspergillus fumigatus (intertidal mud, Yingkou, Liaoning, China). Pharm: Cytotoxic (U937 cells inhibitor, moderate). Ref: Y. Wang, et al, Chem. Biodiversity, 2012, 9, 385 O O

OH

O N

S

N

S

N O

H

73 13-O-Prenyl-26-hydroxyverruculogen Type: Diketopiperazines. C32H41N3O8 Source: Marine-derived fungus Penicillium brefeldianum SD-273. Pharm: Toxic (brine shrimp Artemia salina bioassay, LC50 = 9.44 μmol/L). Ref: C. -Y. An, et al, Mar. Drugs, 2014, 12, 746

26

1 Peptides

O N

O HO N O

H O OH

N O O

74 Rodriguesine A Type: Diketopiperazines. C26H42N4O3 Glassy solid. Source: Ascidian Didemnum sp. (Bahia State, Brazil). Pharm: Antibacterial (mixture of Rodriguesine A and Rodriguesine B: Staphylococcus aureus ATCC 6538, MIC = 62.5 μg/mL; Staphylococcus aureus ATCC259223, MIC = 22.6 μg/mL; ORSA 8, MIC = 45.3 μg/mL; ORSA 108, MIC = 91.0 μg/mL; Escherichia coli ATCCNTCC861, MIC = 125.0 μg/mL; Escherichia coli ATCC259222, MIC = 45.6 μg/mL; Pseudomonas aeruginosa ATCC27853, MIC = 22.6 μg/mL; Pseudomonas aeruginosa 13, MIC = 45.3 μg/mL; Pseudomonas aeruginosa P1, MIC = 4.3 μg/mL; Enterococcus faecalis ATCC14506, MIC = 125.0 μg/mL; Streptococcus sanguinis ATCC15300, MIC = 125.0 μg/mL; Streptococcus sobrinus ATCC27607, MIC = 125.0 μg/mL; Streptococcus mutans UA159, MIC = 62.5 μg/mL; Streptococcus mutans (clinical isolate 2.M7/4), MIC = 31.2 μg/mL); antifungal (mixture ofRodriguesine A and Rodriguesine B, Candida albicans ATCC 36801 (serum type A), MIC = 125.0 μg/mL). Ref: M. H. Kossuga, et al, J. Braz. Chem. Soc., 2009, 20, 704

O

H N

N

O O N H

NH2

75 Rodriguesine B Type: Diketopiperazines. C27H44N4O3 Source: Ascidian Didemnum sp. (Bahia State, Brazil). Pharm: Antibacterial (mixture of Rodriguesine A and Rodriguesine B: Staphylococcus aureus ATCC 6538, MIC = 62.5 μg/mL; Staphylococcus aureus ATCC259223, MIC = 22.6 μg/mL; ORSA 8, MIC = 45.3 μg/mL; ORSA 108, MIC = 91.0 μg/mL; Escherichia coli ATCCNTCC861, MIC = 125.0 μg/mL; Escherichia coli ATCC259222, MIC = 45.6 μg/mL; Pseudomonas aeruginosa ATCC27853, MIC = 22.6 μg/mL; Pseudomonas aeruginosa 13, MIC = 45.3 μg/mL; Pseudomonas aeruginosa P1, MIC = 4.3 μg/mL; Enterococcus faecalis ATCC14506, MIC = 125.0 μg/mL; Streptococcus sanguinis ATCC15300, MIC = 125.0 μg/mL; Streptococcus sobrinus

1.1 Diketopiperazines (dipeptide anhydrides)

27

ATCC27607, MIC = 125.0 μg/mL; Streptococcus mutans UA159, MIC = 62.5 μg/mL; Streptococcus mutans (clinical isolate 2.M7/4), MIC = 31.2 μg/mL); antifungal (mixture of Rodriguesine A and Rodriguesine B, Candida albicans ATCC 36801 (serum type A), MIC = 125.0 μg/mL). Ref: M. H. Kossuga, et al, J. Braz. Chem. Soc., 2009, 20, 704 H N

O

N

O O

NH2 N H

76 Rubrumazine A Type: Diketopiperazines. C25H33N3O4 Source: Mangrove-derived Fungus Eurotium rubrum MA-150. Pharm: Toxic (brine shrimp Artemia salina bioassay, LC50 = 29.8 μmol/L). Ref: L. -H. Meng, et al, JNP, 2015, 78, 909 O

H N

8

N H

O

N H HO O

77 Rubrumazine B Type: Diketopiperazines. C24H31N3O4 Source: Mangrove-derived Fungus Eurotium rubrum MA-150. Pharm: Toxic (brine shrimp Artemia salina bioassay, LC50 = 2.43 μmol/L). Ref: L. -H. Meng, et al, JNP, 2015, 78, 909 O

H N

8

N H

O

N H HO OH

78 Rubrumazine C Type: Diketopiperazines. C24H33N3O4 Source: Mangrove-derived Fungus Eurotium rubrum MA-150. Pharm: Toxic (brine shrimp Artemia salina bioassay, LC50 = 16.5 μmol/L). Ref: L. -H. Meng, et al, JNP, 2015, 78, 909

28

1 Peptides

O

H N

8

HO

N H

OH

O

N H

79 Rubrumline A Type: Diketopiperazines. C24H31N3O4 White powder; [α]D25 = −30.6° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 25.79%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 H O HO

H N O

9

N H

OH

8

4

N H

7

1

80 Rubrumline B Type: Diketopiperazines. C25H33N3O4 White powder; [α]D25 = −58.4° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 15.17%, CC50 > 200 μmol/ L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 H O O

N H

OH

H N O

9 8

4

7

N H

1

81 Rubrumline C Type: Diketopiperazines. C26H33N3O5 White powder; [α]D25 = −70.5° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 2.5%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182

1.1 Diketopiperazines (dipeptide anhydrides)

H O

H N O

9

O 4

29

N H

8

O OH

N H

7

1

82 Rubrumline D Type: Diketopiperazines. C24H29N3O4 White powder; [α]D25 = −2.0° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 52.64%, IC50 = 126 μmol/L, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 H N O

O

9

N H

8

4

HO OH

N H

7

1

83 Rubrumline E Type: Diketopiperazines. C25H31N3O4 White powder; [α]D25 = −38.5° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 5.0%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 H N O

O

9

N H

8

4

HO

O

7

N H

1

84 Rubrumline F Type: Diketopiperazines. C25H35N3O4 White powder; [α]D25 = −22.7° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 5.69%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182

30

1 Peptides

H

H N

O

O

9

N H

4

8

H

HO O

N H

7

1

85 Rubrumline G Type: Diketopiperazines. C26H35N3O5 White powder; [α]D25 = −13.1° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 3.48%, CC50 > 200 μmol/ L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 H

H N

O

O

9

N H

O 4

8

H

O OH

N H

7

1

86 Rubrumline H Type: Diketopiperazines. C24H31N3O4 White powder; [α]D25 = −47.1° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 15.08%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 H

H N

O

O

9

N H

8

4

7

HO OH

N H

1

1.1 Diketopiperazines (dipeptide anhydrides)

31

87 Rubrumline I Type: Diketopiperazines. C25H33N3O4 White powder; [α]D25 = −15.7° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 15.59%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 H

H N

O

O

9

N H

8

4

N H

7

1

HO O

88 Rubrumline J Type: Diketopiperazines. C19H23N3O3 White powder; [α]D25 = −19.2° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 12.99%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 HO

H

H N

O

O

9

N H 4

7

8

H

N H

1

89 Rubrumline K Type: Diketopiperazines. C20H23N3O4 White powder; [α]D25 = 3.5° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 14.29%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182

32

1 Peptides

HO

O

H N

O

O

9

N H

8

4

N H

7

1

90 Rubrumline L Type: Diketopiperazines. C23H27N3O5 Yellow powder; [α]D25 = −5.2° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 6.45%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 O

H N

O HO

O

9

N H

OH

8

4

7

N H

1

91 Rubrumline M Type: Diketopiperazines. C19H23N3O3 White powder; [α]D25 = 11.9° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 3.38%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 H O

H N O

9

N H 4

7

8

H

N H

OH

1

92 Rubrumline N Type: Diketopiperazines. C21H27N3O3 White powder; [α]D25 = 17.3° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 18.29%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182

1.1 Diketopiperazines (dipeptide anhydrides)

H O

H N O

9

N H 4

8

H

N H

7

33

OH

1

93 Rubrumline O Type: Diketopiperazines. C19H23N3O2 White powder; [α]D25 = 4.8° (c = 0.05, MeOH). Source: Mangrove-derived Fungus Eurotium rubrum (endophytic). Pharm: Antiviral (influenza A/WSN/33 virus, 100 μmol/L, InRt = 17.95%, CC50 > 200 μmol/L). Ref: X. Chen, et al, Eur. J. Med. Chem., 2015, 93, 182 H O

H N O

9

N H 4

H

8

N

1

7

94 Shornephine A Type: Diketopiperazines. C25H26N2O5 Source: Marine-derived fungus Aspergillus sp. CMB-M081F (Australia). Pharm: P-Glycoprotein inhibitor (MDR cancer cells). Ref: Z. G. Khalil, et al, JOC, 2014, 79, 8700

H

O

HO

O N N H

O

H

OH

95 Spirotryprostatin A Type: Diketopiperazines. C22H25N3O4 Pale yellow amorph. powder, [α]D26 = −34° (c = 0.10, CHCl3). Source: Marine-derived fungi Aspergillus sydowi PFW1-13 and Aspergillus fumigatus BM939. Pharm: Mammalian cell cycle inhibitor. Ref: C. Cui, et al, Tetrahedron 1996, 52, 12651│H.Wang,et al, JOC, 2000, 65, 4685│M. Zhang, et al, JNP, 2008, 71, 985

34

1 Peptides

O HN

O

H

N

8 9

1

12

N O

H

O

96 Spirotryprostatin B Type: Diketopiperazines. C21H21N3O3 Pale yellow cryst., mp 137–138 °C, [α]D22 = −162.1° (c = 0.92, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus. BM939 Pharm: Mammalian cell cycle inhibitor. Ref: C. Cui, et al, Tetrahedron, 1996, 52, 12651 O

O HN

N

8 9

1

12

N O

H

97 Spirotryprostatin C Type: Diketopiperazines. C27H33N3O6 Pale yellow powder, [α]D20 = −76.5° (c = 0.1, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from sea cucumber Stichopus japonicus (China waters). Pharm: Cytotoxic (MTT assay: Molt4, IC50 = 25.7 μmol/L, HL60, IC50 = 43.5 μmol/L; SRB assay: A549, IC50 = 35.9 μmol/L, Bel7402, IC50 = 68.8 μmol/L; control VP-16: MTT assay: Molt4, IC50 = 0.003 μmol/L, HL60, IC50 = 0.083 μmol/L; SRB assay: A549, IC50 = 1.400 μmol/L, Bel7402, IC50 = 1.025 μmol/L). Ref: C. B. Cui, et al, Tetrahedron, 1996, 52, 12651│C. B. Cui, et al, J. Antibiot., 1996, 49, 832│F. Wang, et al, Tetrahedron, 2008, 64, 7986 O OH N1

O OH

8S

9R

N 12

N O

H

O

98 Spirotryprostatin D Type: Diketopiperazines. C27H33N3O7 Pale yellow powder, [α]D20 = −73.6° (c = 0.1, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from sea cucumber Stichopus japonicus (China waters). Pharm: Cytotoxic (MTT assay: Molt4, IC50 = 25.7 μmol/L, HL60, IC50 = 45.0 μmol/L; SRB assay: A549, IC50 = 35.5 μmol/L,

1.1 Diketopiperazines (dipeptide anhydrides)

35

Bel7402, IC50 = 17.5 μmol/L; control VP-16: MTT assay: Molt4, IC50 = 0.003 μmol/L, HL60, IC50 = 0.083 μmol/L; SRB assay: A549, IC50 = 1.400 μmol/L, Bel7402, IC50 = 1.025 μmol/L). Ref: C. B. Cui, et al, Tetrahedron, 1996, 52, 12651│C. B. Cui, et al, J. Antibiot., 1996, 49, 832│F. Wang, et al, Tetrahedron, 2008, 64, 7986 O OH OH O N1

8S

9R

N 12R

N

OH O O

99 Spirotryprostatin E Type: Diketopiperazines. C27H33N3O8 Pale yellow powder, [α]D20 = −60.9° (c = 0.1, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus from sea cucumber Stichopus japonicus (China waters). Pharm: Cytotoxic (MTT assay: Molt4, IC50 = 3.1 μmol/L, HL60, IC50 = 2.3 μmol/L; SRB assay: A549, IC50 = 3.1 μmol/L, Bel7402, IC50 = 98.4 μmol/L; control VP-16: MTT assay: Molt4, IC50 = 0.003 μmol/L, HL60, IC50 = 0.083 μmol/L; SRB assay: A549, IC50 = 1.400 μmol/L, Bel7402, IC50 = 1.025 μmol/L). Ref: C. B. Cui, et al, Tetrahedron, 1996, 52, 12651│C. B. Cui, et al, J. Antibiot., 1996, 49, 832│F. Wang, et al, Tetrahedron, 2008, 64, 7986

HO

O OH OH O

O N1

8S

9R

N 12

N O

H

O

100 Spirotryprostatin F Type: Diketopiperazines. C22H25N3O6 Source: Marine-derived fungus Aspergillus fumigatus from soft coral Sinularia sp. (Kunashir I., Kuril Is). Pharm: Stimulatory phytoregulatory activity. Ref: F. Wang, et al, Tetrahedron, 2008, 64, 7986│ S. S. Afiyatullov, et al, Chem. Nat. Compd., 2012, 48, 95 O OH OH O N

HN N H O O

H

36

1 Peptides

101 Terezine D Type: Diketopiperazines. C19H23N3O2 Powder, mp 192–104 °C, [α]D = +7° (c = 0.58, MeOH). Source: Marine-derived fungus Aspergillus sydowi PFW1-13 (driftwood sample, China). Pharm: Antifungal. Ref: Y. Wang, et al, JNP, 1995, 58, 93│M. Zhang, et al, JNP, 2008, 71, 985 O HN

14

NH O N H

102 Tryprostatin A Type: Diketopiperazines. C22H27N3O3 Pale yellow cryst., mp 120–123 °C, [α]D27 = −69.7° (c = 0.07, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus BM939 (from sediment). Pharm: Mammalian cell cycle inhibitor (tsFT210, 50 μg/mL, caused complete arrest in G2/M phase); microtubule assembly inhibitor (disruption of microtubule spindle); mycotoxin. Ref: C. B. Cui, et al, J. Antibiot., 1995, 48, 1382; 1996, 49, 527; 534; 832│M. Kondoh,et al, J. Antibiot., 1998, 51, 801│T. Usui, et al, Biochem. J., 1998, 333, 543│S. Zhao, et al, Tetrahedron Let., 1998, 39, 7009 O

H

HN N H

O

N H

O 1''

103 Tryprostatin B Type: Diketopiperazines. C21H25N3O2 Pale yellow cryst., mp 102–105 °C, [α]D27 = −71.1° (c = 0.6, CHCl3). Source: Marine-derived fungus Aspergillus fumigatus BM939 (sediment). Pharm: Mammalian cell cycle inhibitor (tsFT210, 12.5 μg/mL, caused complete arrest in G2/M phase); microtubule assembly inhibitor (disruption of microtubule spindle). Ref: C. B. Cui, et al, J. Antibiot., 1995, 48, 1382; 1996, 49, 527; 534│K. M. Depew, et al, JACS, 1996, 118, 12463│M. Kondoh, et al, J. Antibiot., 1998, 51, 801│T. Usui, et al, Biochem. J., 1998, 333, 543│S. Zhao, et al, Tetrahedron Let., 1998, 39, 7009│J. M. Schkeryantz, et al, JACS, 1999, 121, 11964│T. S. Bugni, et al, NPR, 2004, 21, 143 (rev)

1.1 Diketopiperazines (dipeptide anhydrides)

O

37

H

HN N H

O

N H

104 Variecolorin A Type: Diketopiperazines. C24H30ClN3O3 Source: Marine-derived fungus Aspergillus variecolor (halotolerant). Pharm: Antioxidant (DPPH radical scavenger, weak). Ref: W. -L. Wang, et al, JNP, 2007, 70, 1558 H N Cl

O

O OH

N H

N H

105 Variecolorin B Type: Diketopiperazines. C24H29Cl2N3O2 Source: Marine-derived fungus Aspergillus variecolor (halotolerant). Pharm: Antioxidant (DPPH radical scavenger, weak). Ref: W. -L. Wang, et al, JNP, 2007, 70, 1558 H N Cl

O

O Cl

N H

N H

106 Variecolorin C Type: Diketopiperazines. C24H29N3O3 Source: Marine-derived fungus Aspergillus variecolor (halotolerant). Pharm: Antioxidant (DPPH radical scavenger, weak). Ref: W. -L. Wang, et al, JNP, 2007, 70, 1558

38

1 Peptides

H N O OH

O N H

N H

107 Variecolorin D Type: Diketopiperazines. C27H35N3O4 Source: Marine-derived fungus Aspergillus variecolor (halotolerant). Pharm: Antioxidant (DPPH radical scavenger, weak). Ref: W. -L. Wang, et al, JNP, 2007, 70, 1558 H N OO O

O N H

N H

108 Variecolorin E Type: Diketopiperazines. C24H29N3O3 Source: Marine-derived fungus Aspergillus variecolor (halotolerant). Pharm: Antioxidant (DPPH radical scavenger, weak). Ref: W. -L. Wang, et al, JNP, 2007, 70, 1558 H N O O

O N H

N H

109 Variecolorin F Type: Diketopiperazines. C24H30ClN3O3 Source: Marine-derived fungus Aspergillus variecolor (halotolerant). Pharm: Antioxidant (DPPH radical scavenger, weak). Ref: W. -L. Wang, et al, JNP, 2007, 70, 1558

1.1 Diketopiperazines (dipeptide anhydrides)

39

H N O

O N H

N H

HO

Cl

110 Variecolorin G Type: Diketopiperazines. C24H29N3O2 Amorph. Powder, [α]D25 = −16° (c = 0.1, MeOH). Source: Mangrove-derived fungus Eurotium rubrum from semimangrove Hibiscus tiliaceus (Hainan, China). Pharm: Antioxidant (DPPH radical scavenger, weak); lethal (brine shrimp, LC50 = 42.6 μg/mL). Ref: W. -L. Wang, et al, JNP, 2007, 70, 1558│H. -J. Yan, et al, Helv. Chim. Acta, 2012, 95, 163│F. -Y. Du, et al, BoMCL, 2012, 22, 4650 O NH HN N H

O

111 Variecolorin H Type: Diketopiperazines. C20H23N3O3 Source: Marine-derived fungus Aspergillus variecolor (halotolerant). Pharm: Antioxidant (DPPH radical scavenger, weak). Ref: W. -L. Wang, et al, JNP, 2007, 70, 1558 O

H N

O

O N H

N H

112 Variecolorin I Type: Diketopiperazines. C25H31N3O3 Source: Marine-derived fungus Aspergillus variecolor (halotolerant). Pharm: Antioxidant (DPPH radical scavenger, weak). Ref: W. -L. Wang, et al, JNP, 2007, 70, 1558

40

1 Peptides

O

H N

O

O N H

N H

113 Variecolorin J Type: Diketopiperazines. C23H25N3O3 Source: Marine-derived fungus Aspergillus variecolor (halotolerant). Pharm: Antioxidant (DPPH radical scavenger, weak). Ref: W. -L. Wang, et al, JNP, 2007, 70, 1558 O

H N

O

O N H

N H

114 Variecolorin K Type: Diketopiperazines. C27H35N3O4 Source: Marine-derived fungus Aspergillus variecolor (halotolerant). Pharm: Antioxidant (DPPH radical scavenger, weak). Ref: W. -L. Wang, et al, JNP, 2007, 70, 1558 H N O

O N H

OH

O

N H

115 Variecolorin M (3Z,6S)-3-{{2-(1,1-Dimethylprop-2-en-1-yl)-7-[(2E)-4-hydroxy-3-methylbut-2-en-1-yl]-1Hindol-3-yl}methylidene}-6-methylpiperazine-2,5-dione Type: Diketopiperazines. C24H29N3O3 Yellow amorphous powder, [α]D25 = −36° (c = 0.1, MeOH). Source: Deep-sea fungus Penicillium griseofulvum (sediment). Pharm: Antioxidant (DPPH radical scavenger, IC50 = 135 μmol/L, control Ascorbic acid, IC50 = 26 μmol/L);

1.1 Diketopiperazines (dipeptide anhydrides)

41

cytotoxic inactive (P388, HL60, Bel7402 and A549, IC50 > 50 μmol/L). Ref: L. -N. Zhou, et al, Helvetica Chimica Acta, 2010, 93, 1758 H N O

O N H

N H

HO

116 Variecolorin N (3Z,6S)-3-{{2-(1,1-Dimethylprop-2-en-1-yl)-7-{[3-(hydroxymethyl)-3-methyloxiran-2-yl] methyl}-1H-indol-3-yl}methylidene}-6-methylpiperazine-2,5-dione Type: Diketopiperazines. C24H29N3O4 Yellow amorphous powder, [α]D25 = −58° (c = 0.1, MeOH). Source: Deep-sea fungus Penicillium griseofulvum (sediment). Pharm: Antioxidant (DPPH radical scavenger, IC50 = 120 μmol/L, control Ascorbic acid, IC50 = 26 μmol/L); cytotoxic inactive (P388, HL60, Bel7402 and A549, IC50 > 50 μmol/L). Ref: L. -N. Zhou, et al, Helvetica Chimica Acta, 2010, 93, 1758 H N O

O N H

N H

O

HO

117 Variecolorin O Type: Diketopiperazines. C19H21N3O3 Yellow amorphous powder, [α]D25 = −8.9° (c = 0.1, MeOH). Source: Deep-sea fungus Penicillium griseofulvum (sediment). Pharm: Antioxidant (DPPH radical scavenger, IC50 = 91 μmol/L, control Ascorbic acid, IC50 = 26 μmol/L); cytotoxic inactive (P388, HL60, Bel7402 and A549, IC50 > 50 μmol/L). Ref: L. -N. Zhou, et al, Helvetica Chimica Acta, 2010, 93, 1758 H N

HO O

O N H

N H

42

1 Peptides

118 Verruculogen Type: Diketopiperazines. C27H33N3O7 Plates (C6H6/EtOH), mp 233–235 °C (dec), [α]D = −27.7° (CHCl3). Source: Marine-derived fungus Aspergillus sydowi PFW1-13 (driftwood sample, China), terrestrial fungi (Penicillium spp., Aspergillus caespitosus and Aspergillus fumigatus). Pharm: Cell cycle progression inhibitor; muscle contractant; tremorgenic toxin; LD50 (mus, ipr) = 2.4 mg/kg. Ref: G. W. Kirbyet al, J. Chem. Soc., Perkin Trans. 1 1980, 1, 119│G. W. Kirby, et al, J. Chem. Soc., Perkin Trans.│1 1988, 2, 301│Y. -C. Fang, et al, Acta Cryst. E, 2007, 63, o4788│M. Zhang, et al, JNP, 2008, 71, 985│CRC Press, DNP on DVD, 2012, version 20.2 OH O OH N

13

O

H N O

8

N H

O

H

O

119 Versicamide H Type: Diketopiperazines. C28H29N3O4 Source: Marine-derived Fungus Aspergillus versicolor HDN08-60. Pharm: Cytotoxic (HeLa, IC50 = 19.4 μmol/L; HCT116, IC50 = 17.7 μmol/L; HL60, IC50 = 8.7 μmol/L; K562, IC50 = 22.4 μmol/L). PTK inhibitor. Ref: J. Peng, et al, JOC, 2014, 79, 7895 O

O O

N

N N

O

1.2 Dipeptides 120 Benarthin Type: Dipeptides. C17H25N5O7 Powder +1/2H2O (monohydrochloride), mp 178–180 °C (monohydrochloride), [α]D24 = −2.5° (c = 1, H2O). Source: Marine-derived streptomycetes Streptomyces xanthophaeus and Streptomyces sp. from brown alga Analipus japonicus (Charatsunai beach, Muroran, Japan). Pharm: Siderophore; pyroglutamyl peptidase inhibitor. Ref: T. Aoyagi, et al, J. Antibiot., 1992, 45, 1079; 1084; 1088│ Y. Matsuo, et al, JNP, 2011, 74, 2371

1.2 Dipeptides

43

OH OH O

OH

H

N H

H

OH

O

H

O N H

NH N H

NH2

121 Proximicin A Type: Dipeptides. C12H11N3O6 Amorph. solid. Source: Marine-derived bacterium Verrucosispora maris AB-18-032. Pharm: Cytotoxic (AGS, GI50 = 0.6 μg/mL, TGI > 10 μg/mL; HepG2, GI50 = 0.82 μg/mL, TGI > 10 μg/mL; MCF7, GI50 = 7.2 μg/mL, TGI > 10 μg/mL). Ref: H. -P. Fiedler, et al, J. Antibiot., 2008, 61, 158│K. Schneider, et al, Angew. Chem., Int. Ed., 2008, 47, 3258 H N

O

H N

O

O 1

O

O

NH2

O

122 Proximicin B Type: Dipeptides. C20H19N3O7 Amorph. solid. Source: Marine-derived bacterium Verrucosispora maris AB-18-032. Pharm: Cytotoxic (AGS, GI50 = 1.5 μg/mL, TGI > 10 μg/mL; HepG2, GI50 = 9.5 μg/mL, TGI > 10 μg/mL; MCF7, GI50 = 5.0 μg/mL, TGI > 10 μg/mL); Antibacterial (agar plate diffusion assay, Bacillus subtilis DSM 10, 1.0 mg/mL, IZD = 12 mm; Brevibacillus brevis DSM 30, 0–3 mg/mL, IZD = 12 mm; 1.0 mg/mL, IZD = 22 mm; Staphylococcus aureus DSM 20231, 1.0 mg/mL, IZD = 12 mm). Ref: K. Schneider, et al, Angew. Chem., Int. Ed., 2008, 47, 3258│ H. -P. Fiedler, et al, J. Antibiot., 2008, 61, 158 H N

O O

H N

O O

1

O O

H N OH

123 Proximicin C Type: Dipeptides. C22H20N4O6 Amorph. solid. Source: Marine-derived bacterium Verrucosispora maris AB-18-032. Pharm: Cytotoxic (AGS, GI50 = 0.25 μg/mL, TGI > 10 μg/mL; HepG2, GI50 = 0.78 μg/mL, TGI > 10 μg/mL; MCF7, GI50 = 9.0 μg/mL,

44

1 Peptides

TGI > 10 μg/mL). Ref: K. Schneider, et al, Angew. Chem., Int. Ed., 2008, 47, 3258│ H.-P. Fiedler, et al, J. Antibiot., 2008, 61, 158 H N

O O

H N

O

1

O

O

H N

O

N H

124 Terpeptin Antibiotic RK-F 1010 Type: Dipeptides. C28H40N4O3 Yellow solid, mp 92–95 °C, [α]D = −135.2° (c = 0.1, CHCl3). Source: Mangrove-derived fungus Aspergillus sp. W-6 from mangrove Acanthus ilicifolius (China waters), marine-derived fungus Aspergillus sp. from brown alga Sargassum sp. (Ishigaki I., Okinawa), Aspergillus terreus 95F-1. Pharm: Cytotoxic (A549, IC50 = 15.0 μmol/L); mammalian cell cycle inhibitor; antioxidant (free radical scavenger, to protect N18-RE-105 cells against L-glutamate toxicity, considerably more potent than control a-tocopherol); mammalian cell cycle inhibitor. Ref: T. Kagamizono, et al, Tet. Lett., 1997, 38, 1223│Z. Lin, et al, Magn. Reson. Chem., 2008, 46, 1212│M. Izumikawa, et al, J. Antibiot., 2010, 63, 389 H N

O N

O

N H

O

N H

125 Tunichrome An1 Type: Dipeptides. C26H25N3O11 Source: Ascidian Ascidia nigra. Pharm: Blood pigment which selectively accumulates vanadium. Ref: E. M. Oltz, et al, JACS, 1988, 110, 6162 OH OH

HO O 1'

HO 3'''

HO OH

N H

NH OH

O

3''

NH2

OH OH

1.3 Aeruginosins

45

126 Tunichrome Mm 1 Type: Dipeptides. C19H19N3O6 Source: Ascidian Molgula manhattensis. Pharm: Readily chelates Vanadium. Ref: E. M. Oltz, et al, JACS, 1988, 110, 6162 HO

O OH

N H

HO

NH

O

OH

H 2N

127 Tunichrome Mm 2 Type: Dipeptides. C23H27N3O6 Source: Ascidian Molgula manhattensis. Pharm: Readily chelates Vanadium. Ref: E. M. Oltz, et al, JACS, 1988, 110, 6162 HO

O OH

N H

HO

NH

O

OH

H 2N

128 Virenamide B Type: Dipeptides. C30H38N4O2S Oil, [α]D = −775° (c = 0.1, CHCl3). Source: Ascidian Diplosoma virens. Pharm: Cytotoxic (P388, A549, HT29 and CV-1, all IC50s = 5 μg/mL). Ref: A. R. Carroll, et al, JOC, 1996, 61, 4059│C. J. Moody, et al, JOC, 1999, 64, 8715

O

H N N

S

O

N H

H N

1.3 Aeruginosins 129 Aeruginosin 101 Type: Aeruginosins. C29H44Cl2N6O9S [α]D = −11° (c = 0.5, MeOH aq). Source: Cyanobacterium Microcystis aeruginosa. Pharm: Serine protease inhibitor. Ref: K. Ersmark, et al, Angew. Chem., Int. Ed., 2008, 47, 1202

46

1 Peptides

H

N

O S

O

OH

O

O

H O

H N

N H O

H N

NH NH2

H HO Cl Cl

OH

130 Aeruginosin 102A Type: Aeruginosins. C33H44N6O11S Amorph. powder. Source: Cyanobacterium Microcystis aeruginosa NEIS 102. Pharm: Thrombin inhibitor. Ref: H. Matsuda, et al, Tetrahedron, 1996, 52, 14501 HO

HO H O

HO O

N H

O S

OH

O

H

OH

H H N

N

N

3

H

O

NH NH2

O

131 Aeruginosin 102B Type: Aeruginosins. C33H44N6O11S Amorph. powder. Source: Cyanobacterium Microcystis viridis NEIS 102. Pharm: Thrombin inhibitor. Ref: H. Matsuda, et al, Tetrahedron, 1996, 52, 14501 HO HO H O HO O

N H

O S

OH

O

H

NH

N

3

H

O

OH

H H N

N

NH2

O

132 Aeruginosin 103A Type: Aeruginosins. C35H48N6O8 Amorph. powder, [α]D = −7.6° (c = 0.1, MeOH). Source: Cyanobacterium Microcystis viridis NEIS 102. Pharm: Thrombin inhibitor. Ref: S. Kodani, et al, JNP, 1998, 61, 1046 HO HO H O HO O

O S

O

OH

H N H

O

OH

H H N

N H

3

O

N

NH NH2

1.3 Aeruginosins

47

133 Aeruginosin 205A Type: Aeruginosins. C34H53ClN6O12S Microcryst., [α]D20 = 17.7° (c = 0.1, MeOH). Source: Cyanobacterium Oscillatoria agardhii NIES 205 (fresh water). Pharm: Serine protease inhibitor. Ref: H. J. Shin, et al, JOC, 1997, 62, 1810│N. Valls, et al, Tet. Lett., 2006, 47, 3701│K. Ersmark, et al, Angew. Chem., Int. Ed., 2008, 47, 1202 H N H OH O HO

S

NH2

H N

O

HN Cl

O

O

OH

N

O

H

3

O

O

2

N H

O 2'

HO

134 Aeruginosin 205B Type: Aeruginosins. C34H53ClN6O12S [α]D20 = 40.3° (c = 0.1, MeOH). Source: Cyanobacterium Oscillatoria agardhii NIES 205 (fresh water). Pharm: Serine protease inhibitor. Ref: H. J. Shin, et al, JOC, 1997, 62, 1810│N. Valls, et al, Tet. Lett., 2006, 47, 3701│K. Ersmark, et al, Angew. Chem., Int. Ed., 2008, 47, 1202 H N H OH O HO

S O

O

NH2

H N

O

HN Cl

O OH

N

O

H

3

O

2

N H

O 2'

HO

135 Aeruginosin 298A Type: Aeruginosins. C30H48N6O7 Amorph. powder, [α]D = 22.3° (c = 0.36, H2O). Source: Cyanobacterium Microcystis aeruginosa NIES-298 (fresh water). Pharm: Thrombin inhibitor; trypsin inhibitor. Ref: M. Murakami, et al, Tet. Lett., 1994, 35, 3129│K. Ishida, et al, Tetrahedron, 1999, 55, 10971│K. Ersmark, et al, Angew. Chem., Int. Ed., 2008, 47, 1202 (rev)

48

1 Peptides

HO H HO

H O N H

1

N

12

O

NH

H N

NH2

N H

O

OH

OH

136 Aeruginosin 89B Type: Aeruginosins. C30H45ClN6O10S [α]D23 = 9.4° (c = 0.1, MeOH). Source: Cyanobacterium Microcystis aeruginosa. Pharm: Serine protease inhibitor. Ref: K. Ishida, et al, Tetrahedron, 1999, 55, 10971│K. Ersmark, et al, Angew. Chem., Int. Ed., 2008, 47, 1202 HO

H H

OH

H N

N

2

O O

N H

N

1

NH NH2

O

OH Cl O HO S O O

137 Aeruginosin 98A Type: Aeruginosins. C29H45ClN6O9S Amorph. powder, [α]D = −7.6° (c = 0.2, H2O). Source: Cyanobacterium Microcystis aeruginosa NIES98. Pharm: Thrombin inhibitor; trypsin inhibitor; serine proteases inhibitor. Ref: M. Murakami, et al, Tet. Lett., 1995, 36, 278│K. Ishida, et al, Tetrahedron, 1999, 55, 10971│K. Ersmark, et al, Angew. Chem., Int. Ed., 2008, 47, 1202 H

N

O O

S OH

O

O

H O

H N

N H O

H N

NH NH2

H HO Cl OH

1.3 Aeruginosins

49

138 Aeruginosin 98B Type: Aeruginosins. C29H46N6O9S Amorph. powder, [α] = −5.2° (c = 0.2, H2O). Source: Cyanobacterium Microcystis aeruginosa NIES98. Pharm: Thrombin inhibitor; trypsin inhibitor; serine proteases inhibitor; plasmin inhibitor. Ref: M. Murakami, et al, Tet. Lett., 1995, 36, 278│K. Ishida, et al, Tetrahedron, 1999, 55, 10971│ K. Ersmark, et al, Angew. Chem., Int. Ed., 2008, 47, 1202 H

N

O S

O

OH

O

H O

O

H N

H N

N H O

NH NH2

H HO

OH

139 Aeruginosin 98C Type: Aeruginosins. C29H45BrN6O9S Powder, [α] = −13° (c = 0.25, H2O). Source: Cyanobacterium Microcystis aeruginosa NIES98. Pharm: Serine protease inhibitor. Ref: M. Murakami, et al, Tet. Lett., 1995, 36, 278│K. Ishida, et al, Tetrahedron, 1999, 55, 10971│K. Ersmark, et al, Angew. Chem., Int. Ed., 2008, 47, 1202 H

O O

S

O OH

O N

H O

H N

H N

N H O

NH NH2

H HO Br

3'

OH

140 Aeruginosin KY608 Type: Aeruginosins. C29H45ClN6O6 Powder, [α]D25 = −5° (c = 0.3, MeOH). Source: Cyanobacterium Microcystis sp. IL-323. Pharm: Trypsin inhibitor. Ref: A. Raveh, et al, Phytochem. Lett., 2009, 2, 10 H

HO

O N

H O

H N

N H O

H N

NH NH2

H HO Cl OH

50

1 Peptides

141 Aeruginosin KY642 Type: Aeruginosins. C29H44Cl2N6O6 Yellow powder, [α]D25 = −1° (c = 0.06, MeOH). Source: Cyanobacterium Microcystis sp. IL-323. Pharm: Trypsin inhibitor. Ref: A. Raveh, et al, Phytochem. Lett., 2009, 2, 10 H

O N

HO

H O

H N

N H O

H N

NH NH2

H HO Cl OH

Cl

142 Chlorodysinosin A Type: Aeruginosins. C26H43ClN6O10S Amorph. solid. Source: Sponge Dysidea sp. Pharm: Thrombin inhibitor; factor VIIa inhibitor; factor Xa inhibitor. Ref: Pat. Coop. Treaty (WIPO), 2003, 03 51 831; CA, 139, 47155 H

HO

H N

14 +

Cl

N

O

N

HO

H

O

NH2

O H

O

N H

NH2

O

S O

O –

O

143 Dysinosin A Type: Aeruginosins. C26H44N6O10S Amorph. solid. Source: An unidentified sponge (family Dysideidae, Australia). Pharm: Inhibitor of factor VIIa (Ki = 0.108 μmol/L); inhibitor of thrombin (Ki = 0.452 μmol/L). Ref: A. R. Carroll, et al, JACS, 2002, 124, 13340

HO

N 14

HO

H

N

N

O O

NH2 NH2

O N H

+

O

S O

O –

O

1.3 Aeruginosins

51

144 Dysinosin B Type: Aeruginosins. C31H52N6O15S Amorph. solid, [α]D25 = +72° (c = 0.02, MeOH). Source: Sponge Lamellodysidea chlorea (Australia). Pharm: Inhibitor of factor VIIa (Ki = 0.090 μmol/L); inhibitor of thrombin (Ki = 0.170 μmol/L). Ref: A. R. Carroll, et al, JNP, 2004, 67, 1291 OH HO

O

HO

O HO

H

H N

14

N

N

O

H

O

NH2 NH2

O

HO

+

O

N H O

S O

O –

O

145 Dysinosin C Type: Aeruginosins. C25H42N6O10S Amorph. solid. Source: Sponge Lamellodysidea chlorea (Australia). Pharm: Inhibitor of factor VIIa (Ki = 0.124 μmol/L); inhibitor of thrombin (Ki = 0.550 μmol/L). Ref: A. R. Carroll, et al, JNP, 2004, 67, 1291 H

HO

H N

14

N

HO

N

O

H

+

O

NH2

O O

N H

NH2

S O

O O

146 Dysinosin D Type: Aeruginosins. C25H42N6O7 Amorph. solid. Source: Sponge Lamellodysidea chlorea (Australia). Pharm: Inhibitor of factor VIIa (Ki = 1.32 μmol/L); inhibitor of thrombin (Ki > 5.1 μmol/L). Ref: A. R. Carroll, et al, JNP, 2004, 67, 1291 H

HO

H N

14

HO

N

N

O

H

O –

O O

NH2 NH2

O N H

+

52

1 Peptides

147 Microcin SF608 Type: Aeruginosins. C32H44N6O6 [α]D25 = −19.1° (c = 1, MeOH). Source: Cyanobacterium Microcystis sp. Pharm: Trypsin inhibitor. Ref: R. Banker, et al, Tetrahedron, 1999, 55, 10835 HN NH2 N H H

H N N

HO

H O

OH

OH

O H N O

148 Oscillarin Type: Aeruginosins. C34H44N6O5 Source: Cyanobacterium Oscillatoria agardhii B2 83 Pharm: Thrombin inhibitor; trypsin inhibitor; anti-inflammatory; cerebroprotective. Ref: S. Hanessian, et al, JACS, 2004, 126, 6064 H

NH2

O

NH

N H

N

HO

N

H O OH HN O

1.4 Tripeptides 149 Antibiotic K 26 Type: Tripeptides. C25H34N3O8P mp 300 °C (browning), [α]D20 = −4.8° (c = 0.1, H2O). Source: An unidentified actinomycete K-26. Pharm: Hypotensive. Ref: M. Yamato, et al, J. Antibiot., 1986, 39, 44

O N H

H N O

H N O

P O

OH OH

1.4 Tripeptides

53

150 Belamide A Type: Tripeptides. C35H48N4O5 Yellow oil, [α]D25 = +16° (c = 0.002, CHCl3). Source: Cyanobacterium Symploca sp. (Panama). Pharm: Anticancer-Cell-Effect (model: rat aorta A-10 cells, mechanism: microtubule disruption at 20 μmol/L; antimitotic); cytotoxic (HCT116, IC50 = 0.74 μmol/L). Ref: T. L. Simmons, et al, Tetrahedron Lett. 2006, 47, 3387│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev)

O O N

N

N

N

O

O

O

151 Carmaphycin A Type: Tripeptides. C25H45N3O6S Source: Cyanobacterium Symploca sp. (CARMABI, Curaçao). Pharm: Peptidic proteasome inhibitor; inhibits β5 subunit (chymotrypsinlike activity) (Symploca cerevisiae 20Sproteasome, strong); cytotoxic (lung and coloncancer cells, strong); antiproliferative (HTCLs). Ref: A. R. Pereira, et al, Chem Bio Chem, 2012, 13, 810 S O

O O

H N

O

N H

O

H N O

152 Carmaphycin B Type: Tripeptides. C25H45N3O7S Source: Cyanobacterium Symploca sp. (CARMABI, Curaçao). Pharm: Peptidic proteasome inhibitor; inhibits β5 subunit (chymotrypsinlike activity) (Symploca cerevisiae 20S proteasome, strong); cytotoxic (lung and colon cancer cells, strong); antiproliferative (HTCLs). Ref: A. R. Pereira, et al, Chem Bio Chem, 2012, 13, 810

O O O

S

O O

H N O

N H

H N O

54

1 Peptides

153 Dibenarthin Type: Tripeptides. C34H48N10O13 Source: Marine-derived streptomycete Streptomyces sp. from brown alga Analipus japonicus (Charatsunai beach, Muroran, Japan). Pharm: Siderophore; iron chelating activity (comparable to that of deferoxamine mesylate). Ref: Y. Matsuo, et al, JNP, 2011, 74, 2371 OH HO

O NH H 2N

O

HN N H

O

O O

O

H N

N H

OH O

NH

OH

NH

HO

HN

NH2

HO

154 Fellutamide A Type: Tripeptides. C27H49N5O8 Amorph. powder, [α]D22 = −12.7° (c = 1, MeOH). Source: Marine-derived fungus Penicillium fellutanum from an unidentified fish. Pharm: Cytotoxic (P388, IC50 = 0.2 μg/mL; several cell lines); NGF inducer. Ref: H. Shigemori, et al, Tetrahedron, 1991, 47, 8529│K. Yamaguchi, et al, Biosci., Biotechnol., Biochem., 1993, 57, 195 NH2 OH

O H N

O N H

O

O N H H OH

O

O H

NH2

155 Fellutamide B Antibiotic 1656B Type: Tripeptides. C27H49N5O7 Amorph. powder, mp 185–186 °C, [α]D21 = −24.7° (c = 0.5, MeOH). Source: Marine-derived fungus Penicillium fellutanum from an unidentified fish. Pharm: Cytotoxic (P388, IC50 = 0.1 μg/mL; several cell lines); NGF inducer. Ref: H. Shigemori, et al, Tetrahedron, 1991, 47, 8529│K. Yamaguchi, et al, Biosci., Biotechnol., Biochem., 1993, 57, 195 NH2 OH

O H N

O N H

O N H H

O

1''

O

NH2

O H

1.4 Tripeptides

55

156 Fellutamide C Type: Tripeptides. C27H51N5O7 Source: Marine-derived fungus Aspergillus versicolor from sponge Petrosia sp. (Jeju I., R. O. Korea). Pharm: Cytotoxic (A549, ED50 = 18.42 μg/mL, control Doxorubicin, ED50 = 0.01 μg/mL; SK-OV-3, ED50 = 13.28 μg/mL, Doxorubicin, ED50 = 0.06 μg/mL; SK-MEL-2, ED50 = 2.83 μg/mL, Doxorubicin, ED50 = 0.04 μg/mL; XF498, ED50 = 2.16 μg/mL, Doxorubicin, ED50 = 0.12 μg/mL; HCT15, ED50 = 1.74 μg/mL, Doxorubicin, ED50 = 0.18 μg/mL). Ref: Y. M. Lee, et al, Bull. Korean Chem. Soc., 2010, 31, 205│Y. M. Lee, et al, Bull. Korean Chem. Soc., 2011, 32, 3817 O OH

NH2 O H N

O N H

8

O

OH N H

NH2

157 Fellutamide F Type: Tripeptides. C28H53N5O8 Light violet amorphous powder, [α]D = +163° (c = 0.13, MeOH). Source: Marine-derived fungus Aspergillus versicolor fromsponge Petrosia sp. (Jeju I., R. O. Korea). Pharm: Cytotoxic (A549, ED50 = 1.81 μg/mL, control Doxorubicin, ED50 = 0.01 μg/mL; SK-OV-3, ED50 = 1.20 μg/mL, Doxorubicin, ED50 = 0.06 μg/mL; SK-MEL-2, ED50 = 0.67 μg/mL, Doxorubicin, ED50 = 0.04 μg/mL; XF498, ED50 = 0.14 μg/mL, Doxorubicin, ED50 = 0.12 μg/mL; HCT15, ED50 = 0.13 μg/mL, Doxorubicin, ED50 = 0.18 μg/mL). Ref: Y. M. Lee, et al, Bull. Korean Chem. Soc., 2011, 32, 3817 H 2N O OH 8

O N H

H N

HO O N H

O

O

OH

NH2

158 Hemiasterlin Milnamide B Type: Tripeptides. C30H46N4O4 Cryst. (MeOH/hexane),mp 120–130 °C, [α]D = −95° (c = 0.06, MeOH). Source: Sponge Hemiasterella minor. Pharm: Cytotoxic (A498, IC50 = 0.0224 μg/mL; OVCAR-3, IC50 = 1 × 10-6 μg/mL; SF539, IC50 = 0.0013 μg/mL; Colon205, IC50 = 0.0001 μg/mL; NCI-H460, IC50 = 1 × 10-6 μg/mL; LOX, IC50 = 1.5984 μg/mL; MDA-MB-435, IC50 = 0.0154 μg/mL) (Gamble, 1999);

56

1 Peptides

cytotoxic (microtubule formation inhibitor). Ref: P. Talpir, et al, Tet. Lett., 1994, 35, 4453│R. J. Andersen, et al, Tet. Lett., 1997, 38, 317│W. R. Gamble, et al, Bioorg. Med. Chem., 1999, 7, 1611

O

O

NH

N

N

N H

OH

O

159 Hemiasterlin A Type: Tripeptides. C29H44N4O4 Amorph. solid, [α]D = −45° (c = 0.25, MeOH). Source: Sponge Cymbastela sp. (Papua New Guinea). Pharm: Cytotoxic (in vitro and in vivo, U373, ED50 = 0.015 μg/mL, HEY, ED50 = 0.0076 μg/mL) (Coleman, 1995); cytotoxic (A498, IC50 = 0.3158 μg/mL; OVCAR-3, IC50 = 0.0024 μg/mL; SF539, IC50 = 0.0061 μg/mL; Colon205, IC50 = 0.0009 μg/mL; NCI-H460, IC50 = 0.0001 μg/mL) (Gamble, 1999). Ref: J. E. Coleman, et al, Tetrahedron, 1995, 51, 10653│ W. R. Gamble, et al, Bioorg. Med. Chem., 1999, 7, 1611

O

N H

O N

N H

HN

OH

O

160 Hemiasterlin B Type: Tripeptides. C28H42N4O4 Amorph. solid. Source: Sponge Cymbastela sp. (Papua New Guinea). Pharm: Cytotoxic (in vitro and in vivo, P388, ED50 = 0.007 μg/mL, MCF7, ED50 = 0.066 μg/mL, HEY, ED50 = 0.016 μg/mL). Ref: J. E. Coleman, et al, Tetrahedron, 1995, 51, 10653 O

N H

HN

O N H

N

OH

O

161 Hemiasterlin C Type: Tripeptides. C29H44N4O4 [α]D = −18.8° (c = 0.11, MeOH). Source: Sponges Auletta sp. and Siphonochalina sp. (two collections). Pharm: Cytotoxic (A498, IC50 = 0.5321 μg/mL; OVCAR-3, IC50 = 0.0066 μg/mL; SF539, IC50 = 0.0775 μg/mL; Colon205, IC50 = 0.0087 μg/mL; NCI-H460, IC50 = 0.0015 μg/mL; LOX, IC50 = 1.1135 μg/mL; MDA-MB-435, IC50 = 0.4002 μg/mL). Ref: W. R. Gamble, et al, Bioorg. Med. Chem., 1999, 7, 1611

1.4 Tripeptides

O

HN

N

57

O N

N H

OH

O

162 Janolusimide Type: Tripeptides. C19H33N3O5 [α]D25 = −10.3° (c = 2.5, CHCl3). Source: Nudibranch Janolus cristatus. Pharm: Neurotoxin; atropine antagonist; LD50 (mus, ipr) = 5 mg/kg. Ref: G. Sodano, et al, Tet. Lett., 1986, 27, 2505│A. Giordano, et al, Tet. Lett., 2000, 41, 3979 O O OH

N O

H N O

N H

163 (+)-Jasplakinolide Z1 Type: Tripeptides. C36H47BrN4O7 White solid, [α]D23 = +48° (c = 0.05, MeOH). Source: Sponge Jaspis splendens. Pharm: Cytotoxic (HCT116, GI50 = 13.7 μmol/L; MDA-MB-231, GI50 = 2.50 μmol/L); cytotoxic (selected NCI 60 cell line screening results, IGROV1, GI50 = 1.76 μmol/L; U251, GI50 = 0.60 μmol/L; NCI-H522, GI50 = 0.12 μmol/L; DU145, GI50 = 18.8 μmol/L; LOX-IMVI, GI50 = 0.28 μmol/L). Ref: K. R. Watts, et al, JNP, 2011, 74, 341 OH

H N Br

O

H N

HO OH

N O

O O

NH

164 (+)-Jasplakinolide Z2 Type: Tripeptides. C37H49BrN4O7 White solid, [α]D23 = +46° (c = 0.05, MeOH). Source: Sponge Jaspis splendens. Pharm: Cytotoxic (HCT116, GI50 = 0.27 μmol/L). Ref: K. R. Watts, et al, JNP, 2011, 74, 341

58

1 Peptides

OH

H N Br

O

H N

O

N O

OH

O O

NH

165 (+)-Jasplakinolide Z3 Jaspamide Z3 Type: Tripeptides. C38H51BrN4O7 White solid, [α]D23 = +64° (c = 0.05, MeOH). Source: Sponge Jaspis splendens (Korovou Bay, Fiji). Pharm: Cytotoxic (HCT116, GI50 = 0.28 μmol/L; MDA-MB-231, GI50 = 0.74 μmol/L); cytotoxic (selected NCI 60 cell line screening results, IGROV1, GI50 = 0.17 μmol/L; U251, GI50 = 0.05 μmol/L; NCI-H522, GI50 = 0.04 μmol/L; DU145, GI50 = 3.72 μmol/L; A498, GI50 = 0.44 μmol/L; LOX-IMVI, GI50 = 0.16 μmol/L). Ref: A. M. J. Senderowicz, et al, J. Natl. Cancer Inst., 1995, 87, 46│K. R. Watts, et al, JNP, 2011, 74, 341 H N Br HO H N O

N O

O

O O

NH

HO

166 (–)-Jasplakinolide Z4 Jaspamide Z4 Type: Tripeptides. C27H39BrN4O4 White solid, [α]D22 = −32° (c = 0.05, MeOH). Source: Sponge Jaspis splendens (Korovou Bay, Fiji). Pharm: Cytotoxic (HCT116, GI50 = 11.1 μmol/L; MDA-MB-231, GI50 = 22.3 μmol/L). Ref: A. M. J. Senderowicz, et al, J. Natl. Cancer Inst., 1995, 87, 46│K. R. Watts, et al, JNP, 2011, 74, 341 H N Br HO H N O O HO

N O

O O

NH

1.4 Tripeptides

59

167 Spiroidesin Type: Tripeptides. C35H43N3O7 Amorph. solid, [α]D25 = −62° (c = 0.56, MeOH). Source: Cyanobacterium Anabaena spiroides. Pharm: Cell growth inhibitor (Microcystis aeruginosa). Ref: K. Kaya, et al, JNP, 2002, 65, 920 OH

O N H

O

H N

O

N H

O

OH

OH

168 Terpeptin A Type: Tripeptides. C28H40N4O4 Pale yellow powder, [α]D25 = +43.9° (c = 0.1, MeOH). Source: Mangrove-derived fungus Aspergillus sp. W-6 from mangrove Acanthus ilicifolius (China waters). Pharm: Cytotoxic (A549, IC50 = 23.3 μmol/L). Ref: Z. Lin, et al, Magn. Reson. Chem., 2008, 46, 1212 O N H 3

O N O

N H

O

N H

169 Terpeptin B Type: Tripeptides. C28H40N4O4 Pale yellow powder, [α]D25 = −104.6° (c = 0.1, MeOH). Source: Mangrove-derived fungus Aspergillus sp. W-6 from mangrove Acanthus ilicifolius (China waters). Pharm: Cytotoxic (A549, IC50 = 28.0 μmol/L). Ref: Z. Lin, et al, Magn. Reson. Chem., 2008, 46, 1212 O N H 3

N H

O

O N O

N H

60

1 Peptides

170 Tokaramide A Type: Tripeptides. C23H36N6O5 Pale yellow solid, [α]D29 = −19° (c = 0.06, MeOH). Source: Lithistid sponge Theonella aff. mirabilis (Japan waters). Pharm: Antineoplastic (Cathepsin B inhibitor). Ref: N. Fusetani, et al, Bioorg. Med Chem. Lett., 1999, 9, 3397 HO

O

H N

N H

O

O

H N O

H2N

H

NH N H

1.5 Linear Oligopeptides (4–10 residues) 171 Acyclodidemnin A Type: Linear oligopeptides. C49H80N6O13 mp 126–130 °C, [α]D26 = −71° (c = 0.06, CHCl3). Source: Ascidian Trididemnum solidum (Caribbean Sea). Pharm: Cytotoxic (P388, IC50 = 0.2 μg/mL). Ref: R. Sakai, et al, JACS, 1995, 117, 8885 O

N

N

COOH

O O O

HO

NH O

O

O

OH

O

NH NH

O HN

172 Almiramide A Type: Linear oligopeptides. C39H64N6O7 Colorless glass, [α]D22 = −169.1° (c = 0.2, MeOH). Source: Cyanobacterium Lyngbya majuscula (Bocas del Toro, Panama). Pharm: Antileishmanial (in vitro, Leishmania donovani, IC50 > 13.5 μmol/L). Ref: L. M. Sanchez, et al, JMC, 2010, 53, 4187

1.5 Linear Oligopeptides (4–10 residues)

O N

H N

N

O

O

61

O N

N

O

NH2

O

O

173 Almiramide B Type: Linear oligopeptides. C39H62N6O6 Colorless glass, [α]D22 = −148.9° (c = 0.1, MeOH). Source: Cyanobacterium Lyngbya majuscula (Bocas del Toro, Panama). Pharm: Antileishmanial (in vitro, Leishmania donovani, IC50 = 2.4 μmol/L); cytotoxic (Vero cells, IC50 = 52.3 μmol/L, SI = 21.8). Ref: L. M. Sanchez, et al, JMC, 2010, 53, 4187 O N

H N

N

O

O

O N

N

O

NH2

O

174 Almiramide C Type: Linear oligopeptides. C40H66N6O6 Colorless glass, [α]D22 = −136.8° (c = 0.1, MeOH). Source: Cyanobacterium Lyngbya majuscula (Bocas del Toro, Panama). Pharm: Antileishmanial (in vitro, Leishmania donovani, IC50 = 1.9 μmol/L); cytotoxic (Vero, IC50 = 33.1 μmol/L, SI = 17.4). Ref: L. M. Sanchez, et al, JMC, 2010, 53, 4187 O N O

H N

N O

O

O N

N

NH2

O

175 Alterobactin B Type: Linear oligopeptides. C36H55N11O19 Source: Marine bacterium Alteromonas luteoviolacea. Pharm: Siderophore (exceptional affinity for ferric ion, Ka = 1049–1053). Ref: R. T. Reid, et al, Nature, 1993, 366, 455

62

1 Peptides

OH O O

OH H O

HO O

H N NH O

H N

OH

N H

H N

H 2N OH

N H

N H

H N

H O HO

OH O

OH O O

N H

O HO

NH2

176 Amphibactin B Type: Linear oligopeptides. C38H69N7O14 Source: Marine bacterium Vibrio sp. R-10. Pharm: Amphiphilic siderophore. Ref: J. S. Martinez, et al, Proc. Natl. Acad. Sci. USA, 2003, 100, 3754 O

O N

H N OH

O

H N

N H

O

N

O

N

OH

OH

O N H OH

OH O

OH

O

177 Amphibactin S Type: Linear oligopeptides. C38H67N7O13 Source: Marine-derived bacterium Vibrio sp. (Santa Barbara basin, Southern California, USA). Pharm: Siderophore. Ref: J. M. Vraspir, et al, Bio Metals, 2011, 24, 85

1.5 Linear Oligopeptides (4–10 residues)

O

N

OH

N H

O

O

O

O

H N

N H

5

OH

N O

O

H N

OH

63

O

OH

N OH

178 Amphibactin T Type: Linear oligopeptides. C36H65N7O13 Source: Marine-derived bacterium Vibrio sp. (Santa Barbara basin, Southern California, USA). Pharm: Siderophore. Ref: J. M. Vraspir, et al, Bio Metals, 2011, 24, 85

H N

N H

O

OH N O

O

H N

OH N

O

O

O N H

O

OH

OH O

N OH

179 Aquachelin I Type: Linear oligopeptides. C44H76N10O21 Source: Marine-derived bacterium Halomonas meridiana (Santa Barbara basin, Southern California, USA). Pharm: Siderophore. Ref: J. M. Vraspir, et al, Bio Metals, 2011, 24, 85 OH

HN

O

O

OH NH

HO HN

COOH

O

OH

N H

O

O

OH

N

N O

O

H N

OH

NH2

H N O

O

O N H OH

COOH

64

1 Peptides

180 Aquachelin J Type: Linear oligopeptides. C42H72N10O20 Source: Marine-derived bacterium Halomonas meridiana (Santa Barbara basin, Southern California, USA). Pharm: Siderophore. Ref: J. M. Vraspir, et al, Bio Metals, 2011, 24, 85

HN

O

O

OH NH

HO HN

COOH

O

OH

N

H N

N H

O

OH

N O

O

H N

OH

O

O COOH

N H

O

OH

NH2

O

181 Bisebromoamide Type: Linear oligopeptides. C51H72BrN7O8S Oil, [α]D22 = +17.8° (c = 1,CHCl3). Source: Cyanobacterium Lyngbya sp. (Okinawa). Pharm: Protein kinase inhibitors (selectively inhibits phosphorylation of ERK (extracellular signal regulated protein kinase) in NRK cells by PDGF (platelet-derived growth factor)-stimulation, 10–0.1 μmol/L; no effect on phosphorylation of AKT, PKD, PLCγ1, or S6 ribosomal protein, 10–0.1 μmol/L); cytotoxic (HeLa-S3 cells, IC50 = 40 ng/mL); cytotoxic (panel of 39 hmn cancer cell lines (termed JFCR39), mean GI50 = 40 nmol/L); anticancer-Cell-Effect (model: normal rat kidney cells extracellular signal regulated protein kinase, mechanism: protein kinase inhibition) (Teruya, 2009); anticancer-Cell-Effect (model: hmn HeLa epithelial carcinoma cells, mechanism: actin filaments stabilization) (Sumiya, 2011). Ref: T. Teruya, et al, Org. Lett., 2009, 11, 5062│X. Gao, et al, Org. Lett., 2010, 12, 3018 (structure revised)│H. Sasaki, et al, Tetrahedron, 2011, 67, 990 (structure revised)│E. Sumiya, et al, ACS Chem. Biol. 2011, 6, 425

O

O N N N

HN O O

S O Br OH

N H

N O

O N

1.5 Linear Oligopeptides (4–10 residues)

65

182 Callipeltin C Type: Linear oligopeptides. C68H118N18O21 [α]D = −15.3° (c = 0.0053, MeOH). Source: Lithistid sponge Callipelta sp. (New Caledonia). Pharm: Antifungal (Candida albicans, 100 μg/disc, IZD = 9 mm). Ref: A. Zampella, et al, JACS, 1996, 118, 6202│ M. V. D’Auria, et al, Tetrahedron, 1996, 52, 9589│A. Zampella, et al, Tet. Lett., 2002, 43, 6163 O 2'

NH NH2

HN

NH2

OH HN

H H N H O

2'' 3''

H N H

HO

O

HN

OH HO

NH

O

O

OH

O

NH H2N

O

NH

NH

O OO

HN HOOC

O

N O

OH

N

N H H

O NH2

183 Callipeltin F Type: Linear oligopeptides. C42H79N13O14 Amorph. solid, [α]D25 = −4.3° (c = 0.35, MeOH). Source: Sponge Latrunculia sp. Pharm: Antifungal (standard disk assay, inhibits growth of Candida albicans ATCC 24433, MIC = 1 × 10–4 mol/L). Ref: V. Sepe, et al, Tetrahedron, 2006, 62, 833 O

NH2

H H N

HN

N H H 3''

OH

O

NH H 2N

OH

N H

O OH

O O

H N

HO

H H N

2''

O O

OH

O

NH OH

N H

NH2

N H

184 Callipeltin G Type: Linear oligopeptides. C54H100N16O17 Amorph. solid, [α]D25 = −5.3° (c = 0.26, MeOH). Source: Sponge Latrunculia sp. Pharm: Antifungal (standard disk assay,

66

1 Peptides

inhibits growth of Candida albicans ATCC 24433, MIC = 1 × 10–4 mol/L). Ref: V. Sepe, et al, Tetrahedron, 2006, 62, 833 NH2

O

H H N

HN

N H H 3''

O HO

H 2N

OH

O

N

OH

O NH

N H

N H

O

NH

N H

O

OH

H N

O

O

H H N

2''

O OH

OH

O

O

NH2

NH2

N H

185 Callipeltin H Type: Linear oligopeptides. C68H116N18O20 Amorph. solid, [α]D25 = −4.5° (c = 0.71, MeOH). Source: Sponge Latrunculia sp. Pharm: Antifungal (standard disk assay, inhibits growth of Candida albicans ATCC 24433, MIC = 1 × 10–4 mol/L). Ref: V. Sepe, et al, Tetrahedron, 2006, 62, 833

2'

NH2

HN

NH

NH2

NH

O

OH

NH

O

OH

H2N OH

O

H N N H H O

2'' 3''

N H H HN

HO

O

HN

NH

O

NH

O OO

O HOOC

N

OH O

N H H

N

O NH2

186 Callipeltin I Type: Linear oligopeptides. C42H77N13O13 Amorph. solid, [α]D25 = +1.3° (c = 0.37, MeOH). Source: Sponge Latrunculia sp. Pharm: Antifungal (standard disk assay, inhibits growth of Candida albicans ATCC 24433, MIC = 1 × 10–4 mol/L). Ref: V. Sepe, et al, Tetrahedron, 2006, 62, 833

1.5 Linear Oligopeptides (4–10 residues)

O

NH2

HN

N H O

O

NH

OH

O

NH

3''

H N

HO

O

H H N

2''

O OH

O

OH

O

H H N

H 2N

67

OH

N H

N H

NH2

N H

187 Callipeltin J Type: Linear oligopeptides. C31H58N8O11 Amorph. solid, [α]D25 = −1.2° (c = 0.09, MeOH). Source: Sponge Latrunculia sp. Pharm: Antifungal (Candida albicans, MIC = 1 μmol/L). Ref: M. V. D’Auria, et al, Tetrahedron, 2007, 63, 131 O OH

NH H 2N

N H

O

NH

O

OH

N H

NH2

H H N O

O OH OH

HN O OH

188 Callipeltin K Type: Linear oligopeptides. C67H116N18O21 Amorph. solid, [α]D25 = −7° (c = 1.12, MeOH). Source: Sponge Latrunculia sp. Pharm: Antifungal (Candida albicans, MIC = 1 μmol/L). Ref: M. V. D’Auria, et al, Tetrahedron, 2007, 63, 131

68

1 Peptides

O

NH NH2 OH

HN

O

NH

NH

NH2 2'

O

O

H H N N H H O HO HO

OH

NH

O

N H H HN

2'' 3''

O O OO

HN O HOOC

H2N OH

N

OH O

NH

N

N H H

O

189 Carmabin A Type: Linear oligopeptides. C40H57N5O6 Amorph. solid, [α]D27 = −109° (c = 0.4, MeOH); white amorphous solid, [α]D25 = −137° (c = 0.440, CHCl3). Source: Cyanobacteria Lyngbya majuscula (Panama) and Tolypothrix sp. (Curacao). Pharm: Antiproliferative; Antiplasmodial (Plasmodium falciparum W2, IC50 = 4.3 μmol/L). Ref: G. J. Hooper, et al, JNP, 1998, 61,529

O

9

O N

O H N

O

N

O

N

O

NH2

190 Citronamide A Type: Linear oligopeptides. C39H59N7O15 Gum, [α]D = −15° (c = 0.04, MeOH). Source: Sponge Citronia astra (Day Reef, Queensland, Australia). Pharm: Antifungal (Saccharomyces cerevisiae, baker’s yeast, MIC = 8 μg/mL). Ref: A. R. Carroll, et al, JNP, 2009, 72, 764 O COOH O O

OH

O

O OH

N H

NH2

H N

H N

NH2

O

NH

O H N O

H

O OH O

1.5 Linear Oligopeptides (4–10 residues)

69

191 Citronamide B Type: Linear oligopeptides. C39H59N7O15 Gum, [α]D = −17° (c = 0.03, MeOH). Source: Sponge Citronia astra (Day Reef, Queensland, Australia). Pharm: Antifungal (Saccharomyces cerevisiae, baker’s yeast, moderate). Ref: A. R. Carroll, et al, JNP, 2009, 72, 764 O

O

COOH O

O O

OH

H 2N

NH2

H N

H N

OH

N H

O

O NH

O

H N H

O OH O

192 Criamide A Type: Linear oligopeptides. C35H56N8O5 Amorph. solid, [α]D = +97° (c = 0.02, MeOH). Source: Sponge Cymbastela sp. (Papua New Guinea). Pharm: Cytotoxic (in vitro and in vivo). Ref: J. E. Coleman, et al, Tetrahedron, 1995, 51, 10653

O

O

1

N H

N H

NH

N

O

HO

N H

O

NH

HN

NH2

193 Criamide B Type: Linear oligopeptides. C36H58N8O5 Amorph. solid. Source: Sponge Cymbastela sp. (Papua New Guinea). Pharm: Cytotoxic (in vitro and in vivo: P388, ED50 = 0.0073 μg/mL, MCF7, ED50 = 6.8 μg/mL, U373, ED50 = 0.27 μg/mL, HEY, ED50 = 0.19 μg/mL, LoVo, ED50 = 0.15 μg/mL, A549, ED50 = 0.29 μg/mL). Ref: J. E. Coleman, et al, Tetrahedron, 1995, 51, 10653

1

N

NH

O

HO O

O N H

N

N H

O HN

NH NH2

70

1 Peptides

194 Deoxymajusculamide D Type: Linear oligopeptides. C43H65N5O9 Source: Cyanobacterium Lyngbya majuscula. Pharm: Cytotoxic (CCRF-CEM cell culture system, 0.2 μg/mL). Ref: R. E. Moore, et al, Phytochemistry, 1988, 27, 3101 O O

H N

N O

O

4'

N

N O

O

N

O O

O

195 Desacetylmicrocolin B Type: Linear oligopeptides. C37H63N5O7 Source: Cyanobacterium Lyngbya cf. polychroa (Hollywood, Florida). Pharm: Cytotoxic (HT29 and IMR-32, cell growth inhibitor). Ref: T. Meickle, et al, PM, 2009, 75, 1427 O N O

H N

N O

O N

N OH

O

O

196 Dolastatin 10 Type: Linear oligopeptides. C42H68N6O6S Amorph. powder (MeOH/CH2Cl2), mp 107–112 °C, [α]D29 = −68° (c = 0.01, MeOH). Source: Cyanobacterium Symploca sp. VP642, sea hare Dolabella auricularia, an unidentified shell-less mollusc. Pharm: Antineoplastic (hmn melanoma, dose 3.25–26 μg/kg, effective rate = 17%–67%; B16 melanoma, dose 1.44–11.1 μg/kg, effective biotic prolonged rate = 42%–138%, PS, dose 1–4 μg/kg, effective biotic prolonged rate = 69%–102%, ED50 = 4.6 × 10-5 μg/mL) (Pettit, 1987); cytotoxic ([3H] Thymidine assay, several hmn lymphoma cell lines) (Beckwith, 1993); cytotoxic (MTT assay, hmn DU145) (Turner, 1998); cytotoxic and antineoplastic (MTT assay, hmn lung cancer cells: NCI-H69, NCI-H82, NCI-H446 and NCI-H510) (Kalemkerian, 1999); antineoplastic (Phase II Clinical Trial, 2000, lacked clinically significant activity); cytotoxic (trypan blue dye assay, reh lymphoblastic leukemia) (Wall, 1999); anticancer-Cell-Effect (model: hmn reh lymphoblastic leukemia cells, mechanism: Bcl-2 protein reduction) (Wall, 1999); anticancer-Cell-Effect (model: hmn lung cancer cells: NCI-H69 and NCI-H510, mechanism: Bcl-2 protein phosphorylation) (Kalemkerian, 1999); antineoplastic (Phase II Clinical Trial, 2000, Lacked clinically significant activity) (Hoffman, 2003); anticancer-Cell-Effect (model: hmn A549, mechanism: bad protein levels

1.5 Linear Oligopeptides (4–10 residues)

71

increase) (Catassi, 2006); anticancer-Cell-Effect (model: hmn A549, mechanism: caspase-3 protein activation) (Catassi, 2006); antimitotic; fungicidal; tubulin polymerisation inhibitor. Ref: G. R. Pettit, et al, JACS, 1987, 109, 6883; 1989, 111, 5463│M. Beckwith, et al, J. Natl. Cancer Inst. 1993, 85, 483│G. R. Pettit, et al, Tetrahedron, 1993, 49, 9151│F. Roux, et al, Tetrahedron, 1994, 50, 5345│R. K. Pettit, et al, Antimicrob. Agents Chemother., 1998, 42, 2961│G. P. Kalemkerian, et al, Cancer Chemother. Pharm. 1999, 43, 507│N. R. Wall, et al, Leuk. Res. 1999, 23, 881│G. P. Kalemkerian, et al, Cancer Chemother. Pharm. 1999, 43, 507│H. Luesch, et al, JNP, 2001, 64, 907│M. A. Hoffman, et al, Gynecol. Oncol., 2003, 89, 95│B. J. Fennell,et al, J. Antimicrob. Chemother. 2003, 51, 833│A. Catassi, et al, Cell. Mol. Life Sci., 2006, 63, 2377│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev)

O

H N

O

NH

O

O

N H

O O

N

HN

N

S

197 Dolastatin 15 Type: Linear oligopeptides. C45H68N6O9 Powder, mp 143–148 °C, [α]D26 = −26° (c = 0.01, MeOH). Source: An unidentified cyanobacterium, sea hare Dolabella auricularia (Indian Ocean). Pharm: Cytotoxic (inhibits growth of P388, ED50 = 0.0024 μg/mL); antimalarial (IC50 = 200 nmol/L); microtubule inhibitor. Ref: G. R. Pettit, et al, JOC, 1989, 54, 6005│G. R. Pettit, et al, Tetrahedron, 1993, 49, 9151│G. R. Pettit, et al, Tetrahedron, 1994, 50, 12 097│K. Akaji, et al, JOC, 1999, 64, 405│B. J. Fennell,et al, J. Antimicrob. Chemother. 2003, 51, 833

O H N

N O

O N

N O

N

O O

O

N

H

O

O

198 Dragomabin Type: Linear oligopeptides. C37H51N5O6 Amorph. solid, [α]D25 = −106° (c = 0.5, CHCl3). Source: Cyanobacterium Lyngbya majuscula (Panama). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 6.0 μmol/L). Ref: K. L. McPhail, et al, JNP, 2007, 70, 984

72

1 Peptides

O O N

O N

N H

O

NH2

N

O

O

199 Dragonamide A Dragonamide Type: Linear oligopeptides. C37H59N5O5 Amorph. solid, [α]D20 = −260.8° (c = 2.6, CH2Cl2); pale yellow oil, [α]D25 = −244° (c = 0.250, CHCl3). Source: Cyanobacterium Lyngbya majuscula (Panama). Pharm: Cytotoxic (A549, HT29 and MEL28); antiplasmodial (Plasmodium falciparum W2, IC50 = 7.7 μmol/L). Ref: J. I. Jimenez, et al, JNP 2001, 64, 200│H. Chen, et al, Tetrahedron, 2005, 61, 11132│K. L. McPhail, et al, JNP, 2007, 70, 984

O

O 3'

N

2'

N

N

NH2

N O

O

O

200 Dragonamide E Type: Linear oligopeptides. C37H57N5O5 Amorph. solid, [α]D25 = −220° (c = 1.66, MeOH). Source: Cyanobacterium Lyngbya majuscula. Pharm: Antileishmanial (Leishmania donovani, IC50 = 5.1 μmol/L). Ref: M. J. Balunas, et al, JNP, 2010, 73, 60

O

O N

3' 2'

O

N

N O

NH2

N O

201 Gymnangiamide Type: Linear oligopeptides. C36H59N7O10 Amorph. solid, [α]D = −32.5° (c = 0.24, MeOH). Source: Hydroid Gymnangium regae. Pharm: Cytotoxic (Colon205, IC50 = 4.7 μg/mL, H460, IC50 = 0.46 μg/mL, K562, IC50 = 11.5 μg/mL, Molt4, 5.8 μg/mL, A549, IC50 = 5.8 μg/mL, MALME-3M, IC50 = 9.6 μg/mL; LOX, OVCAR-3 and SNB19, inhibition but no IC50 data; MCF7, 15 μg/mL, inactive; IC-2WT, IC50 = 1.7 μg/mL). Ref: D. J. Milanowski, et al, JOC, 2004, 69, 3036│H. Tone, et al, Org. Lett., 2009, 11, 1995 (structure revised)

1.5 Linear Oligopeptides (4–10 residues)

H N

H 2N

NH

O N H OH

H H N O

O

O

H

OH

HO O

N

H

N H

73

H COOH

202 Halovir A Type: Linear oligopeptides. C45H83N7O9 Amorph. solid, [α]D = −13° (c = 0.73, MeOH). Source: Marine-derived fungus Scytalidium sp. Pharm: Antiviral (in vitro HSV-1 and HSV-2 inhibitor, direct inactivation, potent). Ref: D. C. Rowley, et al, Bioorg. Med. Chem., 2003, 11, 4263│M. Saleem, et al, NPR, 2007, 24, 1142 (rev)│ S. Z. Moghadamtousi, et al, Mar. Drugs, 2015, 13, 4520 (rev) OH O

4'

N H

H H N

N

O N H

O

O

O

H N

N H

O O

OH

NH2

203 Halovir B Type: Linear oligopeptides. C43H79N7O9 Amorph. solid, [α]D = −8° (c = 0.25, MeOH). Source: Marine-derived fungus Scytalidium sp. Pharm: Antiviral (in vitro HSV-1 and HSV-2 inhibitor, direct inactivation, potent). Ref: D. C. Rowley, et al, Bioorg. Med. Chem., 2003, 11, 4263│S. Z. Moghadamtousi, et al, Mar. Drugs, 2015, 13, 4520 (rev) OH O

4'

N H

N O

H H N O

O N H

O

H N

N H

O O

OH

NH2

204 Halovir C Type: Linear oligopeptides. C45H83N7O8 Amorph. solid, [α]D = −20° (c = 0.38, MeOH). Source: Marine-derived fungus Scytalidium sp. Pharm: Antiviral (in vitro HSV-1 and HSV-2 inhibitor, direct inactivation, potent). Ref: D. C. Rowley, et al, Bioorg. Med. Chem., 2003, 11, 4263│S. Z. Moghadamtousi, et al, Mar. Drugs, 2015, 13, 4520 (rev)

74

1 Peptides

O

O

4'

N H

H H N

N

N H

O

O

O

H N

N H

O

OH O

NH2

205 Halovir D Type: Linear oligopeptides. C43H79N7O9 Amorph. solid, [α]D = −27° (c = 0.28, MeOH). Source: Marine-derived fungus Scytalidium sp. Pharm: Antiviral (in vitro HSV-1 and HSV-2 inhibitor, direct inactivation, potent). Ref: D. C. Rowley, et al, Bioorg. Med. Chem., 2003, 11, 4263│S. Z. Moghadamtousi, et al, Mar. Drugs, 2015, 13, 4520 (rev) OH O

4'

N H

N

H H N

O N H

O

O

O

H N

N H

O O

OH

NH2

206 Halovir E Type: Linear oligopeptides. C43H79N7O8 Amorph. solid, [α]D = −14° (c = 0.42, MeOH). Source: Marine-derived fungus Scytalidium sp. Pharm: Antiviral (in vitro HSV-1 and HSV-2 inhibitor, direct inactivation, potent). Ref: D. C. Rowley, et al, Bioorg. Med. Chem., 2003, 11, 4263│S. Z. Moghadamtousi, et al, Mar. Drugs, 2015, 13, 4520 (rev)

O

4'

N H

N O

H H N O

O N H

O

H N

N H

O O

OH

NH2

207 Koshikamide A1 Type: Linear oligopeptides. C66H100N12O15 Amorph. solid, [α]D25 = −156° (c = 0.19, MeOH). Source: Lithistid sponge Theonella sp. (Japan waters). Pharm: Cytotoxic (P388, IC50 = 2.2 μg/mL); cytotoxic (P388, IC50 = 1.7 μmol/L). Ref: N. Fusetani, et al, Tet. Lett., 1999, 40, 4687│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

1.5 Linear Oligopeptides (4–10 residues)

75

O NH2 O H N

O N

O

N H

O

O

H

OH N

N

O O

O

H

N

NH2 O N

O N

N

O

O

O

N H

208 Loihichelin A Type: Linear oligopeptides. C44H73N11O19 Source: Marine bacterium Halomonas sp. LOB-5 (Loihi seamount, Hawaii). Pharm: Amphiphilic siderophore. Ref: V. V. Homann, et al, JNP, 2009, 72, 884 OH N O HN O O

HO HN H 2N

N H

O

O O

HO O

O

N OH

OH O

H N

N H

O

OH H N

O

H N

N H

O OH

209 Loihichelin B Type: Linear oligopeptides. C46H77N11O20 Source: Marine bacterium Halomonas sp. LOB-5 (Loihi seamount, Hawaii). Pharm: Amphiphilic siderophore. Ref: V. V. Homann, et al, JNP, 2009, 72, 884 OH N O H N

HN HO

O HN

H 2N O

O N H

OH

O N H

O

H N O O

HO O

H N O OH

O

OH O N H

N OH OH

76

1 Peptides

210 Loihichelin C Type: Linear oligopeptides. C46H75N11O19 Source: Marine bacterium Halomonas sp. LOB-5 (Loihi seamount, Hawaii). Pharm: Amphiphilic siderophore. Ref: V. V. Homann, et al, JNP, 2009, 72, 884 OH N O H N

HN HO

O O

HN H 2N

N H

O

H N O O

HO O

OH

O

N OH

OH O

H N

N H

O

OH

O

N H

O

211 Loihichelin D Type: Linear oligopeptides. C46H77N11O19 Source: Marine bacterium Halomonas sp. LOB-5 (Loihi seamount, Hawaii). Pharm: Amphiphilic siderophore. Ref: V. V. Homann, et al, JNP, 2009, 72, 884 OH N O H N

HN HO

O HN

H 2N O

O

N H

OH

O N H

O

H N O O

HO O

H N O OH

OH O

O

N OH

N H

212 Loihichelin E Type: Linear oligopeptides. C48H79N11O19 Source: Marine bacterium Halomonas sp. LOB-5 (Loihi seamount, Hawaii). Pharm: Amphiphilic siderophore. Ref: V. V. Homann, et al, JNP, 2009, 72, 884

1.5 Linear Oligopeptides (4–10 residues)

77

OH N O H N

HN HO

O O

HN H 2N

N H

O

H N O O

HO O

O

N OH

OH O

H N

N H

O

OH

O

N H

O OH

213 Loihichelin F Type: Linear oligopeptides. C48H81N11O19 Source: Marine bacterium Halomonas sp. LOB-5 (Loihi seamount, Hawaii). Pharm: Amphiphilic siderophore. Ref: V. V. Homann, et al, JNP, 2009, 72, 884 OH N O H N

HN HO

O O

HN H 2N

N H

O

H N O O

HO O

O

N OH

OH O

H N

N H

O

OH

O

N H

O OH

214 Majusculamide D Type: Linear oligopeptides. C43H65N5O10 Source: Cyanobacterium Lyngbya majuscula. Pharm: Cytotoxic (CCRF-CEM cell culture system, 0.2 μg/mL). Ref: R. E. Moore, et al, Phytochemistry, 1988, 27, 3101 O OH O

H N

N O

O

O

O

4'

N

N O

N

O O

78

1 Peptides

215 Malevamide D Type: Linear oligopeptides. C40H68N4O8 Oil, [α]D26 = −55° (c = 0.1, MeOH). Source: Cyanobacterium Symploca hydnoides. Pharm: Cytotoxic (P388, A549, HT29 and MEL28, subnanomolar range). Ref: F. D. Horgen, et al, JNP, 2002, 65, 487

O

H H N

N

O

N

N

O

O

H

O

O HO

O

216 N-Methylated octapeptide RHM3 Type: Linear oligopeptides. C51H93N9O11 [α]D27 = −52.6° (c = 0.23, MeOH). Source: Marine-derived fungus Acremonium sp. Pharm: Reinvestigation of same fungal strain revealed presence of additional RHM congeners, RHM3 and RHM4. Ref: C. M. Boot, et al, Tetrahedron, 2007, 63, 9903 OH O N NH2

O O N H

O

H N O

N O

H N

N O

O

O

N

N O

217 Microcolin A Type: Linear oligopeptides. C39H65N5O9 Glass, [α]D25 = −145.3° (c = 0.003, EtOH). Source: Cyanobacteria Lyngbya majuscula and Lyngbya cf. polychroa. Pharm: MLR Inhibitor (hmn two-way mixed lymphocyte response (MLR), EC50 = 0.02 nmol/L); immunosuppressive (mus, inhibits mixid-lymphocyte response and P388). Ref: F. E. Koehn, et al, JNP, 1992, 55, 613│F. E. Koehn, et al, JMC, 1994, 37, 3181│C. P. Decicco, et al, JOC, 1996, 61, 3534│K. Sharp, et al, Appl. Environ. Microbiol., 2009, 75, 2879│T. Meickle, et al, PM, 2009, 75, 1427

1.5 Linear Oligopeptides (4–10 residues)

79

O N O

O

H N

N O

O

N

N

OH

O

O O

218 Microcolin B Type: Linear oligopeptides. C39H65N5O8 Glass, [α]D25 = −174° (c = 0.005, EtOH). Source: Cyanobacterium Lyngbya majuscula (Venezuela). Pharm: Immunosuppressive (mus, inhibits mixid-lymphocyte response and P388). Ref: F. E. Koehn, et al, JNP, 1992, 55, 613│F. E. Koehn, et al, JMC, 1994, 37, 3181│K. Sharp, et al, Appl. Environ. Microbiol., 2009, 75, 2879│T. Meickle, et al, PM, 2009, 75, 1427

O

O N

N O

N

N O

O

N

O O

219 Miraziridine A Type: Linear oligopeptides. C30H52N8O9 [α]D20 = −74° (c = 0.085, MeOH). Source: Lithistid sponge Theonella aff. mirabilis (off Amami and Tokara Islands, Japan). Pharm: Antiosteoporosis (Cathepsin B model, IC50 = 2.1 μmol/L); cysteine protease inhibitor; amino-protease inhibitor; serine protease inhibitor. Ref: P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

O

O HO N

N H

H N O

OH

O N H

O

H N

OH

O

NH

H N H

NH2

220 Nazumamide A Type: Linear oligopeptides. C28H43N7O8 Amorph. powder, [α]D23 = +87.1° (c = 0.075, MeOH). Source: Lithistid sponge Theonella sp. Pharm: Thrombin inhibitor. Ref: N. Fusetani, et al, Tet. Lett., 1991, 32, 7073│V. L. Nienaber, JACS, 1996, 118, 6807

80

1 Peptides

H N

H 2N NH

HO

O N H

O

H N

N O

O

OH

N H

O

OH

221 Nobilamide B Type: Linear oligopeptides. C43H64N6O19 Source: Marine-derived streptomycete Streptomyces sp. (Chicoreus nobilis, Cebu, Philippines) from an unidentified mollusc. Pharm: Long-acting antagonists of mouse and hmn transient receptor potential vanilloid-1 (TRPV1) channels (potent, pain and in ammation mediators). Ref: M. Gorlero, et al, FEBS Lett., 2009, 583, 153│Z. Lin, et al, JMC, 2011, 54, 3746

O HO

HO

O

H N O

O

H N

N H

N H

O

O

H N

O NH

NH O

222 Norbisebromoamide Type: Linear oligopeptides. C50H70BrN7O8S Oil, [α]D22 = +11.5° (c = 0.82, CHCl3). Source: Cyanobacterium Lyngbya sp. Pharm: Cytotoxic (HeLa-S3, IC50 = 45 ng/mL). Ref: H. Sasaki, et al, Tetrahedron, 2011, 67, 990

N

H

N N

HN O

O

S

O

O N H

N

O N

O

O Br OH

223 Plicatamide Type: Linear oligopeptides. C59H68N14O9 Source: Ascidian Styela plicata (San Diego Bay). Pharm: Antimicrobial. Ref: J. A. Tincu, et al, Biochem. Biophys. Res. Commun., 2000, 270, 421

1.5 Linear Oligopeptides (4–10 residues)

HN H N

H2N

O N H

O

HN

N

N

O

H N

81

H N

N H

O

O

O

NH

O HO

NH NH N

HO

224 Pseudotheonamide A1 Type: Linear oligopeptides. C36H45N9O8 Amorph. solid, [α]D29 = −28° (c = 0.085, MeOH). Source: Lithistid sponge Theonella swinhoei (Japan waters). Pharm: Serine protease inhibitor; thrombin inhibitor (IC50 = 1.0 μmol/L); trypsin inhibitor (IC50 = 4.5 μmol/L). Ref: Y. Nakao, et al, ACS, 1999, 121, 2425│R. Samy, et al, JOC, 1999, 64, 2711│T. Hu, et al, JOC, 1999, 64, 3000│S. M. Bauer, et al, JACS, 1999, 121, 6355 OH

H O

HN O Ph

NH HN O H

HO

N

N H

O

O

N

N H

NH NH

O

225 Pseudotheonamide A2 Type: Linear oligopeptides. C36H45N9O8 Amorph. solid, [α]D29 = −34° (c = 0.065, MeOH). Source: Lithistid sponge Theonella swinhoei (Japan waters). Pharm: Serine protease inhibitor; thrombin inhibitor (IC50 = 31.0 μmol/L); trypsin inhibitor (IC50 > 10 μmol/L). Ref: Y. Nakao, et al, ACS, 1999, 121, 2425│R. Samy, et al, JOC, 1999, 64, 2711│T. Hu, et al, JOC, 1999, 64, 3000│S. M. Bauer, et al, JACS, 1999, 121, 6355 OH

H O

HN O Ph

NH HN O H

N H

HO

N O

O

N H

N

NH NH

82

1 Peptides

226 Pseudotheonamide B2 Type: Linear oligopeptides. C37H45N9O8 Amorph. solid, [α]D29 = −17° (c = 0.050, MeOH). Source: Lithistid sponge Theonella swinhoei (Japan waters). Pharm: Serine protease inhibitor; thrombin inhibitor (IC50 = 1.3 μmol/L); trypsin inhibitor (IC50 = 6.2 μmol/L). Ref: Y. Nakao, et al, ACS, 1999, 121, 2425│R. Samy, et al, JOC, 1999, 64, 2711│T. Hu, et al, JOC, 1999, 64, 3000│S. M. Bauer, et al, JACS, 1999, 121, 6355 OH

H

O

HN N

N

O

O Ph

H

HO N

N

N H

O

O

N H

NH NH

O

227 Pseudotheonamide C Type: Linear oligopeptides. C36H45N9O8 Amorph. solid, [α]D29 = −16° (c = 0.047, MeOH). Source: Lithistid sponge Theonella swinhoei (Japan waters). Pharm: Serine protease inhibitor; thrombin inhibitor (IC50 = 0.19 μmol/L); trypsin inhibitor (IC50 = 3.8 μmol/L). Ref: Y. Nakao, et al, ACS, 1999, 121, 2425│R. Samy, et al, JOC, 1999, 64, 2711│T. Hu, et al, JOC, 1999, 64, 3000│S. M. Bauer, et al, JACS, 1999, 121, 6355 OH

O

HN NH2

O Ph

H O

N

N H

HO N

N O

O

N H

NH NH

228 Pseudotheonamide D Type: Linear oligopeptides. C29H36N6O6 Amorph. solid, [α]D29 = −11° (c = 0.085, MeOH). Source: Lithistid sponge Theonella swinhoei (Japan waters). Pharm: Serine protease inhibitor; thrombin inhibitor (IC50 = 1.4 μmol/L); trypsin inhibitor (IC50 > 10 μmol/L). Ref: Y. Nakao, et al, ACS, 1999, 121, 2425│R. Samy, et al, JOC, 1999, 64, 2711│T. Hu, et al, JOC, 1999, 64, 3000│S. M. Bauer, et al, JACS, 1999, 121, 6355

1.5 Linear Oligopeptides (4–10 residues)

83

OH

O

HN NH2

O Ph

H O

N

N H

N NH2

O

O

229 Symplocin A Type: Linear oligopeptides. C56H86N8O13 Source: Cyanobacterium Symploca sp. (San Salvador Is., Bahamas). Pharm: Protease enzyme cathepsin E inhibitor (potent). Ref: T. F. Molinski, et al, JNP, 2012, 75, 425 HO O OH

O

NH

HN

HN O

O

NH

HN O N

O

O N

O

O

O

N

O

230 Symplostatin 1 Type: Linear oligopeptides. C43H70N6O6S [α]D = −45° (c = 1.6, MeOH). Source: Cyanobacteria Phormidium spp. (assemblage), Cyanobacterium Symploca hydnoides. Pharm: Anticancer-Cell-Effect (model: rat aorta A-10 and hmn HeLa cells, mechanism: cell cycle inhibition); anticancer-Cell-Effect (model: rat aorta A-10 cells, mechanism: microtubule depolymerization); anticancer-Cell-Effect (model: MDA-MB-435, mechanism: Bcl-2 protein phosphorylation); anticancer-Cell-Effect (model: MDA-MB-435, mechanism: caspase-3 protein activity stimulation); antineoplastic (PS, ED50 = 0.046 ng/mL, NCI hmn melanoma xenograph, mus in vivo); cytotoxic (SRB assay, MDA-MB-435 and NCI-ADR); cytotoxic (KB, IC50 = 0.3 ng/mL, LoVo cell lines); tubulin polymerisation inhibitor; toxic (iv, low doses, causing lethality on day 1). Ref: G. R. Pettit, et al, JACS, 1987, 109, 6883│G. G. Harrigan, et al, JNP, 1998, 61, 1075│H. Luesch, et al, JNP, 2001, 64, 907│S. L. Mooberry, et al, Int. J. Cancer 2003, 104, 512│L. A. Salavador, et al, JNP, 2010, 73, 1606│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev)

84

1 Peptides

O

H

N

N O

O

O

NH

O H

O

N

HN

N

S

231 Symplostatin 3 Type: Linear oligopeptides. C40H66N4O9 Amorph. solid, [α]D24 = −46° (c = 0.35, MeOH). Source: Cyanobacterium Symploca sp. VP452. Pharm: Anticancer-Cell-Effect (model: rat aorta A-10 cells, mechanism: microtubule depolymerization); cytotoxic (hmn tumor cell lines, IC50 = 3.9–10.3 μmol/L). Ref: H. Luesch, et al, JNP, 2002, 65, 16│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev)

H N

N

O

H

H

O

O

O

O

N

N

COOH

O

O

232 Tasiamide A Type: Linear oligopeptides. C42H67N7O10 Amorph. powder, [α]D21 = +15° (c = 0.4, CHCl3). Source: Cyanobacterium Symploca sp. Pharm: Cytotoxic (KB, IC50 = 0.48 μg/ mL; LoVo, IC50 = 3.47 μg/mL). Ref: P. G. Williams, et al, JNP, 2002, 65, 1336

O N

N O

O

H

H N O

O

O N

N H

O

N H

OH

O O

NH2

233 Tasiamide B Type: Linear oligopeptides. C50H74N8O12 Amorph. powder, [α]D21 = −28° (c = 0.4, MeOH). Source: Cyanobacterium Symploca sp. Pharm: Cytotoxic (KB, IC50 = 0.8 μmol/L). Ref: P. G. Williams, et al, JNP, 2003, 66, 1006

1.5 Linear Oligopeptides (4–10 residues)

O N O

O

O

H N

N O

85

N H

O

OH NH

O N

O

O O

NH2

NH OH

234 Tauramamide Type: Linear oligopeptides. C44H65N9O9 Pale yellow glass (Me ester), [α]D25 = −14.6° (c = 0.6, MeOH) (Me ester). Source: Marine-derived bacterium Brevibacillus laterosporus. Pharm: Antibacterial (Enterococcus sp., MIC = 0.1 μg/mL). Ref: K. Desjardine, et al, JNP, 2007, 70, 1850 H N

OH O

H N

N H

O

O N H OH

NH

O

H N

OH

N H

O

NH2

O

N H

235 Thiochondrilline C Type: Linear oligopeptides. C25H31N5O7S3 White solid, [α]D25 = −77° (c = 0.0011, CHCl3). Source: Marine-derived bacterium Verrucosispora sp. from lithistid sponge Chondrilla caribensis f. caribensis (Florida Keys, USA). Pharm: Cytotoxic (A549, EC50 = 2.86 μmol/L). Ref: T. P. Wyche, et al, JOC, 2011, 76, 6542 S OH H N N

O O

H N

O S N

N O

O O

S

86

1 Peptides

236 Trichoderin A Type: Linear oligopeptides. C60H110N10O12 Amorph. solid, [α]D20 = −17° (c = 0.7, MeOH). Source: Marine-derived fungus Trichoderma sp. 05F148 from an unidentified sponge. Pharm: Antimycobacterial (Mycobacterium smegmatis, Mycobacterium bovis and Mycobacterium tuberculosis, MIC = 0.02–2.0 μg/mL, against both actively growing and dormant states). Ref: P. Pruksakorn, et al, Bioorg. Med. Chem. Lett., 2010, 20, 3658

H N

N

O N H

O O

H N O

O

H H N

N H

O

OH 6'' 7''

O O

N H

NH

O

O

HO

NH

N

237 Trichoderin A1 Type: Linear oligopeptides. C60H108N10O11 Amorph. solid, [α]D20 = −23° (c = 0.3, MeOH). Source: Marine-derived fungus Trichoderma sp. 05F148 from an unidentified sponge. Pharm: Antimycobacterial (Mycobacterium smegmatis, Mycobacterium bovis and Mycobacterium tuberculosis, MIC = 0.02–2.0 μg/mL, against both actively growing and dormant states). Ref: P. Pruksakorn, et al, Bioorg. Med. Chem. Lett., 2010, 20, 3658

H N

N O

O N H

H N O

O N H

H H N O

O N H

O NH

O 6'' 7''

O O

HO

NH

N

238 Trichoderin B Type: Linear oligopeptides. C59H108N10O12 Amorph. solid, [α]D20 = −59° (c = 0.1, MeOH). Source: Marine-derived fungus Trichoderma sp. 05F148 from an unidentified sponge. Pharm: Antimycobacterial (Mycobacterium smegmatis, Mycobacterium bovis and Mycobacterium tuberculosis, MIC = 0.02–2.0 μg/mL, against both actively growing and dormant states). Ref: P. Pruksakorn, et al, Bioorg. Med. Chem. Lett., 2010, 20, 3658

1.6 Linear Polypeptides

O

H N

N

H N

N H

O O

O

O

O

H H N

N H

N H

O

OH 6'' 7''

O

O

87

O NH NH

N

HO

1.6 Linear Polypeptides 239 Aspereline A Type: Linear polypeptides. C45H80N10O11 Needles (MeOH), mp 296–298 °C, [α]D20 = −42° (c = 0.1, MeOH). Source: Marine-derived fungus Trichoderma asperellum Y19-07 (psychrophilic, from sediment sample, Antarctic). Pharm: Antifungal (phytopathogenic fungi Alternaria solani and Pyricularia oryzae, weak); antibacterial (Staphylococcus aureus and Escherichia coli). Ref: J. W. Ren, et al, JNP, 2009, 72, 1036

H N O

O N H

H N O

O N H

O

H N

N H

O

Ac-1Aib-Aib-Val-Aib-5Ile-Aib-Aib-Ala-Aib-10Pro-ol

HN

O NH O

O NH

N

O

OH

240 Aspereline B Type: Linear polypeptides. C44H78N10O11 Needles (MeOH), mp 273–275 °C, [α]D20 = −5° (c = 0.1, MeOH). Source: Marine-derived fungus Trichoderma asperellum Y19-07 (psychrophilic, from sediment sample, Antarctic). Pharm: Antifungal (phytopathogenic fungi Alternaria solani and Pyricularia oryzae, weak); antibacterial (Staphylococcus aureus and Escherichia coli). Ref: J. W. Ren, et al, JNP, 2009, 72, 1036

88

1 Peptides

H N

O

H

O

N H

H N

O N H

O

O

H N

N H

O

HN

O NH O

O NH O

N

OH

241 Aspereline C Type: Linear polypeptides. C44H78N10O11 Needles (MeOH), mp 284–285 °C, [α]D20 = −22° (c = 0.1, MeOH). Source: Marine-derived fungus Trichoderma asperellum Y19-07 (psychrophilic, from sediment sample, Antarctic). Pharm: Antifungal (phytopathogenic fungi Alternaria solani and Pyricularia oryzae, weak); antibacterial (Staphylococcus aureus and Escherichia coli). Ref: J. W. Ren, et al, JNP, 2009, 72, 1036

H N O

O N H

H N O

O N H

O

H N

N H

O

H HN

O NH O

O NH N

O OH

242 Aspereline D Type: Linear polypeptides. C44H78N10O11 Needles (MeOH), mp 301–303 °C, [α]D20 = −10.5° (c = 0.1, MeOH). Source: Marine-derived fungus Trichoderma asperellum Y19-07 (psychrophilic, from sediment sample, Antarctic). Pharm: Antifungal (phytopathogenic fungi Alternaria solani and Pyricularia oryzae, weak); antibacterial (Staphylococcus aureus and Escherichia coli). Ref: J. W. Ren, et al, JNP, 2009, 72, 1036

1.6 Linear Polypeptides

H N

O N H

O

H N

O N H

O

89

O

H N

N H

O

HN

O NH O

O NH N

O OH

243 Aspereline E Type: Linear polypeptides. C45H80N10O12 Needles (MeOH), mp 295–297 °C, [α]D20 = −12° (c = 0.1, MeOH). Source: Marine-derived fungus Trichoderma asperellum Y19-07 (psychrophilic, from sediment sample, Antarctic). Pharm: Antifungal (phytopathogenic fungi Alternaria solani and Pyricularia oryzae, weak); antibacterial (Staphylococcus aureus, Escherichia coliand Pseudomonas aeruginosa); cytotoxic (HL60, weak). Ref: J. W. Ren, et al, JNP, 2009, 72, 1036

H N O

O N H

H N O

O N H

O

H N

N H

O

HN

O NH O

O NH

N

OH

O OH

244 Aspereline F Type: Linear polypeptides. C46H82N10O11 Needles (MeOH), mp 281–283 °C, [α]D20 = −12° (c = 0.1, MeOH). Source: Marine-derived fungus Trichoderma asperellum Y19-07 (psychrophilic, from sediment sample, Antarctic). Pharm: Antifungal (phytopathogenic fungi Alternaria solani and Pyricularia oryzae, weak); antibacterial (Staphylococcus aureus and Escherichia coli). Ref: J. W. Ren, et al, JNP, 2009, 72, 1036

90

1 Peptides

O

H N

H N H

O

O

H N

N H

O

O

H N

O

N H

O

NH O

HN O NH O

N

OH

245 Bogorol A Type: Linear polypeptides. C80H142N16O16 Amorph. solid, [α]D25 = −38.2° (MeOH). Source: Marine-derived bacterium Brevibacillus laterosporus PNG-276. Pharm: Antibacterial (MRSA and VREF). Ref: T. Barsby, et al, Org. Lett., 2001, 3, 437│ T. Barsby, et al, JOC, 2006, 71, 6031 OH OH O

HN

NH O NH2

O

HN

NH O HN

O NH

OH

O

H N

O N H

H N O

O N H

H H N O NH2

O N H

H N

O

O H2N

246 Dictyonamide A Type: Linear polypeptides. C63H108N12O15 Amorph. solid, [α]D22 = −169° (c = 1, MeOH). Source: An unidentified marine-derived fungus K063 from red alga Ceratodictyon spongiosum (Okinawa). Pharm: Kinases inhibitor (CDK4, IC50 = 16.5 μg/mL, cyclin-dependent). Ref: K. Komatsu, et al, JOC, 2001, 66, 6189│ M. Saleem, et al, NPR, 2007, 24, 1142 (rev)

1.6 Linear Polypeptides

OH

O H 2N

HO

H N H

O

N 3''

O HO

O

H

N

N

O N

N H

O

O

O

N

O

O

H N

O

H N

N

H

91

N O

247 Efrapeptin Eα Type: Linear polypeptides. C82H142N18O16 Amorph. solid, [α]D27 = +5° (c = 0.23, MeOH), [α]D28 = −2° (c = 0.2, CHCl3). Source: Marine-derived fungus Acremonium sp. Pharm: Cytotoxic (H125, IC50 = 1.3 nmol/L). Ref: C. M. Boot, et al, Tetrahedron, 2007, 63, 9903 O

O N

N

N

O

N H

O

H N O

N H

O

N

N H

O

N H

O O

H N

O

H N

N H

O O

HN HN

H N

N O

O

H N

HN

O

O

248 Efrapeptin F Type: Linear polypeptides. C82H141N18O161+ [α]D22 = −5° (c = 0.4, CHCl3). Source: Marine-derived fungus Acremonium sp. Pharm: luciferase inhibitor (inhibits 2-deoxyglucose-induced luciferase expression, reporter gene assay, dose-dependent, with 2-deoxyglucose 10 mmol/L for 18 hours to treat HT1080 cells to increase luciferase activity about 5-fold compared with control, inhibitor IC50 = 8.5 nmol/L); cytotoxic (H125, IC50 = 1.3 nmol/L). Ref: C. M. Boot, et al, Tetrahedron, 2007, 63, 9903│Y. Hayakawa, et al, J. Antibiot., 2008, 61, 365

92

1 Peptides

O

O N

N

N

O

H N

N H

O

O

HN HN

H N

N H

O

O

N H

O

H N

N H

O

O

N

O

H N

+

O

N H

N O

HN

H N

O

O

O

249 Efrapeptin G Type: Linear polypeptides. C83H143N18O161+ [α]D22 = −5.3° (c = 0.42, CHCl3). Source: Marine-derived fungus Acremonium sp. Pharm: luciferase inhibitor (inhibits 2-deoxyglucose-induced luciferase expression, reporter gene assay, dose-dependent, with 2-deoxyglucose 10 mmol/L for 18 hours to treat HT1080 cells to increase luciferase activity about 5-fold compared with control, inhibitor IC50 = 3.3 nmol/L); cytotoxic (H125, IC50 = 1.3 nmol/L). Ref: C.M.Boot, et al,JNP, 2006, 69, 83│C. M. Boot, et al, Tetrahedron, 2007, 63, 9903│Y. Hayakawa, et al, J. Antibiot., 2008, 61, 365 O

O N

N

N

+

O

N H

O

H N O

N H

O

N

N H

O

N H

O O

H N

O

H N

N H

O O

HN HN

H N

N O

O

H N

HN

O

O

250 Efrapeptin J Type: Linear polypeptides. C81H139N18O161+ Powder, mp 132–137 °C, [α]D23 = +14° (c = 0.24, MeOH). Source: Marine-derived fungus Tolypocladium sp. AMB18 (sea mud, Japan waters). Pharm: luciferase inhibitor (inhibits 2-deoxyglucose-induced luciferase expression, reporter gene assay, dose-dependent, with 2-deoxyglucose 10 mmol/L for 18 hours to treat HT1080 cells to increase luciferase activity about 5-fold compared with control, inhibitor IC50 = 18 nmol/L); inhibits protein expression of molecular chaperone GRP78 (HT1080 and MKN74); cell death inducer (HT1080, under endoplasmic reticulum stress). Ref: Y. Hayakawa, et al, J. Antibiot., 2008, 61, 365

1.6 Linear Polypeptides

O

93

O N

O

N H

O

N

O

H N

N H

O

N H

O

O

HN HN

N

N

O

H N

+

H N

N H

O

O N H

O

H N

N O

H N

O

HN

O

O

251 Grassystatin A Type: Linear polypeptides. C58H95N9O16 Source: Cyanobacterium Lyngbya confervoides (Grassy Key and Key Largo, Florida). Pharm: Anticancer-Cell-Effect (model: cathepsins D and E, mechanism: proteases inhibition); aspartic proteases inhibitor (protease cathepsin D, IC50 = 26.5 nmol/L, control pepstatin A, IC50 = 173 pmol/L; protease cathepsin E, IC50 = 886 pmol/L, control pepstatin A, IC50 = 181 pmol/L; protease ADAM9, IC50 = 46.1 μmol/L*, control GM6001, IC50 = 56.3 nmol/L; protease ADAM10, IC50 > 100 μmol/L*, control GM6001, IC50 = 263 nmol/L; protease TACE, IC50 = 1.23 μmol/L*, control GM6001, IC50 = 13.1 nmol/L, *calculated from later part of progress curves). Ref: J. C. Kwan, et al, JMC, 2009, 52, 5732

N O

O

N O

O O O O

OH NH

O HN O

O

NH2 O HO

N H

N

O O

H N O

N H

252 Grassystatin B Type: Linear polypeptides. C59H97N9O16 Source: Cyanobacterium Lyngbya confervoides (Grassy Key and Key Largo, Florida). Pharm: Anticancer-Cell-Effect (model: cathepsins D and E, mechanism: proteases inhibition); aspartic proteases inhibitor (protease cathepsin D, IC50 = 7.27 nmol/L, control pepstatin A, IC50 = 173 pmol/L; protease cathepsin E, IC50 = 354 pmol/L, control pepstatin A, IC50 = 181 pmol/L; protease ADAM9, IC50 = 85.5 μmol/L*, control GM6001, IC50 = 56.3 nmol/L; protease ADAM10, IC50 = 87.2 μmol/L*, control GM6001, IC50 = 263 nmol/L; protease TACE,

94

1 Peptides

IC50 = 2.23 μmol/L*, control GM6001, IC50 = 13.1 nmol/L, *calculated from later part of progress curves). Ref: J. C. Kwan, et al, JMC, 2009, 52, 5732

N N O

O

O

O

O

H N

OH

H N

O

O

O

N H

NH2 O

N

O

O O

NH

O

HO O

N H

253 Grassystatin C Type: Linear polypeptides. C50H82N8O12 Source: Cyanobacterium Lyngbya confervoides (Grassy Key and Key Largo, Florida). Pharm: Aspartic proteases inhibitor (protease cathepsin D, IC50 = 1.62 μmol/L, control Pepstatin A, IC50 = 173 pmol/L; protease cathepsin E, IC50 = 42.9 nmol/L, Pepstatin A, IC50 = 181 pmol/L; protease ADAM9, IC50 > 100 μmol/L*, control GM6001, IC50 = 56.3 nmol/L; protease ADAM10, IC50 > 100 μmol/L*, GM6001, IC50 = 263 nmol/L; protease TACE, IC50 = 28.6 μmol/L*, GM6001, IC50 = 13.1 nmol/L, *calculated from later part of progress curves). Ref: J. C. Kwan, et al, JMC, 2009, 52, 5732

NH2 O

50

48

HO

45

H N

33

O

39

HO

37

O N

19

O H N O

28

25

N H

H N O

O O

O

17

O

N 7

N 1

5

6

254 Halicylindramide E Type: Linear polypeptides. C68H96BrN17O17S Powder (as Na salt), [α]D = +9° (c = 0.3, MeOH) (Na salt). Source: Sponge Halichondria cylindrata (Japan waters). Pharm: Antifungal (Mortierella ramanniana, 160 μg/disk). Ref: H. Li, et al, JNP, 1996, 59, 163

95

1.6 Linear Polypeptides

O Br

O

H N

H

N H O

O N

OH O

H N

N H

N H

O

O

H N NH

H2N

NH2

O

O S O

NH

H N

N H

O

O

O H OH

H N

N

NH2 O

O

N H

255 Kendarimide A Type: Linear polypeptides. C83H134N14O15S2 Powder, [α]D25 = −273° (c = 0.3, MeOH). Source: Sponge Haliclona sp. Pharm: Modulator of multidrug resistance in tumour cells. Ref: S. Aoki, et al, Tetrahedron, 2004, 60, 7053│N. Kotoku, et al, Heterocycles, 2005, 65, 563 O

O N

O N

N O

N

O

O

S

H O

N

H O HN

N O

OH

N O

S

N

N

H

N

N O

O

H H N

N

O

O

256 Koshikamide A2 Type: Linear polypeptides. C72H112N16O16 Amorph. solid, [α]D24 = −130° (c = 0.1, MeOH). Source: Lithistid sponge Theonella sp. (off Shimo-koshiki-jima Island, Kagoshima, Japan). Pharm: Cytotoxic (P388, IC50 = 4.6 μmol/L). Ref: T. Araki, et al, Biosci., Biotechnol., Biochem., 2005, 69, 1318│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

96

1 Peptides

O O

HO NH2 H N

O N

O

N H

O

NH HN

O

H

NH2

N H

O N

N

O O

O

H

N

NH2 O N

O N

N

O

O

O

N H

257 Neopetrosiamide A Type: Linear polypeptides. C129H183N35O39S7 Glass, [α]D = −65.2° (c = 4.2, MeOH). Source: Sponge Neopetrosia sp. Pharm: Inhibits amoeboid invasion of hmn tumour cells (6 μg/mL, having potential to be cell biology tools that can be enlisted to find drug targets for inhibiting amoeboid invasion of tumor cells). Ref: D. E. Williams, et al, Org. Lett., 2005, 7, 4173 O H 2N

O

H N

N H

O

H

N H

N

O

O

H N

O

H N

H N

O

O N H O

NH

S

S

O

S

S

NH O NH O

–

O

O

+

S

OH N H

HN

O O O N H

N H O

O

OH H N

N H O

O O N H H HO

HO H N

O

O

N H

OH O

HN

O O

OH NH2

S

O

O

S

O

H N

N H

O

O

H N

NH2

NH

H N O

NH HN

H

NH HN

NH2

N

1.7 Simple Cyclic Peptides

97

258 Neopetrosiamide B Type: Linear polypeptides. C129H183N35O39S7 Glass. Source: Sponge Neopetrosia sp. Pharm: Inhibits amoeboid invasion of hmn tumour cells (6 μg/mL, having potential to be cell biology tools that can be enlisted to find drug targets for inhibiting amoeboid invasion of tumor cells). Ref: D. E. Williams, et al, Org. Lett., 2005, 7, 4173

O H 2N

N H

O

H N

O

H

N H

N

O

O

H N

O

H N

H N

O

O N H O

NH

S

S

O

S

S

NH O

S-epimer of Neopetrosiamide A

NH O

–

O

O

+

S

HN

N H

OH N H O O O

N H O

O

OH H N

N H

O HO H N

N HH HO

O

O

N H

HN

O OH

O

O

OH O

S O

S

O

H N

N H

O

O

H N

O NH2 H O

NH2

NH

H N O

NH HN

N

NH HN

NH2

1.7 Simple Cyclic Peptides 259 Aciculitin A Type: Simple cyclic peptides. C61H86N14O21 Pale yellow powder, [α]D = −35° (c = 0.27, CH3CN/H2O 1:1). Source: Lithistid sponge Aciculites orientalis (Philippines). Pharm: Antifungal (standard disk assay, Candida albicans, 2.5 μg/disk); cytotoxic (HCT116, IC50 = 0.5 μg/mL). Ref: C. A. Bewley, et al, JACS, 1996, 118, 4314

98

1 Peptides

NH2 O

OH H N

HN

O

N H

O

O

NH

HO

O

HO HO O

O

HO

N

OH

O O

HN

NH

N H

O

O

NH2

N H

O H N O

OH

HN N H

O

260 Aciculitin B Type: Simple cyclic peptides. C62H88N14O21 [α]D = −37° (c = 0.35, CH3CN/H2O 1:1). Source: Lithistid sponge Aciculites orientalis (Philippines). Pharm: Antifungal (standard disk assay, Candida albicans, 2.5 μg/disk); cytotoxic (HCT116, IC50 = 0.5 μg/mL) Ref: C. A. Bewley, et al, JACS, 1996, 118, 4314 NH2 O

OH H N HN O

N H

O O

O O

NH

N H

O

OH

HO O

HO

HN

NH2

HO

NH

HO N

O

O

N H

O H N O

O HN

N H

OH

O

261 Aciculitin C Type: Simple cyclic peptides. C63H90N14O21 [α]D = −34° (c = 0.27, CH3CN/H2O 1:1). Source: Lithistid sponge Aciculites orientalis (Philippines). Pharm: Antifungal (standard disk assay, Candida albicans, 2.5 μg/disk); cytotoxic (HCT116, IC50 = 0.5 μg/mL) Ref: C. A. Bewley, et al, JACS, 1996, 118, 4314

1.7 Simple Cyclic Peptides

99

NH2

O

OH H N O

N H

O O

HN

NH

HO

O

O O

HN N H N H

O

NH2

OH

HO O

HO

N

O

HO

NH

O H N

O HN

N H

O

OH

O

262 (ADMAdda5)Microcystin LHar Type: Simple cyclic peptides. C51H76N10O13 Source: Cyanobacterium Nostoc sp. 152. Pharm: Hepatotoxin. Ref: K. Sivonen, et al, Appl. Environ. Microbiol., 1990, 56, 2650│ M. Namikoshi, et al, JOC, 1990, 55, 6135; 1992, 57, 866 O

COOH O

N

HN O

O

O NH

H N

HN

O H N

O

NH

H

H N O

COOH

O

NH2

263 (ADMAdda5)Microcystin LR Type: Simple cyclic peptides. C50H74N10O13 Source: Cyanobacterium Nostoc sp. 152. Pharm: Hepatotoxin. Ref: K. Sivonen, et al, Appl. Environ. Microbiol., 1990, 56, 2650│ M. Namikoshi, et al, JOC, 1990, 55, 6135; 1992, 57, 866 O

COOH O

N

HN O

O NH NH H 2N

O N H

NH

O O H N

HN

H N O

COOH

O

100

1 Peptides

264 (D-Asp,ADMAdda5)Microcystin LR Type: Simple cyclic peptides. C49H72N10O13 Source: Cyanobacterium Nostoc sp. 152. Pharm: Hepatotoxin. Ref: K. Sivonen, et al, Appl. Environ. Microbiol., 1990, 56, 2650│ M. Namikoshi, et al, JOC, 1990, 55, 6135; 1992, 57, 866 O

COOH O

N

HN O

O NH NH

O

H 2N

O H N

HN

H N O

N H

NH

O

COOH

O

265 Aspergillipeptide C Type: Simple cyclic peptides. C26H36N4O8 Source: Marine-derived fungus Aspergillus sp. from gorgonian Melitodes squamata (Sanya, Hainan, China). Pharm: Antifoulant (inhibits Bugula neritina larvae settlement, strong). Ref: J. Bao, et al, Tetrahedron, 2013, 69, 2113 O HN

H N

O O O O NH

N H

O

19E

OH OH

266 Asperterrestide A Type: Simple cyclic peptides. C26H32N4O5 Yellowish amorphous powder, [α]D30 = −13° (c = 0.03, MeOH). Source: Marine-derived fungus Aspergillus terreus SCSGAF016. Pharm: Antiviral (influenza a viral, H1N1, IC50 = 15 μmol/L; H3N2, IC50 = 8.1 μmol/L); cytotoxic (U937, IC50 = 6.4 μmol/L, Molt4, IC50 = 6.2 μmol/L). Ref: F. He, et al, JNP, 2013, 76, 1182 O O N H NH

NH N

O S

O OH

1.7 Simple Cyclic Peptides

101

267 Aspochracin Type: Simple cyclic peptides. C23H36N4O4 Pale yellow cryst., [α]D23 = −76° (c = 1, MeOH). Source: Marine-derived fungus Aspergillus sclerotiorum sp. 080903f04 from sponge Mycale sp. (Japan waters). Pharm: Insecticide; toxic. Ref: R. Myokei, et al, Tet. Lett., 1969, 10, 695│H. J. Somerville, et al, Acad. Sci., 1973, 217, 93│ K. Motohashi, et al, Biosci., Biotechnol., Biochem., 2009, 73, 1898 O NH O

N

O

N HN O

268 Axinastatin 1 Type: Simple cyclic peptides. C38H56N8O8 Cryst. (CH2Cl2), mp 283–287 °C (dec), [α]D = −162° (c = 0.1, MeOH). Source: Sponges Axinella sp., Pseudaxinyssa sp. and Pseudaxinella sp. Pharm: Cytotoxic; antimicrobial. Ref: G. R. Pettit, et al, JMC, 1991, 34, 3339; 1994, 37, 1165│F. Kong, et al, Tet. Lett., 1992, 33, 3269│R. Fernandez, et al, Tet. Lett., 1992, 33, 6017│G. R. Pettit, et al, JMC, 1994, 37, 1165│R. K. Konat, et al, Liebigs Ann., 1995, 765│W. Qi, et al, Huaxue Xuebao, 2007, 65, 233 H2N

O

O

N N H

HN

O O

NH

O

O

O

NH

N H

N O

269 Axinastatin 2 Type: Simple cyclic peptides. C39H58N8O8 mp 280–282 °C, [α]D = −153° (c = 0.17, MeOH). Source: Sponge Axinella sp. (Comoros and Palau). Pharm: Cytotoxic (OVCAR-3, GI50 = 0.058 μg/mL; SF295, GI50 = 0.35 μg/mL; A498, GI50 = 0.38 μg/mL; NCI-H460, GI50 = 0.19 μg/mL; KM20L2, GI50 = 0.23 μg/mL; SK-MEL-5, GI50 = 0.068 μg/mL). Ref: G. R. Pettit, et al, JMC, 1994, 37, 1165

102

1 Peptides

O H 2N O

O

N

N H

NH O

O

H N O

H N

N

H N O

O

270 Axinastatin 3 Type: Simple cyclic peptides. C40H60N8O8 mp 291–294 °C, [α]D = −185° (c = 0.21, MeOH). Source: Sponge Axinella sp. (Comoros and Palau). Pharm: Cytotoxic (OVCAR-3, GI50 = 0.0072 μg/mL; SF295, GI50 = 0.18 μg/mL; A498, GI50 = 0.11 μg/mL; NCI-H460, GI50 = 0.033 μg/mL; KM20L2, GI50 = 0.055 μg/mL; SK-MEL-5, GI50 = 0.012 μg/mL). Ref: G. R. Pettit, et al, JMC, 1994, 37, 1165 O H 2N O

O

NH O

N

N H

H N

O

O H N

H N

N

O

O

271 Axinastatin 4 Type: Simple cyclic peptides. C42H62N8O8 Amorphous solid, mp 201–206 °C, [α]D25 = −92.8° (c = 0.5, MeOH). Source: Sponge Axinella cf. carteri (Comoros Is.). Pharm: Cytotoxic. Ref: G. R. Pettit, et al, Heterocycles, 1993, 35, 711│O. Mechnich, et al, Helv. Chim. Acta, 1997, 80, 1338│R. B. Bates, et al, JNP, 1998, 61, 405 OH

O

O

NH H N

N

N H O

O

H

H N

O

H N

H N O

O

N H

1.7 Simple Cyclic Peptides

103

272 Axinastatin 5 Hymenamide G Type: Simple cyclic peptides. C47H72N8O9 Amorph. solid, [α]D17 = −127° (c = 0.97, MeOH). Source: Sponges Stylissa flabelliformis (Maldives, 1995) and Axinella cf. carteri. Pharm: Cytotoxic (interesting and valuable cancer cell growth inhibitor: P388, GI50 = 1.9 μg/mL; NCI-H460, GI50 = 0.82 μg/mL; KM20L2, GI50 = 0.28 μg/mL; DU145, GI50 = 0.87 μg/mL; BXPC3, GI50 = 0.68 μg/mL; MCF7, GI50 = 1.4 μg/mL; SF268, GI50 = 1.8 μg/mL). Ref: G. R. Pettit, et al, JNP 2008, 71, 438

N

N

HN O O

HN

O

O

OH

NH

O

O

O

O

NH

N H

N

273 Axinellin A Type: Simple cyclic peptides. C42H56N8O9 Amorph. solid, [α]D = −98.2° (c = 0.003, MeOH). Source: Sponge Axinella carteri (Vanuatu). Pharm: Cytotoxic (NSCLC-N6, IC50 = 3.0 μg/mL). Ref: A. Randazzo, et al, EurJOC, 1998, 2659 Ph

O

NH O

N

N H H N

OH Ph

O O N H

O

NH

O O

O NH2

N

274 Axinellin B Type: Simple cyclic peptides. C50H67N9O9 Amorph. solid, [α]D = +50° (c = 0.001, MeOH). Source: Sponge Axinella carteri (Vanuatu). Pharm: Cytotoxic (NSCLC-N6, IC50 = 7.3 μg/mL). Ref: A. Randazzo, et al, EurJOC, 1998, 2659

104

1 Peptides

H N H N

N O

O

NH

O

O H N

N

O

N

O O HN

N H

OH

O

275 Azumamide A Type: Simple cyclic peptides. C27H39N5O5 Amorph. solid, [α]D23 = +33° (c = 0.1, MeOH). Source: Sponge Mycale izuensis. Pharm: Histone deacetylase inhibitor; antineoplastic. Ref: Y. Nakao, et al, Angew. Chem., Int. Ed., 2006, 45, 7553 O O

N H

NH H N

HN O

O H2 N

O

276 Azumamide E Type: Simple cyclic peptides. C27H38N4O6 Amorph. yellow solid, [α]D21 = +53° (c = 0.06, MeOH). Source: Sponge Mycale izuensis. Pharm: Histone deacetylase inhibitor (IC50 = 50–80 nmol/L, MMOA: selective inhibition of isoforms 1, 2, and 3). Ref: N. Maulucci, et al, JACS, 2007, 129, 3007 O O

N H

NH H N

HN O

O HO

O

1.7 Simple Cyclic Peptides

105

277 Callyaerin A Type: Simple cyclic peptides. C69H108N14O14 White amorph. powder, [α]D = −80° (c = 0.12, MeOH). Source: Sponge Callyspongia aerizusa (Ambon, Indonesia). Pharm: Cytotoxic (L5178Y, GI50 = 3.61 μmol/L); antibacterial (5–10 μL: Staphylococcus aureus, IZD = 9–9 mm; Bacillus subtilis, IZD = 0–0 mm; Escherichia coli, IZD = 10–15 mm); antifungal (5–10 μL, Candida albicans, IZD = 25–20 mm). Ref: S. R. M. Ibrahim, et al, BoMC, 2010, 18, 4947

O

H N

HN

O

H N O

N

H N

N O

O

O

O

NH

NH2

O

O

HN

N

O

O

NH

O O

N

N H

N H

HO

278 Callyaerin B Type: Simple cyclic peptides. C65H109N13O13 White amorph. powder, [α]D = −89° (c = 0.2, MeOH). Source: Sponge Callyspongia aerizusa (Ambon, Indonesia). Pharm: Cytotoxic (L5178Y, GI50 = 4.14 μmol/L; Hela, GI50 > 8 μmol/L; PC12, GI50 > 8 μmol/L); antibacterial (5–10 μL: Staphylococcus aureus, IZD = 11–11 mm; Bacillus subtilis, IZD = 0–0 mm; Escherichia coli, IZD = 7–10 mm); antifungal (5–10 μL, Candida albicans, IZD = 15–15 mm); toxic (brine shrimp assay, 20 μg/mL, mortality = 15%, 50 μg/mL, mortality = 35%). Ref: S. R. M. Ibrahim, et al, BoMC, 2010, 18, 4947

O

H N

HN

O

H N O

N

H N

O

N O

O O

NH

O

O

NH2 N

HO

N

O

O O N H

N H

NH

106

1 Peptides

279 Callyaerin C Type: Simple cyclic peptides. C63H93N15O13 White amorph. powder, [α]D = −52° (c = 0.15, MeOH). Source: Sponge Callyspongia aerizusa (Ambon, Indonesia). Pharm: Cytotoxic (L5178Y, GI50 = 2.92 μmol/L); antibacterial (5–10 μL: Staphylococcus aureus, IZD = 0–0 mm; Bacillus subtilis, IZD = 7–10 mm; Escherichia coli, IZD = 0–0 mm); antifungal (5–10μL, Candida albicans, IZD = 0–0 mm). Ref: S. R. M. Ibrahim, et al, BoMC, 2010, 18, 4947 O

H N

HN

O

H N O

N

H N

O O

N NH

N

O

O

HN O

N

O O

O

N H

N H

O

N

N H

NH2 HO

280 Callyaerin D Type: Simple cyclic peptides. C68H105N15O15 White amorph. powder, [α]D = −49° (c = 0.2, MeOH). Source: Sponge Callyspongia aerizusa (Ambon, Indonesia). Pharm: Cytotoxic (L5178Y, GI50 = 3.03 μmol/L); antibacterial (5–10 μL: Staphylococcus aureus, IZD = 0–0 mm; Bacillus subtilis, IZD = 12–12 mm; Escherichia coli, IZD = 0–0 mm); antifungal (5–10 μL, Candida albicans, IZD = 0–7 mm). Ref: S. R. M. Ibrahim, et al, BoMC, 2010, 18, 4947

O

H N

HN

O

H N O

NH O

NH2 H N O

N

O O

O

O

O O

N

OH

N

H N

N H

NH

O N

O N H

NH2 O

281 Callyaerin E Type: Simple cyclic peptides. C66H95N13O12 White amorph. powder, [α]D = −68° (c = 0.25, MeOH). Source: Sponge Callyspongia aerizusa (Ambon, Indonesia).

1.7 Simple Cyclic Peptides

107

Pharm: Cytotoxic (L5178Y, GI50 = 0.39 μmol/L; Hela, GI50 = 3.4 μmol/L; PC12, GI50 = 3.8 μmol/L); antibacterial (5–10 μL: Staphylococcus aureus, IZD = 9–10 mm; Bacillus subtilis, IZD = 15–17 mm; Escherichia coli, IZD = 9–11 mm); antifungal (5–10 μL, Candida albicans, IZD = 20–20 mm); toxic (brine shrimp assay, 20 μg/mL, mortality = 45%, 50 μg/mL, mortality = 70%). Ref: S. R. M. Ibrahim, et al, BoMC, 2010, 18, 4947 O

H N

HN

O

H N O

N

H N

O O

N

N

O O

O NH2 HN

NH

O

O

O

N H

O

N

N H

282 Callyaerin F Type: Simple cyclic peptides. C58H83N11O10 White amorph. powder, [α]D = −32° (c = 0.15, MeOH). Source: Sponge Callyspongia aerizusa (Ambon, Indonesia). Pharm: Cytotoxic (L5178Y, GI50 > 9 μmol/L; Hela, GI50 > 9 μmol/L; PC12, GI50 > 9 μmol/L); antibacterial (5–10 μL: Staphylococcus aureus, IZD = 0–7 mm; Bacillus subtilis, IZD = 0–9 mm; Escherichia coli, IZD = 0–0 mm); antifungal (5–10 μL, Candida albicans, IZD = 0–0 mm). Ref: S. R. M. Ibrahim, et al, BoMC, 2010, 18, 4947

H N

O

N O

O

H N

NH

N O

O

O

O

HN H 2N

O

NH O

NH

N

O N H

283 Callyaerin G Type: Simple cyclic peptides. C69H91N13O12 Amorph. powder, mp 237 °C, [α]D = −55° (c = 0.3, MeOH). Source: Sponge Callyspongia aerizusa Pharm: Cytotoxic. Ref: S. R. M. Ibrahim, et al, ARKIVOC, 2008, xii, 164

108

1 Peptides

H N H

H N

N

O O

N

H

O

O

O

O H N

NH

NH O N O H

O

HN

O

H N

N H

NH2

N H

O

O

284 Callyaerin H Type: Simple cyclic peptides. C54H81N11O10 White amorph. powder, [α]D = −93° (c = 0.3, MeOH). Source: Sponge Callyspongia aerizusa (Ambon, Indonesia). Pharm: Cytotoxic (L5178Y, GI50 = 0.48 μmol/L); toxic (brine shrimp assay, 20 μg/mL, mortality = 30%, 50 μg/mL, mortality = 55%). Ref: S. R. M. Ibrahim, et al, BoMC, 2010, 18, 4947

O H 2N

H N

O

H N O

N

H N

O O

N

N

O O

NH O N

O N H

O N H

285 Chloropullularin E Type: Simple cyclic peptides. C43H58ClN5O7 Source: Mangrove-derived fungus Bionectria ochroleuca from mangrove Sonneratia caseolaris (leaf, Hainan, China). Pharm: Cytotoxic (L5178Y, 10 μg/mL, Survival Rate = 15.6%, EC50 = 5.60 μg/mL, control Kahalalide F, EC50 = 6.40 μg/mL). Ref: W. Ebrahim, et al, Mar. Drugs, 2012, 10, 1081

1.7 Simple Cyclic Peptides

109

O Cl N

HN O N

O

O O

O O N

N H

286 Clonostachysin A Type: Simple cyclic peptides. C53H87N9O10 Powder, [α]D25 = −97° (c = 0.06, MeOH). Source: Marine-derived fungus Clonostachys rogersoniana HJK9 from an unidentified sponge. Pharm: Selectively inhibitory effect (dinoflagellate Prorocentrum micans, 30 μmol/L; no effect on other microalgae and bacteria at 100 μmol/L). Ref: K. Adachi, et al, J. Antibiot., 2005, 58, 145│ M. Saleem, et al, NPR, 2007, 24, 1142 (rev) O

N O N

O

H N

O N

O

N

O

N

O

O N

N

N O

O

H

287 Clonostachysin B Type: Simple cyclic peptides. C54H89N9O10 Powder, [α]D25 = −87° (c = 0.03, MeOH). Source: Marine-derived fungus Clonostachys rogersoniana HJK9 from an unidentified sponge. Pharm: Selectively inhibitory effect (dinoflagellate Prorocentrum micans, 30 μmol/L; no effect on other microalgae and bacteria at 100 μmol/L). Ref: M. Saleem, et al, NPR, 2007, 24, 1142 (rev)

110

1 Peptides

O

N O N

O

H N

O

O

N

O

N

O

O N

N

N

N

H

O

O

288 Cocosamide A Type: Simple cyclic peptides. C42H57N5O7 White solid, [α]D25 = −77.7° (c = 0.12, MeOH). Source: Cyanobacterium Lyngbya majuscula (Cocos Lagoon, Guam). Pharm: Cytotoxic (MCF7, IC50 = 30 μmol/L; HT29, IC50 = 24 μmol/L). Ref: S. P. Gunasekera, et al, JNP, 2011, 74, 871

O N

N NH

O

O

O

N

O

O O

N H

289 Cocosamide B Type: Simple cyclic peptides. C42H57N5O7 White solid, [α]D25 = −103° (c = 0.18, MeOH). Source: Cyanobacterium Lyngbya majuscula (Cocos Lagoon, Guam). Pharm: Cytotoxic (MCF7, IC50 = 39 μmol/L; HT29, IC50 = 11 μmol/L). Ref: S. P. Gunasekera, et al, JNP, 2011, 74, 871

O N

N O

NH

O O

O

O N H

O N

1.7 Simple Cyclic Peptides

111

290 Cordyheptapeptide C Type: Simple cyclic peptides. C48H63N7O8 Source: Marine-derived fungus Acremonium persicinum (sediment, South China Sea). Pharm: Cytotoxic (HTCLs cells). Ref: Z. Chen, et al, JNP, 2012, 75, 1215 HO

O O

N NH

HN

NH

O

O N

N O

O

N

O

291 Cordyheptapeptide E Type: Simple cyclic peptides. C49H65N7O9 Source: Marine-derived fungus Acremonium persicinum (sediment, South China Sea). Pharm: Cytotoxic (HTCLs cells). Ref: Z. Chen, et al, JNP, 2012, 75, 1215 HO O O

N NH

O

HN

NH

O N

N O

O

N

O OH

292 Cotteslosin B Type: Simple cyclic peptides. C35H47N5O7 Source: Marine-derived fungus Aspergillus versicolor MST-MF495 (from beach sand, Australia). Pharm: Cytotoxic (several cancer cell lines, weak). Ref: L. J. Fremlin, et al, JNP, 2009, 72, 666

112

1 Peptides

OH O O

N O

NH O

HN H N

N H

O

OH

293 Cupolamide A Type: Simple cyclic peptides. C42H67N11O14S Amorph. solid (Na salt), [α]D = −34.28° (c = 1.94, MeOH) (Na salt). Source: Lithistid sponge Theonella cupola (Indonesia; Okinawa). Pharm: Cytotoxic (P388, IC50 = 7.5 μg/mL). Ref: L. S. Bonnington, et al, JOC, 1997, 62, 7765 NH H 2N

N H

H N

HN O

O

O

HN HO

O N

O

O S OH O

O

O

NH

NH

H N

O

N H

O

OH

294 Cyclocinamide A Type: Simple cyclic peptides. C29H38BrClN9O8 Amorph. solid, [α]D = +29° (c = 0.10, MeOH). Source: Sponges Psammocinia sp. (Papua New Guinea) and Psammocinia aff. bulbosa. Pharm: Cytotoxic (50 μg/disk, displayed zone sizes = 0/500/0/0 for L1210/C38/M17-Adr/CX1) (Clark, 1997); cytotoxic (L1210, IC50 = 50 μg/disk, M17-Adr, IC50 = 500 μg/disk, CX1, IC50 = 500 μg/disk, C38). Ref: W. D. Clark, et al, JACS, 1997, 119, 9285│P. A. Grieco et al, Tet. Lett., 1998, 39, 8925│S. J. Robinson, et al, JNP, 2007, 70, 1002 H N Br O

O HO

NH H N

O

H N

7

N H

O

HN

O

N 36

Cl

14

O

N H

NH2

1.7 Simple Cyclic Peptides

113

295 Cyclo(isoleucylprolylleucylprolyl) Antibiotic MK 349A Type: Simple cyclic peptides. C22H36N4O4 Gum, [α]D25 = −41.3° (c = 0.12, MeOH). Source: Marine-derived bacterium Nocardiopsis sp. (psychrophilic, cold water, 3000 m, Pacific sediments). Pharm: Cytotoxic (K562, crude extract LC50 < 0.05 μg/mL; pure compound, inactive). Ref: J. Shin, et al, JNP, 2003, 66, 883│ M.D. Lebar, et al, NPR, 2007, 24, 774 (rev)

N H N

O O OO

N H

N

296 Cyclomarin A Marinovir Type: Simple cyclic peptides. C56H82N8O11 Cryst. (Me2CO/Et2O), [α]D20 = −51.7° (c = 0.48, CHCl3). Source: Marine-derived streptomycete Streptomyces sp. CNB-982 (Mission Bay, San Diego, CA), marine-derived bacterium Salinispora arenicola CNS-205. Pharm: Anti-inflammatory (in vitro, phorbol ester (PMA)-induced mouse ear edema assay, 50 μg/ear, InRt = 92%, control Indomethacin, InRt = 72%; in vivo, 30 mg/kg ip administration, InRt = 45%, indicating cyclomarin A may be a potential drug candidate); antiviral; cytotoxic (a panel of hmn cancer cell lines in vitro, IC50 = 2.6 μmol/L). Ref: M. K. Renner, et al, JACS, 1999, 121, 11273│A. W. Schultz, et al, JACS, 2008, 130, 4507

N 13

HO

3

2

18

O

N H

O

N 50

HO

H

H N

O

53

HN

O

O

H N

O

N

O

HN O

H MeO

297 (all-L)-Cyclo(Pro-Val)2 Type: Simple cyclic peptides. C20H32N4O4 Source: Ascidian Cystodytes dellechiajei. Pharm: Cytotoxic (L1210, ID50 = 1.5 μg/mL). Ref: J. -M. Aracil, et al, Tet. Lett., 1991, 32, 2609

114

1 Peptides

N O O O O

HN

NH

N

298 Cyclotheonamide A Type: Simple cyclic peptides. C36H45N9O8 [α]D23 = −13° (c = 0.2, MeOH). Source: Lithistid sponge Theonella sp. Pharm: Thrombin inhibitor (potent). Ref: N. Fusetani, et al, JACS, 1990, 112, 7053│ M. Hagihara, et al, JACS, 1992, 114, 6570│P. Wiplf, et al, JOC, 1993, 58, 5592│B. E. Maryanoff, et al, JACS, 1995, 117, 1225│ H. M. M. Bastiaans, et al, Tet. Lett., 1995, 36, 5963 OH 5

O N H O

HN NH H 2N

H N

O

H N

4

O

O O N

O N H

N H

299 Cyclotheonamide B Type: Simple cyclic peptides. C37H47N9O8 [α]D23 = −13.5° (c = 0.2, MeOH). Source: Lithistid sponge Theonella swinhoei. Pharm: Thrombin inhibitor (potent). Ref: N. Fusetani, et al, JACS, 1990, 112, 7053│ M. Hagihara, et al, JACS, 1992, 114, 6570│J. Deng, et al, Angew. Chem., Int. Ed. Engl., 1994, 33, 1729│B. E. Maryanoff, et al, JACS, 1995, 117, 1225│H. M. M. Bastiaans, et al, Tet. Lett., 1995, 36, 5963│ J. Deng, et al, Tetrahedron, Lett, 1996, 37, 2261 OH O

HN NH H 2N

O N H

H N

N H O H N

O

O O N

O N H

1.7 Simple Cyclic Peptides

115

300 Cyclotheonamide C Type: Simple cyclic peptides. C36H43N9O8 Amorph. yellow solid, [α]D23 = +42.4° (c = 1, MeOH). Source: Lithistid sponge Theonella swinhoei (Japan waters). Pharm: Thrombin inhibitor. Ref: Y. Nakao, et al, Bioorg. Med. Chem., 1995, 3, 1115 HO

O

HN HN

O O

NH

O

H N

O

O

NH N

O

NH NH2

N H

301 Cyclotheonamide D Type: Simple cyclic peptides. C33H47N9O8 Amorph. solid, [α]D23 = −16.7° (c = 0.27, MeOH). Source: Lithistid sponge Theonella swinhoei (Japan waters). Pharm: Thrombin inhibitor. Ref: Y. Nakao, et al, Bioorg. Med. Chem., 1995, 3, 1115 HO

O

HN HN

O O

NH H N

O

O

O

NH N

O

NH N H

NH2

302 Cyclotheonamide E Type: Simple cyclic peptides. C43H58N10O9 Amorph. solid, [α]D23 = −17.6° (c = 0.07, MeOH). Source: Lithistid sponge Theonella swinhoei, sponge Ircinia sp. Pharm: Thrombin inhibitor. Ref: Y. Nakoa, et al, Bioorg. Med. Chem., 1995, 3, 1115

116

1 Peptides

OH 34

H

O

HN HN

O O

H N

O

O

O

NH

N H

N O

H N O

NH NH2

N H

303 Cyclotheonamide E2 Type: Simple cyclic peptides. C42H56N10O9 Amorph. pale brown solid, [α]D26 = −37.3° (c = 0.1, MeOH). Source: Lithistid sponge Theonella sp. (Japan waters). Pharm: Serine proteases inhibitor. Ref: Y. Nakoa, et al, JNP, 1998, 61, 667│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev) OH 34

H

O

HN HN

O O O

O

NH H N

N O N H

O N H

H N O

NH NH2

304 Cyclotheonamide E3 Type: Simple cyclic peptides. C40H60N10O9 Amorph. pale brown solid, [α]D26 = −40.2° (c = 0.1, MeOH). Source: Lithistid sponge Theonella sp. (Japan waters). Pharm: Serine proteases inhibitor. Ref: Y. Nakoa, et al, JNP, 1998, 61, 667│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

1.7 Simple Cyclic Peptides

117

OH 34

H

O

HN HN

O O

H N

O

O

O

NH

N O

H N

N H

O

NH NH2

N H

305 Dihydrocyclotheonamide A Type: Simple cyclic peptides. C36H47N9O8 Amorph. solid, [α]D29 = +37° (c = 0.25, MeOH). Source: Lithistid sponge Theonella swinhoei (Japan waters). Pharm: Serine protease inhibitor; thrombin inhibitor (IC50 = 0.33 μmol/L); trypsin inhibitor (IC50 = 6.7 μmol/L). Ref: Y. Nakao, et al, ACS, 1999, 121, 2425│R. Samy, et al, JOC, 1999, 64, 2711│T. Hu, et al, JOC, 1999, 64, 3000│S. M. Bauer, et al, JACS, 1999, 121, 6355 OH

O

HN HN

O O

O

NH

O H N

HO

N H

O

H

N

NH N H

NH2

306 Discodermin A Type: Simple cyclic peptides. C77H116N20O22S mp 226–227 °C, [α]D22 = −6.3° (c = 0.7, MeOH). Source: Lithistid sponge Discodermia kiiensis. Pharm: Antimicrobial; tumour promotion activity inhibitor; PLA2 inhibitor; inhibits development of starfish embryo (starfish Asterina pectinifera, 5 μg/mL). Ref: S. Matsunaga, et al, Tet. Lett. 1984, 25, 5165│S. Matsunaga, et al, Tet. Lett., 1985, 26, 855│S. Matsunaga, et al, JNP, 1985, 48, 236│G. Ryu. et al, Tet. Lett., 1994, 35, 8251│G. Ryu. et al, Tetrahedron, 1994, 50, 13409

118

1 Peptides

O

NH O N H

N

O

H N

N H

O

O

O

H N

HN

H N

O

NH

O

O

NH

H2N

O

O

O O

N H

O

OH

S

N N

H

N H

O

O O

N H

O NH2

NH H2N

O

O

N H H

HO

307 Discodermin B Type: Simple cyclic peptides. C76H114N20O22S mp 217–219 °C, [α]D23 = −3.2° (c = 1.0, MeOH). Source: Lithistid sponge Discodermia kiiensis. Pharm: Antifungal (Mortierella rumunniunus); antibacterial (Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis and Mycobacterium smegmatis); PLA2 inhibitor; inhibits development of starfish embryo (starfish Asterina pectinifera, 50 μg/mL). Ref: S. Matsunaga, et al, Tet. Lett., 1985, 26, 855│G. Ryu. et al, Tet. Lett., 1994, 35, 8251│G. Ryu. et al, Tetrahedron, 1994, 50, 13409

O

NH O

N

H N

N H

O

O H N

O N H

H N

O

H2N

O

O

OH O O

N H

O

HN

S

O

NH

O

O

NH

N N

N H

H

O

O O O

O

N H

NH2 HO

NH H2N

O

N H H

308 Discodermin C Type: Simple cyclic peptides. C76H114N20O22S mp 222–224 °C, [α]D23 = −6.6° (c = 1.0, MeOH). Source: Lithistid sponge Discodermia kiiensis. Pharm: Antifungal (Mortierella

1.7 Simple Cyclic Peptides

119

rumunniunus); antibacterial (Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis and Mycobacterium smegmatis); PLA2 inhibitor; inhibits development of starfish embryo (starfish Asterina pectinifera, 50 μg/mL). Ref: S. Matsunaga, et al, Tet. Lett., 1985, 26, 855│G. Ryu. et al, Tet. Lett., 1994, 35, 8251│G. Ryu. et al, Tetrahedron, 1994, 50, 13409

O

NH O

N

H N

N H

O

H 2N

O

O

O O

N H

O

HN

OH

S

O

H N

N H

O

O H N

O

NH

O

O

NH

N N

H

N H

O

O O O

O

N H

NH2 HO

NH H2 N

O

N H H

309 Discodermin D Type: Simple cyclic peptides. C75H112N20O22S mp 215–219 °C, [α]D23 = −4.7° (c = 1, MeOH). Source: Lithistid sponge Discodermia kiiensis. Pharm: Antifungal (Mortierella rumunniunus); antibacterial (Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis and Mycobacterium smegmatis); PLA2 inhibitor; inhibits development of starfish embryo (starfish Asterina pectinifera, 50 μg/mL). Ref: S. Matsunaga, et al, Tet. Lett., 1985, 26, 855│G. Ryu. et al, Tet. Lett., 1994, 35, 8251│G. Ryu. et al, Tetrahedron, 1994, 50, 13409

O

NH O

N

H N

N H

O

O H N

O N H

H N

O N H

H 2N

O

N H

O

HN

S

O

O

O O

NH

O

NH

OH

O N

N H

O O O O O

N NH2 H HO

N H H

NH H2N

O

120

1 Peptides

310 Discodermin E Type: Simple cyclic peptides. C76H116N20O23S Colorless solid, [α]D23 = −7.1° (c = 0.01, MeOH). Source: Lithistid sponge Discodermia kiiensis (Japan waters). Pharm: Cytotoxic (P388, IC50 = 0.02 μg/mL); inhibits the development of starfish. Ref: S. Matsunaga, et al, Tet. Lett., 1985, 26, 855│G. Ryu, et al, Tetrahedron, 1994, 50, 13409│G. Ryu, et al, Tet. Lett., 1994, 35, 8251 H 2N O O

N

O

H N

N H

H N

O

O

O

NH

O

O

NH

H 2N

O O

N H

O

HN

OH

S

O

H N

N H

O

O

O

N N

H

N H

O

O O O

O

N H

NH2 HO

NH H2N

O

N H H

311 Discodermin F Type: Simple cyclic peptides. C78H118N20O22S Amorph. solid, [α]D23 = −6.7° (c = 0.8, MeOH). Source: Lithistid sponge Discodermia kiiensis (Japan waters). Pharm: Cytotoxic; antimicrobial; toxic (Asterina pectinifera). Ref: S. Matsunaga, et al, Tet. Lett., 1985, 26, 855│G. Ryu, et al, Tetrahedron, 1994, 50, 13409

O

NH O

N

H N

N H

O

O H N

O N H

H N

O

H2N

O

O

O O

N H

O

HN

OH

S

O

NH

O

O

NH

N N

N H

H

O

O O

O NH2

N H

HO

O N H H

NH H2N

O

1.7 Simple Cyclic Peptides

121

312 Discodermin G Type: Simple cyclic peptides. C78H118N20O22S Amorph. solid, [α]D23 = −6.8° (c = 0.6, MeOH). Source: Lithistid sponge Discodermia kiiensis (Japan waters). Pharm: Cytotoxic; antimicrobial; toxic (Asterina pectinifera). Ref: S. Matsunaga, et al, Tet. Lett., 1985, 26, 855│G. Ryu, et al, Tetrahedron, 1994, 50, 13409

O

NH O

H N

N H

N

O

NH

O

O

NH

H 2N

O

O

OH O

N H

O

HN O

S

O

H N

N H

O

O H N

O

N N

H

N H

O

O O

O

N H

NH2

O

NH H2N

O

N H H

HO

313 Discodermin H Type: Simple cyclic peptides. C77H116N20O23S Amorph. solid, [α]D23 = −5.8° (c = 0.6, MeOH). Source: Lithistid sponge Discodermia kiiensis (Japan waters). Pharm: Cytotoxic; antimicrobial. Ref: S. Matsunaga, et al, Tet. Lett., 1985, 26, 855│G. Ryu, et al, Tetrahedron, 1994, 50, 13409

O

NH O

N

H N

N H

O

O H N

O N H

H N

O

H 2N

O

O

OH O O

N H

O

HN

S

O

NH

O

O

NH

N N

N H OH

H

O

O O O

O

N H

NH2 HO

N H H

NH H2N

O

122

1 Peptides

314 Dominicin Type: Simple cyclic peptides. C43H72N8O9 Prisms, mp 168–171 °C, [α]D25 = −118.7° (c = 7.8, MeOH). Source: Sponges Prosuberites laughlini (Aguadilla, Puerto Rico) and Eurypon laughlini. Pharm: Cytotoxic (NCIs one-dose 60-cell-line assay, 10 μmol/L, SR, InRt = 20%, UO-31, InRt = 68%). Ref: D. E. Williams, et al, JNP, 2005, 68, 327│J. Vicente, et al, Tet. Lett., 2009, 50, 4571

O

H N

N O N

O

OH N

O O N H

NH

HN

H N

O

O

O

315 Euryjanicin A Type: Simple cyclic peptides. C44H58N8O8 Cryst., mp 174–176 °C, [α]D20 = −18° (c = 1, CHCl3). Source: Sponge Prosuberites laughlini (Aguadilla, Puerto Rico). Pharm: Cytotoxic (NCIs one-dose 60-cell-line assay, 10 μmol/L, NCI-H522, InRt = 28%, UO-31, InRt = 27%). Ref: J. Vicente, et al, Tet. Lett., 2009, 50, 4571

OH

Ser

O

O

O

NH

N H

Phe

O

N H

O

Val Pro

N

Ile

NH

O Pro

O

NH Trp

N

N H

316 Homodolastatin 16 Type: Simple cyclic peptides. C48H72N6O10 Pale yellow oil, [α]D22 = −25° (c = 0.19, MeOH). Source: Cyanobacterium Lyngbya majuscula (Kenyan and Madagascar). Pharm: Cytotoxic (H460, moderate); cytotoxic (MTT assay, WHCO1, IC50 = 4.3 μg/mL;

1.7 Simple Cyclic Peptides

123

WHCO6, IC50 = 10.1 μg/mL; ME180, IC50 = 8.3 μg/mL). Ref: M. T. Davies-Coleman, et al, JNP 2003, 66, 712

O O

H N

N

N

O

O O

HN O

O

O O

H N

N

H

O

317 Hormothamnin A Type: Simple cyclic peptides. C60H97N11O14 Powder. Source: Cyanobacterium Hormothamnion enteromorphoides (Puerto Rico). Pharm: Cytotoxic. Ref: W. H. Gerwick, et al, Tetrahedron, 1992, 48, 2313│W. H. Gerwick, et al, Tetrahedron, 1992, 48, 5755 (corrigendum)

HO H N

H

O N H

N

Z

O O

NH

N H

H N

O

O O

H N

O

H N

OH

O

O N H

HN

H N

O O

HO

318 Hymenistatin 1 Type: Simple cyclic peptides. C47H72N8O9 Amorphous solid, mp 180–182 °C, [α]D = −8.6° (c = 1, CHCl3). Source: Sponges Hymeniacidon sp. (Okinawa) and Axinella carteri. Pharm: Cytotoxic. Ref: G. R. Pettit, et al, Can. J. Chem., 1990, 68, 708│ R. K. Konat, et al, Helv. Chim. Acta, 1993, 76, 1649

124

1 Peptides

N

N HN O O

HN

O

O

O

OH

NH

O O

O

NH N

N H

319 Kapakahine A Type: Simple cyclic peptides. C58H72N10O8 Amorph. solid, [α]D20 = −131° (c = 1, MeOH). Source: Sponge Cribrochalina olemda (Pohnpei I., Federated States of Micronesia). Pharm: Cytotoxic (P388, IC50 = 5.4 μg/mL); protein phosphatase 2A inhibitor (30 μmol/L (32 μg/mL), InRt = 15%); thrombin inhibitor, trypsin inhibitor, plasmin inhibitor, elastase inhibitor, papain inhibitor, ACE inhibitor. Ref: B. K. S. Yeung, et al, JOC, 1996, 61, 7168

O N H O

HN

O

N H

NH2 N

O O N

N H H

HO

H N O

O

N

H

N O

320 Kapakahine B Type: Simple cyclic peptides. C49H52N8O6 Amorph. solid, [α]D20 = −70° (c = 0.3, MeOH). Source: Sponge Cribrochalina olemda (Pohnpei I., Federated States of Micronesia). Pharm: Cytotoxic (P388, IC50 = 5.0 μg/mL). Ref: Y. Nakao, et al, JACS, 1995, 117, 8271│B. K. S. Yeung, et al, JOC, 1996, 61, 7168

1.7 Simple Cyclic Peptides

125

O NH

H N

NH2 O

O

HN

O N NH N

H

N

O

O

321 Kapakahine C Type: Simple cyclic peptides. C58H72N10O10 Amorph. solid, [α]D20 = −120° (c = 0.5, MeOH). Source: Sponge Cribrochalina olemda (Pohnpei I., Federated States of Micronesia). Pharm: Cytotoxic (P388, IC50 = 5.0 μg/mL). Ref: B. K. S. Yeung, et al, JOC, 1996, 61, 7168

O N H O

HN

O N

O

N H

4

N H

O N H H

HO

OH

H

5

N

H N O

O

N

H

N O

322 Kapakahine E Type: Simple cyclic peptides. C57H57N9O8 Source: Sponge Cribrochalina olemda. Pharm: Cytotoxic (P388). Ref: Y. Nakao, et al, Org. Lett., 2003, 5, 1387

126

1 Peptides

O N

O

O H

HO

NH2

H N

N

NH H N

O

N H

O

O

N

H

N O

323 Loloatin A Type: Simple cyclic peptides. C65H84N12O15 White powder, mp 229–232 °C, [α]D = −88° (EtOH). Source: An unidentified marine-derived bacterium MK-PNG-276A (cultures, Reefs off Loloata I., Papua New Guinea). Pharm: Antibacterial (MRSA, MIC = 4 μg/mL, VREF, MIC = 4 μg/mL, PRSP, MIC = 2 μg/mL). Ref: J. M. Gerard, et al, JNP, 1999, 62, 80 OH OH O

H N

HN

N H

O O O HO

HN

O

H N O O NH2

Ph O

N H H2N

O

H N O

N H

N

O NH

O

324 Loloatin B Type: Simple cyclic peptides. C67H85N13O14 White powder, mp 229–233 °C, [α]D = −80° (EtOH). Source: An unidentified marine-derived bacterium MK-PNG-276A (cultures, Reefs off Loloata I., Papua New Guinea). Pharm: Antibacterial (MRSA, MIC = 2 μg/mL, VREF, MIC = 2 μg/mL, PRSP, MIC = 1 μg/mL). Ref: J. M. Gerard, et al, Tet. Lett., 1996, 37, 7201│J. M. Gerard, et al, JNP, 1999, 62, 80

1.7 Simple Cyclic Peptides

127

OH

HN

O

H N

HN

N H

O O O

O

HN

O O NH2

Ph O

HO

H N

N H H2N

O

O

H N

NH

N H

O

N

O

325 Loloatin C Type: Simple cyclic peptides. C69H86N14O14 White powder, mp 239–243 °C, [α]D = −76° (EtOH). Source: An unidentified marine-derived bacterium MK-PNG -276A (cultures, Reefs off Loloata I., Papua New Guinea). Pharm: Antibacterial (MRSA, MIC = 0.5 μg/mL, VREF, MIC = 2 μg/mL, PRSP, MIC < 0.25 μg/mL); antibacterial (gram-negative bacterium Escherichia coli). Ref: J. M. Gerard, et al, JNP, 1999, 62, 80 OH

O

H N

HN

N H

O O N H

O HO

HN

O

H N O NH2 O

Ph O

N H H 2N

O

H N O

O

N H

N

O NH

N H

326 Loloatin D Type: Simple cyclic peptides. C67H85N13O15 White powder. Source: An unidentified marine-derived bacterium MK-PNG-276A (cultures, Reefs off Loloata I., Papua New Guinea). Pharm: Antibacterial (MRSA, MIC = 8 μg/mL, VREF, MIC = 8 μg/mL, PRSP, MIC = 4 μg/mL). Ref: J. M. Gerard, et al, JNP, 1999, 62, 80

128

1 Peptides

OH

HN O

HO

N H

O

O

HN O

N H

O

H N

H N O NH2 O

Ph O

O

H N

N H H 2N

N H

O

N

O

OH

NH

O

327 Microcionamide A Type: Simple cyclic peptides. C43H70N8O7S2 Glass (TFA salt), [α]D = −36.5° (c = 0.27, MeOH) (TFA salt). Source: Sponge Thalysias abietina. Pharm: Cytotoxic (MCF7, IC50 = 125 nmol/L; SKBR3, IC50 = 98 nmol/L; control Doxorubicin, MCF7, IC50 = 257 nmol/L; SKBR3, IC50 = 33 nmol/L; to induce apoptosis within 24h in MCF7 at 5.7 μmol/L); antituberculosis (MABA assay, avirulent strain Mycobacterium tuberculosis H37Ra, MIC = 5.7 μmol/L; control Rifampicin, MIC = 1.52 nmol/L). Ref: R. A. Davis, et al, JOC, 2004, 69, 4170

O

H N H

H

O

HN

H O

NH

H N

O

36

N H

O S S H N H

O

N H

O

NH2

328 Microcionamide B Type: Simple cyclic peptides. C43H70N8O7S2 Glass (TFA salt), [α]D = −40.3° (c = 0.32, MeOH) (TFA salt). Source: Sponge Thalysias abietina. Pharm: Cytotoxic (MCF7, IC50 = 177 nmol/L; SKBR3, IC50 = 172 nmol/L; control Doxorubicin, MCF7, IC50 = 257 nmol/L; SKBR3, IC50 = 33 nmol/L; to induce apoptosis within 24h in MCF7 at 5.7 μmol/L); antituberculosis (MABA assay, avirulent strain Mycobacterium tuberculosis H37Ra, MIC = 5.7 μmol/L; control Rifampicin, MIC = 1.52 nmol/L). Ref: R. A. Davis, et al, JOC, 2004, 69, 4170

1.7 Simple Cyclic Peptides

O

H N H

H

H

36

N H

O

O

HN

O

H N

129

S S

NH

H N

O

H

O

N H

O

NH2

329 Microsclerodermin A Type: Simple cyclic peptides. C47H62N8O16 Powder, [α]D = −133° (c = 0.5, 0.1M NH4HCO3, pH 7.0). Source: Lithistid sponge Microscleroderma sp. (deep water, New Caledonia). Pharm: Antibiotic. Ref: C. A. Bewley, et al, JACS, 1994, 116, 7631 H N

O H N

O

O

OH

O

HN OH

N

NH

O

OH OH

H N

O

N H

O

OH N H

O

OH

O

OH

330 Microsclerodermin B Type: Simple cyclic peptides. C47H62N8O15 Powder, [α]D = −64° (c = 0.2, 0.1M NH4HCO3, pH 7.0). Source: Lithistid sponge Microscleroderma sp. (deep water, New Caledonia). Pharm: Antifungal. Ref: C. A. Bewley, et al, JACS, 1994, 116, 7631 H N

O H N

O

NH

O

HN H

N O H N O

O

O

OH

OH OH

N H

O

O OH

N H

OH OH

130

1 Peptides

331 Microsclerodermin C Type: Simple cyclic peptides. C41H50ClN9O13 Powder, [α]D = −24° (c = 0.063, MeOH/ DMSO 1:1). Source: Lithistid sponges Theonella sp. and Microscleroderma sp. (Philippines). Pharm: Antifungal (Candida albicans). Ref: E. W. Schmidt, et al, Tetrahedron, 1998, 54, 3043 O

Cl

NH2

N

O O

H N O

HN

N

NH

O

O

OH

H N

O

HO HN

OH OH

N H

O

Ph

OH

332 Microsclerodermin D Type: Simple cyclic peptides. C40H49ClN8O12 Powder, [α]D = −56° (c = 0.07, MeOH–DMSO 1:1). Source: Lithistid sponges Theonella sp. and Microscleroderma sp. (Philippines). Pharm: Antifungal (Candida albicans). Ref: E. W. Schmidt, et al, Tetrahedron, 1998, 54, 3043 Cl NH

O O

H N O

NH

N O H N O

HN HO HN

OH

O

O OH

N H

OH OH

333 Microsclerodermin E Type: Simple cyclic peptides. C45H54N8O14 Powder, [α]D = −24° (c = 0.2, MeOH/0.1M NH4HCO3). Source: Lithistid sponges Theonella sp. and Microscleroderma sp. (Philippines). Pharm: Antifungal (Candida albicans). Ref: E. W. Schmidt, et al, Tetrahedron, 1998, 54, 3043│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

1.7 Simple Cyclic Peptides

NH

O COOH

O

H N O

131

NH

HN

N

O

HN

O

OH

O

OH

H N

OH

N H

O

OH O

334 Microsclerodermin F Type: Simple cyclic peptides. C45H56N8O12 Powder, [α]D = −19° (c = 0.62, MeOH aq). Source: Lithistid sponge Microscleroderma sp. (deep water, off Short Dropoff, Koror, Palau). Pharm: Cytotoxic (HCT116, IC50 = 1.1 μmol/L); antifungal (paper disk diffusion assay, yeast Candida albicans, MIC = 1.5 mg/disk). Ref: A. Qureshi, et al, Tetrahedron, 2000, 56, 3679│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev) H HO H HO HO

O

H N O

O

OH

NH OH NH O O

N

N H

HN O

O 2'

N H

3'

N H

335 Microsclerodermin G Type: Simple cyclic peptides. C45H54N8O12 Powder, [α]D = −20° (c = 0.31, MeOH aq). Source: Lithistid sponge Microscleroderma sp. (deep water, off Short Dropoff, Koror, Palau). Pharm: Cytotoxic (HCT116 cell line, IC50 = 1.2 μmol/L); antifungal (paper disk diffusion assay, yeast Candida albicans, MIC = 3 mg/disk). Ref: A. Qureshi, et al, Tetrahedron, 2000, 56, 3679│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

132

1 Peptides

H HO H HO HO

O

H N O

O

NH OH NH

N H

OH

O

HN

O 2'

N

N H

O

3'

O

N H

336 Microsclerodermin H Type: Simple cyclic peptides. C46H58N8O12 Powder, [α]D = −13° (c = 0.95, MeOH aq). Source: Lithistid sponge Microscleroderma sp. (deep water, off Short Dropoff, Koror, Palau). Pharm: Cytotoxic (HCT116, IC50 = 2.0 μmol/L); antifungal (paper disk diffusion assay, yeast Candida albicans, MIC = 12 mg/disk). Ref: A. Qureshi, et al, Tetrahedron, 2000, 56, 3679│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

HO H HO HO

O

H N O

O

NH OH NH O

N H

OH

O N

O

HN

O 2'

N H

3'

N H

337 Microsclerodermin I Type: Simple cyclic peptides. C46H56N8O12 Powder, [α]D = −35° (c = 0.08, MeOH aq). Source: Lithistid sponge Microscleroderma sp. (deep water, off Short Dropoff, Koror, Palau). Pharm: Cytotoxic (HCT116, IC50 = 2.6 μmol/L); antifungal (yeast Candida albicans, paper disk diffusion assay, MIC = 25 mg/disk). Ref: A. Qureshi, et al, Tetrahedron, 2000, 56, 3679│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

1.7 Simple Cyclic Peptides

133

HO H HO HO

O

H N O

O

N H

OH

NH OH

O

HN 2'

N

NH

O

N H

O

3'

O

N H

338 Microsporin A Type: Simple cyclic peptides. C28H40N4O5 Oil, [α]D = +11.6° (c = 0.17, CH2Cl2). Source: Marine-derived fungus Microsporum cf. gypseum from bryozoan Bugula sp. (Virgin Is., USA). Pharm: Histone deacetylase inhibitor (marked); cytotoxic (HCT116, NCIs 60-cancer-cell panel). Ref: W. Gu, et al, Tetrahedron, 2007, 63, 6535 O

H

N

O O

N H O

NH

N H

O

339 Microsporin B Type: Simple cyclic peptides. C28H42N4O5 Oil, [α]D = −39.8° (c = 0.44, CH2Cl2). Source: Marine-derived fungus Microsporum cf. gypseum from bryozoan Bugula sp. (Virgin Is., USA). Pharm: Histone deacetylase inhibitor (marked); cytotoxic (HCT116, NCIs 60-cancer-cell panel). Ref: W. Gu, et al, Tetrahedron, 2007, 63, 6535 OH H N

O N H O N H

O NH O

134

1 Peptides

340 Mixirin A Type: Simple cyclic peptides. C48H74N12O14 Amorph. powder, mp 285–286 °C, [α]D22 = −18.2° (c = 0.16, MeOH). Source: Marine-derived bacterium Bacillus sp. MIX62 (psychrophilic, cold water, culture, sea mud near North Pole). Pharm: Cytotoxic (HCT116, IC50 = 0.68 μg/mL); antibiotic. Ref: H. L. Zhang, et al, CPB, 2004, 52, 1029│ M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) O H 2N

O

O

O

O

O

HO

N H

N

O

O

H N

H 2N

H N

N H

NH

NH2

O

OH

O

NH2 NH N H

O

H

O

341 Mixirin B Type: Simple cyclic peptides. C45H68N12O14 Source: Marine-derived bacterium Bacillus sp. MIX-62 (psychrophilic, cold water, culture, sea mud near North Pole). Pharm: Cytotoxic (HCT116, IC50 = 1.6 μg/mL); antibiotic. Ref: H. L. Zhang, et al, CPB, 2004, 52, 1029│ M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) O H 2N

O H 2N HO

O

O

NH H N

H N

N H

O

O O

O N H

NH2

O

OH

NH2 NH

O

N H

N

O H

O

342 Mixirin C Type: Simple cyclic peptides. C47H72N12O14 Source: Marine-derived bacterium Bacillus sp. MIX-62 (psychrophilic, cold water, culture, sea mud near North Pole). Pharm: Cytotoxic (HCT116, IC50 = 1.3 μg/mL); antibiotic. Ref: H. L. Zhang, et al, CPB, 2004, 52, 1029│ M. D. Lebar, et al, NPR, 2007, 24, 774 (rev)

1.7 Simple Cyclic Peptides

O H 2N

O

O

NH H N

H 2N HO

H N

N H

O

O O

N

O H NH2 NH

O N H

NH2

O

OH

O

135

O

N H

O

343 Motuporin Nodularin 5 Type: Simple cyclic peptides. C40H57N5O10 Glass, [α]D = −83.8°. Source: Lithistid sponge Theonella swinhoei (Papua New Guinea). Pharm: Cytotoxic (in vitro: P388, IC50 = 6 μg/mL, A549, IC50 = 2.4 μg/mL, HEY, IC50 = 2.8 μg/mL, LoVo, IC50 = 2.3 μg/mL, MCF7, IC50 = 12.4 μg/mL, U373MG, IC50 = 2.4 μg/mL); protein phosphatase 1 inhibitor. Ref: E. D. de Silva, et al, Tet. Lett., 1992, 33, 1561│ R. J. Valentekovich, et al, JACS, 1995, 117, 9069│R. Samy, et al, JOC, 1999, 64, 2711│T. Hu, et al, JOC, 1999, 64, 3000│S. M. Bauer, et al, JACS, 1999, 121, 6355 HOOC O

NH

O N

O

HN

O N H

O

HN

O COOH

344 Mutremdamide A Type: Simple cyclic peptides. C44H65N11O18S Amorph. powder, [α]D23 = −33° (c = 0.1, MeOH). Source: Lithistid sponges Theonella swinhoei ssp. swinhoei, Theonella swinhoei ssp. verrucosa and Theonella cupola (deep water, depth of 90–120 m, Mutremdiu Reef, Palau). Pharm: Anti-inflammatory (in vivo mouse paw edema model, reduced carrageenan-induced paw edema in a dose-dependent manner in both early (0–6 h) and late (24–96 h) phases, 0.3 mg/kg, 60% reduction of edema, compare with current NSAIDs naproxen (ED50 = 40 mg/kg), Mutremdamide A is nearly 100 times more potent); anti-inflammatory (hmn antipsoriatic effects, PHK, dose-dependent response, inhibits release of both TNFa and IL-8). Ref: A. Plaza, et al, JOC, 2010, 75, 4344│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

136

1 Peptides

O

H 2N

N H

NH

O

H

O

O

O

N H

15

OH

11z

N

21

2'

O

NH OH

N

O

H O

O O O

HN

H N

29

O

H

30

O

S O

NH 2

N H O OH

345 Nodularin Nodularin 1 Type: Simple cyclic peptides. C41H60N8O10 Source: Cyanobacterium Nodularia spumigena (from marine brackish wate). Pharm: Phycotoxin; hepatotoxin; tumour promoter; protein phosphatase inhibitor. Ref: K. L. Rinehart, et al, JACS, 1988, 110, 8557 O

OH

O

N

N H

O NH O

NH H 2N

O O

H N

NH O

N H

O

OH

346 Orbiculamide A Type: Simple cyclic peptides. C46H62BrN9O10 Powder, [α]D23 = −60° (c = 0.005, MeOH). Source: Lithistid sponge Theonella sp. Pharm: Cytotoxic (P388, IC50 = 4.7 μg/mL). Ref: N. Fusetani, et al, JACS, 1991, 113, 7811 O HN N H

O O

N H

O

HN O

NH

O O

N O

HO

HN

O

N H Br N H

1.7 Simple Cyclic Peptides

137

347 Pahayokolide A Type: Simple cyclic peptides. C72H105N13O20 Amorph. powder, [α]D25 = −18° (c = 0.001, MeOH). Source: Cyanobacteria Lyngbya sp. nov (fresh water) and Lyngbya sp. Pharm: Cytotoxic (H460, IC50 = 2.13 μmol/L; A498, IC50 = 2.61 μmol/L; SK-OV-3, IC50 = 2.76 μmol/L; CEM, IC50 = 3.27 μmol/L; SK-MEL-28, IC50 = 5.74 μmol/L; U251, IC50 = 13.33 μmol/L; SKBR3, IC50 = 16.70 μmol/L; HT29 Colon adenocarcinoma GR-III, IC50 = 44.57 μmol/L); antibacterial (Bacillus megaterium, IZD = 32 mm, MIC = 5 μg/mL; Bacillus subtilis, IZD = 32 mm, MIC = 5 μg/mL); anticyanobacterial (Nostoc Ev-1, IZD = 30 mm); antifungal (yeast Saccharomyces cerevisiae, IZD = 20 mm); algicide (green algae: Chlamydomonas sp. Ev-29, IZD = 20 mm, MIC = 10 μg/mL; Ulothrix sp. Ev-17, IZD = 22 mm; Chlorella sp. 2-4, IZD = 20 mm); toxic (brine shrimp Artemia salina, 0.01 mg/mL, mortality = 6.9%, 0.1 mg/mL, mortality = 7.5%, 1 mg/mL, mortality = 55%). Ref: J. Berry, et al, Comp. Biochem. Physiol, C, 2004, 139, 231│T. An, et al, JNP, 2007, 70, 730 HO

N

O O

OH

N O

O

H N

N H

O

HN O

HO

O

H N

N H

O O

H N

H N

O

HN

O

HN

O N

O

56

O

OH

O

NH2

HO

348 Palauamide Type: Simple cyclic peptides. C46H69N5O10 Oil, [α]D23 = −22° (c = 0.4, MeOH). Source: Cyanobacterium Lyngbya sp. (Palau, Oceania). Pharm: Cytotoxic (KB, IC50 = 13 nmol/L). Ref: F. D. Horgen, et al, JNP, 2002, 65, 487│P. G. Williams, et al, JNP, 2003, 66, 1545│H. Sugiyama, et al, Tet. Lett., 2009, 50, 7343

138

1 Peptides

H N N O

O O O

O

O

37

N O H NH N

OH

O

O

349 Pedein A Type: Simple cyclic peptides. C43H53ClN8O13 Powder, [α]D20 = −46.5° (c = 0.37, DMSO/MeOH). Source: Marine myxobacterium Chondromyces pediculatus. Pharm: Antifungal (Rhodotorula glutinis, Saccharomyces cerevisiae and Candida albicans, MIC = 0.6–1.6 μg/mL). Ref: B. Kunze, et al, J. Antibiot. (Tokyo) 2008, 61, 18 OH

O

O H

HN

HO O

N H

HO

H NH

OH

O

O

N OH O

NH

H N

NH O

O Cl

N H

350 Pedein B Type: Simple cyclic peptides. C43H54N8O13 Amorph. solid. Source: Marine myxobacterium Chondromyces pediculatus. Pharm: Antifungal (Rhodotorula glutinis, Saccharomyces cerevisiae and Candida albicans, MIC = 0.6–1.6 μg/mL). Ref: B. Kunze, et al, J. Antibiot. (Tokyo) 2008, 61, 18

1.7 Simple Cyclic Peptides

139

OH

O

O H

HN

HO O

N H

HO

H NH

OH

O

O

N OH O

NH

NH

H N

O

O N H

351 Perthamide B Type: Simple cyclic peptides. C43H63BrN10O14 Amorphous solid, mp 228–231 °C, [α]D23 = +19.8° (c = 0.2, Py). Source: Lithistid sponge Theonella sp. (Australia). Pharm: IL-1β binding inhibitor (intact EL4.6.1 cells, IC50 = 27.6 μg/mL). Ref: N. K. Gulavita, et al, Tet. Lett., 1994, 35, 6815 O OH

H 2N HN O N

O H N

O

N O

O

Br

O

NH

OH

O O

H N

O

HN

N O

NH2

OH

352 Perthamide C Type: Simple cyclic peptides. C44H65N11O18S Amorph. solid, [α]D25 = −6.3° (c = 2.8, CHCl3). Source: Lithistid sponge Theonella swinhoei (Vangunu I., Solomon Is.). Pharm: Anti-inflammatory (mouse oedema model, lacking cytotoxicity). Ref: C. Festa, et al, Tetrahedron, 2009, 65, 10424│V. Sepe, et al, Tetrahedron, 2010, 66, 7520 (Structure revised)

140

1 Peptides

O

H 2N

N H

NH

O

O

O

N H

15

OH

O

11

N

21

2'

O

NH OH

N

O

H O

O O O

HN

H N

29

O

H

30

O

S O

N H O

NH2

OH

353 Perthamide D Type: Simple cyclic peptides. C44H65N11O17S Amorph. powder, [α]D25 = −4.1° (c = 0.1, CHCl3). Source: Lithistid sponge Theonella swinhoei (barrier reef of Vangunu I., Solomon Is.). Pharm: Anti-inflammatory (in vivo, mouse paw edema model, 0.3 mg/kg, 46% reduction of edema); anti-inflammatory (hmn antipsoriatic effects, PHK, too cytotoxic at 10 μmol/L). Ref: C. Festa, et al, Tetrahedron, 2009, 65, 10424│V. Sepe, et al, Tetrahedron, 2010, 66, 7520 (structure revised)│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

O

H 2N

NH

O

O

O N H

N H

15

OH

O

11

N

21

2'

O

NH O

N

H O

O O O

HN

H N

29

O

H

30

O

S O

N H O

NH2

OH

354 Perthamide E Type: Simple cyclic peptides. C45H67N11O18S Source: Lithistid sponge Theonella swinhoei (reef at depth of 22 m, western coast of Malaita I., Solomon Is.). Pharm: Anti-inflammatory (hmn antipsoriatic effects, PHK, dose-dependent response, significantly inhibits release of IL-8). Ref: C. Festa, et al, Tetrahedron, 2011, 67, 7780│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

1.7 Simple Cyclic Peptides

O

H2 N

O

O N H

NH

O

141

N H

15

OH

O

11

N

21

2'

O

NH OH

N

O

H O

O O O

HN

H N

29

O

H

30

O

S O

N H O

NH2

OH

355 Perthamide F Type: Simple cyclic peptides. C45H67N11O17S Source: Lithistid sponge Theonella swinhoei (reef at depth of 22 m, western coast of Malaita I., Solomon Is.). Pharm: Antiinflammatory (hmn antipsoriatic effects, PHK, too cytotoxic at 10 μmol/L). Ref: C. Festa, et al, Tetrahedron, 2011, 67, 7780│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev)

O

H 2N

N H

NH

O

O

O

N H

15

OH

O

11

N

21

2'

O

NH N

O

H O

O O O

HN

H N

29

O

H

30

O

S O

N H O

NH2

OH

356 Perthamide G Type: Simple cyclic peptides. C43H63N11O18S Source: Lithistid sponge Theonella swinhoei (Solomon Is.). Pharm: Anti-inflammatory. Ref: C. Festa, et al, Tetrahedron, 2012, 68, 2851 H 2N

O

O

NH

O

O N H

NH OH

O

OH

O N O

O

N H

N O O

HN H N O

O

O

N H S O O OH

NH2

142

1 Peptides

357 Perthamide H Type: Simple cyclic peptides. C44H65N11O15 Source: Lithistid sponge Theonella swinhoei (Solomon Is.). Pharm: Anti-inflammatory. Ref: C. Festa, et al, Tetrahedron, 2012, 68, 2851

H 2N

O

O N H

NH

O

O

NH OH

OH

N O O

HN

O

O

O

N H

H N

N O

NH2

N H

OH

O

O

358 Perthamide I Type: Simple cyclic peptides. C45H67N11O15 Source: Lithistid sponge Theonella swinhoei (Solomon Is.). Pharm: Anti-inflammatory. Ref: C. Festa, et al, Tetrahedron, 2012, 68, 2851

H 2N

O

NH

O

O

O N H

NH OH

O

OH

O N O

O

N H

N O O

HN H N O

OH

O N H

NH2

359 Perthamide J Type: Simple cyclic peptides. C44H62N10O15 Source: Lithistid sponge Theonella swinhoei (Solomon Is.). Pharm: Anti-inflammatory. Ref: C. Festa, et al, Tetrahedron, 2012, 68, 2851

1.7 Simple Cyclic Peptides

H 2N

O

O

O N H

NH

O

OH

NH OH

143

N O O

HN

O

O

O

N H

H N

N

NH O

O

O O

360 Phakellistatin 1 Type: Simple cyclic peptides. C45H61N7O8 Amorphous solid, mp 247–249 °C, [α]D25 = −50.5° (c = 0.33, CHCl3); mp 240–242 °C. Source: Sponges Phakellia costata (Truk, Federated States of Micronesia), Stylotella aurantium (Palau, Oceania) and Hymeniacidon sp. (Okinawa). Pharm: Cytotoxic (P388, ED50 = 7.5 μg/mL); cytotoxic (J774.A1, IC50 = 2.6 × 10−3 mol/L, WEHI-164, IC50 = 9.98 × 10−4 mol/L, HEK-293, IC50 = 3.9 × 10−3 mol/L). Ref: G. R. Pettit, et al, JNP, 1993, 56, 260│A. Napolitano, et al, Tetrahedron, 2003, 59, 10203

O N H N H

OH

N

O N

O O

O HN O H N

N

O

361 Phakellistatin 2 Type: Simple cyclic peptides. C45H61N7O8 Amorphous solid, mp 199–201 °C, [α]D23 = −148° (c = 0.34, MeOH). Source: Sponge Phakellia carteri (Comoros Is.). Pharm: Cytotoxic (P388, natural sample, ED50 = 0.34 μg/mL, synthetic sample, ED50 = 24 μg/mL). Ref: G. R. Pettit, et al, Bioorg. Med. Chem. lett., 1993, 3, 2869│G. R. Pettit, et al, JNP, 1999, 62, 409

144

1 Peptides

H N

N HO

O O

NH O

O O HN

H N

N

N O

O

362 Phakellistatin 3 Type: Simple cyclic peptides. C42H54N8O9 Amorphous powder, mp 178–180 °C, [α]D24 = −147° (c = 0.22, CH3OH). Source: Sponge Phakellia carteri (Comoros Is.). Pharm: Cytotoxic (P388, ED50 = 0.33 μg/mL). Ref: G. R. Pettit, et al, JOC, 1994, 59, 1593

O

NH

O

N

N H

O O O

O

H N

N N

NH

OH

H O

H NH

HO

363 Phakellistatin 4 Type: Simple cyclic peptides. C41H55N7O9 Amorphous powder, [α]D = −97° (c = 2, MeOH). Source: Sponge Phakellia costata (Truk, Federated States of Micronesia). Pharm: Cytotoxic. Ref: G. R. Pettit, et al, Heterocycles, 1995, 40, 501│G. R. Pettit, et al, Bioorg. Med. Chem. Lett., 1995, 5, 1339 OH

O

N HN O

N

N H O

O

O

NH

OH O O N H

NH

1.7 Simple Cyclic Peptides

145

364 Phakellistatin 5 Type: Simple cyclic peptides. C35H52N8O8S Powder, [α]D = −102° (c = 2, MeOH). Source: Sponge Phakellia costata (Truk, Federated States of Micronesia). Pharm: Cytotoxic. Ref: G. R. Pettit, et al, Bioorg. Med. Chem. Lett., 1994, 4, 2091 S

O

O

NH NH O

N H

H N

O HN O

N

O O

N H

H 2N O

365 Phakellistatin 6 Type: Simple cyclic peptides. C47H62N8O7 Powder, [α]D = −129° (c = 0.4, MeOH). Source: Sponge Phakellia costata (Truk, Federated States of Micronesia). Pharm: Cytotoxic (P388, ED50 = 0.185 μg/mL; OVCAR-3; GI50 = 0.025 μg/mL; SF295; GI50 = 0.041 μg/mL; A498, GI50 = 0.078 μg/mL; NCI-H460, GI50 = 0.019 μg/mL; KM20L2, GI50 = 0.021 μg/mL; SK-MEL-S, GI50 = 0.032 μg/mL). Ref: G. R. Pettit, et al, Bioorg. Med. Chem. Lett., 1994, 4, 2677

O

HN

N H

N N H O

O O

N

O HN

O H N

N

O

366 Phakellistatin 7 Type: Simple cyclic peptides. C59H84N10O11 Amorphous powder, mp 192–195 °C, [α]D = −106° (c = 0.2, MeOH). Source: Sponge Phakellia costata (Truk, Federated States of Micronesia). Pharm: Cytotoxic (P388, ED50 = 3.0 μg/mL). Ref: G. R. Pettit, et al, Heterocycles, 1995, 40, 501│G. R. Pettit, et al, Bioorg. Med. Chem. Lett., 1995, 5, 1339

146

1 Peptides

O

NH

HN O N

O

H N

N H

O

O

O

O

N

O N

HN

H N

N

O

O

OH

367 Phakellistatin 8 Type: Simple cyclic peptides. C61H88N10O11 Crystals (MeOH aq), mp 188–191 °C, [α]D = −112° (c = 0.2, MeOH). Source: Sponge Phakellia costata (Truk, Federated States of Micronesia). Pharm: Cytotoxic (P388, ED50 = 2.9 μg/mL). Ref: G. R. Pettit, et al, Heterocycles, 1995, 40, 501│G. R. Pettit, et al, Bioorg. Med. Chem. Lett., 1995, 5, 1339

O

NH

HN O N

O N

H N

N H

O

O O

O H N

N

O O N

HN

O

OH

368 Phakellistatin 9 Type: Simple cyclic peptides. C60H86N10O11 Amorphous powder, mp 184–188 °C, [α]D = −113° (c = 0.7, MeOH). Source: Sponge Phakellia costata (Truk, Federated States of Micronesia). Pharm: Cytotoxic (P388, ED50 = 4.1 μg/mL). Ref: G. R. Pettit, et al, Heterocycles, 1995, 40, 501│G. R. Pettit, et al, Bioorg. Med. Chem. Lett., 1995, 5, 1339

1.7 Simple Cyclic Peptides

O

O

O

O O

N

H N

N H

NH

HN

O

O

N

N

O O N

HN

H N

147

O

OH

369 Phakellistatin 10 Hymenamide H Type: Simple cyclic peptides. C47H69N9O9 Amorphous powder, mp 217–219 °C, [α]D25 = −128° (c = 0.19, MeOH); [α]D20 = −88° (c = 1.02, MeOH). Source: Sponge Phakellia costata (Truk, Federated States of Micronesia). Pharm: Cytotoxic (P388, ED50 = 2.1 μg/mL, cell growth inhibitor). Ref: M. Tsuda, et al, Tetrahedron, 1994, 50, 4667│G. R. Pettit, et al, Heterocycles, 1995, 40, 501│G. R. Pettit, et al, Bioorg. Med. Chem. Lett., 1995, 5, 1339│G. R. Pettit, et al, JNP, 1995, 58, 961

O N H

N O NH O

HO O

N O O

H N O H N O

N

N H

N H

370 Phakellistatin 11 Type: Simple cyclic peptides. C53H67N9O9 Amorphous powder, mp 194–196 °C, [α]D25 = −163° (c = 0.08, MeOH). Source: Sponge Phakellia costata (Truk, Federated States of Micronesia). Pharm: Cytotoxic (P388, ED50 = 0.20 μg/mL, cell growth inhibitor). Ref: G. R. Pettit, et al, Heterocycles, 1995, 40, 501│G. R. Pettit, et al, Bioorg. Med. Chem. Lett., 1995, 5, 1339│G. R. Pettit, et al, JNP, 1995, 58, 961; 2001, 64, 883

148

1 Peptides

O

H N

N

H 2N

O NH O

O

O Ph

Ph

O

N

O HN

N HN

Ph O

N H

O

371 Phakellistatin 19 Type: Simple cyclic peptides. C51H69N9O9 Source: Sponge Phakellia sp. Pharm: Cytotoxic (NSCLC (Lung) A549, GI50 = 4.41 × 10-7 mol/L, TGI = 1.16 × 10-6 mol/L, LC50 > 1.05 × 10-5 mol/L; HT29, GI50 = 4.62 × 10-7 mol/L, TGI = 6.72 × 10-7 mol/L, LC50 > 1.05 × 10-5 mol/L; MDA-MB-231, GI50 = 5.15 × 10-7 mol/L, TGI = 1.47 × 10-6 mol/L, LC50 > 1.05 × 10-5 mol/L). Ref: P. -G. Marta, et al, JMC, 2013, 56, 9780

N

H N

O

HN

O O

O N HO

NH H N O

O

N

O

H N

N H

O

372 Pseudoalterobactin A Type: Simple cyclic peptides. C41H63N11O21S Source: Marine-derived bacterium Pseudoalteromonas sp. KP20-4. Pharm: Siderophore. Ref: K. Kanoh, et al, J. Antibiot., 2003, 56, 871 H N O

N H

H N H 2N O H N O

OH OH HO

O O O

NH2

O S OH O

H N H N

OH H N

HO O

O

H2N

N H

O HO

O OH O

1.7 Simple Cyclic Peptides

149

373 Pseudoalterobactin B Type: Simple cyclic peptides. C41H63N13O21S Source: Marine-derived bacterium Pseudoalteromonas sp. KP20-4. Pharm: Siderophore. Ref: K. Kanoh, et al, J. Antibiot., 2003, 56, 871 H N O

H N

OH H N

HO O N H

H N H 2N

O

O O HN H2N

NH2

O

H N

O HO

N H

O OH O

N H

OH H N

OH

HO

O S

OH

374 Pullularin A Type: Simple cyclic peptides. C42H57N5O9 Source: Mangrove-derived fungus Bionectria ochroleuca from mangrove Sonneratia caseolaris (leaf, Hainan, China), terrestrial fungus. Pharm: Cytotoxic (L5178Y, 10 μg/mL, Survival Rate = 1.7%, EC50 = 2.60 μg/mL, control Kahalalide F, EC50 = 6.40 μg/mL). Ref: M. Isaka, et al, Tetrahedron, 2007, 63, 6855│W. Ebrahim, et al, Mar. Drugs, 2012, 10, 1081 O

N

HN O N

OH

O N H

O O

O

O

O N

375 Pullularin C Type: Simple cyclic peptides. C41H55N5O9 Source: Mangrove-derived fungus Bionectria ochroleuca from mangrove Sonneratia caseolaris (leaf, Hainan, China), terrestrial fungus. Pharm: Cytotoxic (L5178Y cell line, 10 μg/mL, Survival Rate = 21.7%, EC50 = 6.70 μg/mL, control Kahalalide F, EC50 = 6.40 μg/mL). Ref: M. Isaka, et al, Tetrahedron, 2007, 63, 6855│W. Ebrahim, et al, Mar. Drugs, 2012, 10, 1081

150

1 Peptides

O

N

HN O O

N

OH

O O

O

O

O N

N H

376 Pullularin F Type: Simple cyclic peptides. C38H52N4O9 Source: Mangrove-derived fungus Bionectria ochroleuca from mangrove Sonneratia caseolaris (leaf, Hainan, China). Pharm: Cytotoxic (L5178Y, 10 μg/mL, Survival Rate = 114.3%, EC50 > 10 μg/mL, control Kahalalide F, EC50 = 6.40 μg/mL). Ref: W. Ebrahim, et al, Mar. Drugs, 2012, 10, 1081 O

OH

HN O N

OH

O

O O

N H

OH O N

377 (cis)-Rolloamide A Type: Simple cyclic peptides. C41H61N7O7 Glass. Source: Sponge Eurypon laughlini (major conformer, Rollo Head, Dominica). Pharm: Cytotoxic (prostate: LNCaP, IC50 = 0.8 μmol/L, PC3MM2, IC50 = 4.7 μmol/L, PC3, IC50 = 1.4 μmol/L, DU145, IC50 = 0.85 μmol/L, breast: MDA468, IC50 = 0.38 μmol/L, MDA435, IC50 = 0.40 μmol/L, BT549, IC50 = 1.3 μmol/L, MDA361, IC50 = 5.8 μmol/L, MCF7, IC50 = 0.88 μmol/L, MDA231, IC50 = 2.2 μmol/L, ovarian: OVCAR-3, IC50 = 0.17 μmol/L,SK-OV-3, IC50 = 1.6 μmol/L, glioma: U-87-MG, IC50 = 0.72 μmol/L, renal: A498, IC50 = 1.8 μmol/L). Ref: D. E. Williams, et al, JNP, 2009, 72, 1253

1.7 Simple Cyclic Peptides

O

H N

N H

N

151

O cis

O N

O

O N H

O NH

N O

378 (trans)-Rolloamide A Type: Simple cyclic peptides. C41H61N7O7 Glass. Source: Sponge Eurypon laughlini (minor conformer, Rollo Head, Dominica). Pharm: Cytotoxic (prostate: LNCaP, IC50 = 0.8 μmol/L, PC3MM2, IC50 = 4.7 μmol/L, PC3, IC50 = 1.4 μmol/L, DU145, IC50 = 0.85 μmol/L, breast: MDA468, IC50 = 0.38 μmol/L, MDA435, IC50 = 0.40 μmol/ L, BT549, IC50 = 1.3 μmol/L, MDA361, IC50 = 5.8 μmol/L, MCF7, IC50 = 0.88 μmol/L, MDA231, IC50 = 2.2 μmol/L, ovarian: OVCAR-3, IC50 = 0.17 μmol/L, SK-OV-3, IC50 = 1.6 μmol/L, glioma: U-87-MG, IC50 = 0.72 μmol/L, renal: A498, IC50 = 1.8 μmol/L). Ref: D. E. Williams, et al, JNP, 2009, 72, 1253

O

H N

N H

N O

O

O

trans N

O N H

O NH

N O

379 Sclerotide A Type: Simple cyclic peptides. C37H39N7O8 Amorph. yellow powder, [α]D25 = −73° (c = 0.3, MeOH), photointerconvertible to Sclerotide B by radical mechanism. Source: Marine-derived fungus Aspergillus sclerotiorum PT06-1 (Putian Sea Salt Field, Fujian, China). Pharm: Antifungal (Candida albicans, moderate). Ref: J. Zheng, et al, Org. Lett., 2009, 11, 5262

152

1 Peptides

H N HN

OO NH

O

NH O

HO O

N H

HO H

NH

N H

O

380 Sclerotide B Type: Simple cyclic peptides. C37H39N7O8 Amorph. yellow powder, [α]D25 = −73° (c = 0.3, MeOH), photointerconvertible to Sclerotide A by radical mechanism. Source: Marine-derived fungus Aspergillus sclerotiorum PT06-1 (Putian Sea Salt Field, Fujian, China). Pharm: Antifungal (yeast Candida albicans, moderate); cytotoxic (HL60, weak); antibacterial (Pseudomonas aeruginosa). Ref: J. Zheng, et al, Org. Lett., 2009, 11, 5262 H N HN H O

OO NH

NH O

HO O

HO H

N H

NH

N H

O

381 Scytalidamide A Type: Simple cyclic peptides. C50H67N7O7 Fine cryst., mp 147–150 °C, [α]D25 = −151.2° (c = 0.6, MeOH). Source: Marine-derived fungus Scytalidium sp. Pharm: Cytotoxic (HCT116, IC50 = 2.7 μmol/L). Ref: L. T. Tan, et al, JOC, 2003, 68, 8767

N

HN O HN

O N

O O

H N O O O N

NH

1.7 Simple Cyclic Peptides

153

382 Scytalidamide B Type: Simple cyclic peptides. C51H69N7O7 Fine cryst., mp 141–143 °C, [α]D25 = −156.9° (c = 0.6, MeOH). Source: Marine-derived fungus Scytalidium sp. Pharm: Cytotoxic (HCT116, IC50 = 11.0 μmol/L). Ref: L. T. Tan, et al, JOC, 2003, 68, 8767

N

HN O HN

O

O O

H N O O O

NH

N

N

383 Solonamide A Type: Simple cyclic peptides. C31H48N4O5 Source: An unidentified marine-derived bacterium (closely related to Photobacterium alotolerans) from an unidentified mussel (tropical Pacific Ocean). Pharm: agr Quorum sensing system inhibitor. Ref: M. Mansson, et al, Mar. Drugs, 2011, 9, 2537

O

NH NH O HN O

O

O

N H

2

384 Solonamide B Type: Simple cyclic peptides. C33H52N4O5 Source: An unidentified marine-derived bacterium (closely related to Photobacterium alotolerans) from an unidentified mussel (tropical Pacific Ocean). Pharm: agr Quorum sensing system inhibitor. Ref: M. Mansson, et al, Mar. Drugs, 2011, 9, 2537

O

NH NH O HN O

O 4

N H

O

154

1 Peptides

385 Stylissamide X Type: Simple cyclic peptides. C51H69N9O9 Source: Sponge Stylissa sp. (Biak, Indonesia). Pharm: Cytotoxic (inhibits HeLa cell migration at sub-inhibitory concentrations). Ref: M. Arai, et al, Bioorg. Med. Chem. Lett., 2012, 22, 1818

OH H N

HN O N

O

N

O

O O

O

N H

NH

O O N

N H NH

386 Stylissatin A Type: Simple cyclic peptides. C49H63N7O8 Source: Sponge Stylissa massa (Loloata I., Papua New Guinea). Pharm: NO production inhibitor (LPS-stimulated macrophages). Ref: M. Kita, et al, Tet. Lett., 2013, 54, 6826

H N

HN HN

O

O O O

O

OH

O

NH

O N

N N H

387 Stylopeptide 1 Type: Simple cyclic peptides. C40H61N7O8 Crystals (MeOH aq), mp 228–229 °C, [α]D25 = −128° (c = 0.2, MeOH). Source: Sponges Stylotella aurantium, Stylotella sp. (Papua New Guinea) and Phakellia costata (Truk, Federated States of Micronesia). Pharm: Cytotoxic (P388). Ref: G. R. Pettit, et al, JOC, 1995, 60, 8257; 1996, 61, 2322

1.7 Simple Cyclic Peptides

155

O N H O

N HN O

N O O OH O O

NH

NH

N H

388 Stylostatin 1 Type: Simple cyclic peptides. C36H54N8O9 Colorless crystalline solid, mp 210 °C, [α]D25 = −116° (c = 0.29, CH3OH). Source: Sponge Stylotella sp. (Papua New Guinea). Pharm: Cytotoxic (P388, ED50 = 0.8 μg/mL). Ref: G. R. Pettit, et al, JOC, 1992, 57, 7217; 1993, 58, 3222 O NH2

O

O

NH N

H N

N H

O

OH

O

NH

O O N H

H N O

389 Theonegramide Type: Simple cyclic peptides. C70H101BrN16O26 White powder, [α]D = +19° (c = 0.4, NeCN). Source: Lithistid sponge Theonella swinhoei (Philippines). Pharm: Antifungal. Ref: C. A. Bewley, et al, JOC, 1994, 59, 4849 (erratum: 1995, 60, 2644) Br

N

HO HN

HN O H 2N

O

HN O – O HO O HO O OH N O N NH

OH O

O

H 2N O

N H

O HN O

+

O

H N

OH

O

N H HO

OH NH

O H N

NH O HO

156

1 Peptides

390 Theonellamide A Type: Simple cyclic peptides. C76H99BrN16O281+ Powder, [α]D23 = +23° (c = 0.1, n–PrOH/H2O 2:1). Source: Lithistid sponge Theonella sp. (Japan waters). Pharm: Cytotoxic (P388, IC50 = 5.0 μg/mL). Ref: S. Matsunaga, et al, JOC, 1995, 60, 1177 HO

O

N H OH

O

NH

OH O HN O

Br

OH HN

O

H 2N

NH OH O

H N

OH

O

H 2N

HN

OH

+

OH

HO

O

N H N

O

OH

O

O

O

H N

N H

NH O

HO

NH

O

N

HO

O

391 Theonellamide B Type: Simple cyclic peptides. C70H89BrN16O23 Powder, [α]D23 = +6.6° (c = 0.1, n–PrOH/H2O 2:1). Source: Lithistid sponge Theonella sp. (Japan waters). Pharm: Cytotoxic (P388, IC50 = 1.7 μg/mL). Ref: S. Matsunaga, et al, JOC, 1995, 60, 1177 O HO

O

N H NH HO

O

O HN O

Br H 2N

OH

O

OH HN

N H

O HN

O

O

N NH

OH O

N H HO

NH

O

O H N O

H 2N

OH

N

H N

NH O

HO

O

392 Theonellamide C Type: Simple cyclic peptides. C69H87BrN16O22 [α]D23 = +0.01° (c = 0.1, n–PrOH/ H2O 2:1). Source: Lithistid sponge Theonella sp. (Japan waters). Pharm: Cytotoxic (P388, IC50 = 2.5 μg/mL). Ref: S. Matsunaga, et al, JOC, 1995, 60, 1177

1.7 Simple Cyclic Peptides

157

O O

N H NH HO

O

O HN O

OH

O

OH HN

O

N H

HN

O

O

O

NH

H N

OH O

H N

N H

O

H 2N

NH

O

N

H 2N

OH

N

NH O

HO

HO

O

Br

393 Theonellamide D Type: Simple cyclic peptides. C74H95Br2N16O271+ Powder, [α]D23 = +16° (c = 0.1, n–PrOH/H2O 2:1). Source: Lithistid sponge Theonella sp. (Japan waters). Pharm: Cytotoxic (P388, IC50 = 1.7 μg/mL). Ref: S. Matsunaga, et al, JOC, 1995, 60, 1177 O O

N H NH HO

O

HN O

Br

O

OH O

O N+

O HN O

OH

OH NH

O O

H N O

H 2N

N H

OH N

HO

NH

H 2N

OH HN

O

O

OH

O

N H HO

H N

NH O

HO

O

Br

394 Theonellamide E Type: Simple cyclic peptides. C75H97Br2N16O28 [α]D23 = +20° (c = 0.1, n–PrOH/ H2O 2:1). Source: Lithistid sponge Theonella sp. (Japan waters). Pharm: Cytotoxic (P388, IC50 = 0.9 μg/mL). Ref: S. Matsunaga, et al, JOC, 1995, 60, 1177

158

1 Peptides

O O

N H NH HO OH

O

O HN O

Br

OH HN

O

O NH

OH O

OH

H N

HN

OH

+

O

NH

O

N

O

H N

N H HO

O

H 2N

O

N H N

OH

HO

H 2N

O

OH

O

NH O

HO

O

Br

395 Theonellapeptolide IIIe Type: Simple cyclic peptides. C71H127N13O16 mp 184–186 °C, [α]D22 = −48.6° (c = 1.0, MeOH). Source: Sponge Lamellomorpha strongylata (deep water, New Zealand). Pharm: Cytotoxic (P388, 7.4 μg/mL). Ref: S. Li, et al, JNP, 1998, 61, 724 O N NH

O

O

N H

O

O

O

N O

O

H N O

O

H N

N

N H

O

N

O

HN

O

O N

N

O NH

O

396 Theopalauamide Type: Simple cyclic peptides. C76H99BrN16O27 Powder, [α]D = +19° (c = 0.4, MeOH). Source: Lithistid sponge Theonella swinhoei (filamentous bacterial symbionts, Palau and Mozambique). Pharm: Antifungal (Candida albicans); antifungal (molecular barcoded yeast open reading frame library method (MoBY-ORF) used to identify mode of action of theopalauamide through binding 3-β hydroxysterols, a new class of sterol binding agents). Ref: E. W. Schmidt, et al, JOC, 1998, 63, 1254│ A. E. Wright, Current Opinion in Biotechnology 2010, 21, 801

1.7 Simple Cyclic Peptides

–

O

O

O

Br

N H HO HO

HN H

N H O

H N H

OH

+

O

O

H N

N H

O

O

NH

O

O

H N

O

HN

OH

H N

OH

OH

N

O

H 2N

N

OH

O HN O H

O O

HO

159

NH H

O HO

HO

N H2

397 Trichoderide Type: Simple cyclic peptides. C22H35N5O7 Source: Marine-derived fungus Trichoderma reesei (sea mud, China). Pharm: Cytotoxic (A375-S2 melanoma cell line, moderate). Ref: Y. Sun, et al, Pharmazie, 2006, 61, 809 N

O

O H N

NH

H HN

O

O

O

OH

N H

O

398 Tumescenamide A Type: Simple cyclic peptides. C37H57N5O8 Source: Marine-derived streptomycete Streptomyces tumescens (sediment, Big Drop-off, Palau, Oceania). Pharm: Induces reporter gene expression (under control of insulin-degrading enzyme (IDE) promoter, suggesting promise as a potential treatment for Alzheimer’s disease). Ref: K. Motohashi, et al, J. Antibiot., 2010, 63, 549

H N HO

O O O O H N

HN

O

NH

H N 2

O

O

160

1 Peptides

399 Turnagainolide B Type: Simple cyclic peptides. C30H44N4O6 White powder, [α]D20 = −90° (c = 0.05, CH2Cl2/MeOH 1:1). Source: Marine-derived bacterium Bacillus sp. (sediment, Turnagain, British Columbia, Canada). Pharm: Inositol 5-phosphatase SHIP1 activator. Ref: D. Li, et al, JNP, 2011, 74, 1093

O

HN

3S

O HN

O

O O O

NH

N H

400 Unguisin A Type: Simple cyclic peptides. C40H54N8O7 Amorph. solid. Source: Marine-derived fungus Emericella unguis from both unidentified mollusc and unidentified jellyfish. Pharm: Antibacterial (Staphylococcus aureus, moderate). Ref: J. Malmstrom, JNP, 1999, 62, 787 O

NH

O

H N

N H

O NH

O NH

O

H N

O

N H

N H

O

401 Unguisin B Type: Simple cyclic peptides. C37H56N8O7 Amorph. solid. Source: Marine-derived fungus Emericella unguis from both unidentified mollusc and unidentified jellyfish. Pharm: Antibacterial (Staphylococcus aureus, moderate). Ref: J. Malmstrom, JNP, 1999, 62, 787 O

NH

O

H N

N H

O NH

O NH O

O

H N O

N H

N H

1.8 Cyclic Peptides with Oxazole

161

402 Wainunuamide Type: Simple cyclic peptides. C38H51N9O7 Oil, [α]D25 = −64.1° (c = 0.01, MeOH). Source: Sponge Stylotella aurantium (Fiji). Pharm: Cytotoxic (weak). Ref: J. Tabudravu, et al, Tet. Lett., 2001, 42, 9273 O N

N N

H N

O

N H

HN

O

O

O

O

N

NH

H N O

1.8 Cyclic Peptides with Oxazole 403 Discobahamin A Type: Cyclic peptides with oxazole. C47H65N9O11 Pale yellow gum, [α]D24 = −29° (c = 0.5, MeOH). Source: Lithistid sponge Discodermia sp. (Bahamas). Pharm: Antifungal. Ref: S. P. Gunasekera, et al, JNP, 1994, 57, 79

O

OH

N H

O

H N O

N

N H O

O

OH

NH

O

N H

NH H N

O

N O

O

404 Discobahamin B Type: Cyclic peptides with oxazole. C48H67N9O11 Pale yellow gum, [α]D24 = −31° (c = 0.1, MeOH). Source: Lithistid sponge Discodermia sp. (Bahamas). Pharm: Antifungal. Ref: S. P. Gunasekera, et al, JNP, 1994, 57, 79

162

1 Peptides

O N H

OH

O

H N O

N

N H O

O

OH

NH

N H

O NH H N

O

N O

O

405 Keramamide E Type: Cyclic peptides with oxazole. C53H75BrN10O12 Solid, [α]D22 = −39° (c = 0.1, MeOH). Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 1.60 μg/mL, KB, IC50 = 1.55 μg/mL). Ref: J. Kobayashi, et al, Tetrahedron, 1995, 51, 2525 OH O

O

HN

N H

H N

H N

N O

O

O

H N

O

N

O

O

O

H N

N H

O

HO Br N H

406 Keramamide M Type: Cyclic peptides with oxazole. C52H73BrN10O15S Amorph. solid. Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 2.4 μg/mL, KB, IC50 = 6.0 μg/mL). Ref: M. Tsuda, et al, Tetrahedron, 1999, 55, 12543 O O

S

OH O O

HN

O N H

H N

H N

N O

O

O O

N H

H N

O O H N O

HO Br N H

N

O

1.9 Cyclic Peptides with Oxazole and Thiazole

163

407 Keramamide N Type: Cyclic peptides with oxazole. C53H75BrN10O15S Amorph. solid. Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 2.8 μg/mL, KB, IC50 = 7.5 μg/mL). Ref: M. Tsuda, et al, Tetrahedron, 1999, 55, 12543 O O

S

OH O O

O

HN

H N

N H

H N

N O

O

O

H N

O O

O

N

O

H N

N H

O

HO Br N H

408 Perthamide K Type: Cyclic peptides with oxazole. C45H64N10O15 Source: Lithistid sponge Theonella swinhoei (Solomon Is.). Pharm: Anti-inflammatory. Ref: C. Festa, et al, Tetrahedron, 2012, 68, 2851

H 2N

O

O

NH

O

O N H

NH OH

O

OH

O N

O

N H

N O O

HN H N

NH O

O

O O

1.9 Cyclic Peptides with Oxazole and Thiazole 409 Ascidiacyclamide Type: Cyclic peptides with oxazole and thiazole. C36H52N8O6S2 Prisms, (C6H6), mp 245–246 °C, mp 139–139.5 °C, [α]D25 = +164° (c = 0.466, CHCl3). Source: An unidentified ascidian. Pharm: Cytotoxic (PV4 cultured cells transformed with virus Polyoma sp.). Ref: Y. Hamamoto, et al, J. Chem. Soc., Chem. Commun., 1983, 323│ Y. Hamada, et al, Tet. Lett., 1985, 26, 3223│Y. In, et al, Acta Cryst. C, 1994, 50, 2015

164

1 Peptides

O S

N H

O

N

N

O HN

NH O N

N

H N

O

S O

410 Bistratamide A Type: Cyclic peptides with oxazole and thiazole. C27H34N6O4S2 Source: Ascidian Lissoclinum bistratum, Prochloron sp. Pharm: Cytotoxic (T24 cells, control SV40transformed hmn fibroblasts MRC5CV-1). Ref: B. M. Degnan, et al, JMC, 1989, 32, 1354 O O

S

N H

N

N

NH

HN

O

N

O

S

411 Bistratamide B Type: Cyclic peptides with oxazole and thiazole. C27H32N6O4S2 Source: Ascidian Lissoclinum bistratum, Prochloron sp. Pharm: Cytotoxic (T24 cells, control SV40transformed hmn fibroblasts MRC5CV-1, activity less so than Bistratamide A). Ref: B. M. Degnan, et al, JMC, 1989, 32, 1354 O O

N

S

N H

N

NH O

HN

O

N S

412 Bistratamide D Type: Cyclic peptides with oxazole and thiazole. C25H34N6O5S [α]D25 = −31° (c = 0.33, CHCl3). Source: Ascidian Lissoclinum bistratum. Pharm: Sedative; CNS system

1.9 Cyclic Peptides with Oxazole and Thiazole

165

depressant. Ref: M. P. Foster, et al, JOC, 1992, 57, 6671│L. J. Perez, et al, JNP, 2003, 66, 247

H O

O O

N H

N

N

NH

O

HN N

O

S

413 Bistratamide E Type: Cyclic peptides with oxazole and thiazole. C25H34N6O4S2 Glass, [α]D = −31° (c = 1, MeOH). Source: Ascidian Lissoclinum bistratum. Pharm: Cytotoxic (HCT116, IC50 = 7.9 μg/mL, weak). Ref: L. J. Perez, et al, JNP, 2003, 66, 247

H

3

O

O

S

N H

2

N

N

NH

O

HN N

O

S

414 Bistratamide F Type: Cyclic peptides with oxazole and thiazole. C25H36N6O5S Cream solid, [α]D = +23.2° (c = 1, MeOH). Source: Ascidian Lissoclinum bistratum. Pharm: Cytotoxic (HCT116, IC50 = 28 μg/mL, weak). Ref: M. P. Foster, et al, JOC, 1992, 57, 6671│ L. J. Perez, et al, JNP, 2003, 66, 247

H O

N

O O

N H

N

20 19

NH O

HN N S

O

166

1 Peptides

415 Bistratamide G Type: Cyclic peptides with oxazole and thiazole. C25H32N6O5S Solid, [α]D = −73.8° (c = 1, MeOH). Source: Ascidian Lissoclinum bistratum. Pharm: Cytotoxic (HCT116, IC50 = 5 μg/mL, weak). Ref: M. P. Foster, et al, JOC, 1992, 57, 6671│L. J. Perez, et al, JNP, 2003, 66, 247 O

O

O

N H

N

N

NH

O

HN N

O

S

416 Bistratamide H Type: Cyclic peptides with oxazole and thiazole. C25H32N6O4S2 Solid, [α]D = −92.9° (c = 1, MeOH). Source: Ascidian Lissoclinum bistratum. Pharm: Cytotoxic (HCT116, IC50 = 1.7 μg/mL). Ref: L. J. Perez, et al, JNP, 2003, 66, 247 O 2

3

O

S

N H

N

N

NH

O

HN N

O

S

417 Bistratamide I Type: Cyclic peptides with oxazole and thiazole. C25H36N6O6S Solid, [α]D = −122° (c = 0.5, MeOH). Source: Ascidian Lissoclinum bistratum. Pharm: Cytotoxic (HCT116, IC50 = 9 μg/mL, weak). Ref: L. J. Perez, et al, JNP, 2003, 66, 247 O

OH H O

NH

O

N H

N

NH O

HN N S

O

1.9 Cyclic Peptides with Oxazole and Thiazole

167

418 trans,trans-Ceratospongamide Type: Cyclic peptides with oxazole and thiazole. C41H49N7O6S Amorph. solid, [α]D = −39.2° (c = 0.52, CHCl3). Source: Red alga Ceratodictyon spongiosum (Indonesia) and sponge Sigmadocia symbiotica (symbiotic). Pharm: Toxic (brine shrimp, LD50 = 13–19 μmol/L); anti-inflammatory (hmn non-pancreatic phospholipase A2 inhibitor, ED50 = 32 nmol/L). Ref: L. T. Tan, et al, JOC, 2000, 65, 419 S N

N O

O HN

NH

O N

O

N

O

N H

O

419 cis,cis-Ceratospongamide Type: Cyclic peptides with oxazole and thiazole. C41H49N7O6S Amorph. solid, [α]D = −190° (c = 0.13, CHCl3). Source: Red alga Ceratodictyon spongiosum (Indonesia) and sponge Sigmadocia symbiotica (symbiotic). Pharm: Toxic (brine shrimp, LD50 = 13–19 μmol/L). Ref: L. T. Tan, et al, JOC, 2000, 65, 419│F. Yokokawa, et al, Synlett, 2001, 986 S N

N O

O HN

NH

O N

O

O

N N H

O

420 Comoramide A Type: Cyclic peptides with oxazole and thiazole. C34H48N6O6S Amorph. powder, [α]D = +0.5° (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

168

1 Peptides

O HO O

S

N H

NH NH

N HN

H N

O

O

O

O

421 Cyclodidemnamide Type: Cyclic peptides with oxazole and thiazole. C34H43N7O5S2 Solid, mp 114–118 °C, [α]D = +128.8° (c = 2.60, MeOH). Source: Ascidian Didemnum molle (Philippines). Pharm: Cytotoxic (HCT116, in vitro, ED50 = 16 μg/mL). Ref: S. G. Toske, et al, Tet. Lett., 1995, 36, 8355│C. D. J. Boden, et al, Tet. Lett., 1996, 37, 9111│ M. C. Norley, et al, Tet. Lett., 1998, 39, 3087│C. D. J. Boden, et al, JCS Perkin I, 2000, 883 O

H O

N H

N

N O

H N

NH N

O

S H O

HN

S

422 Dolastatin I Type: Cyclic peptides with oxazole and thiazole. C24H32N6O5S Amorph. powder, [α]D30 = −50° (c = 0.06, CHCl3). Source: Sea hare Dolabella auricularia (Japan waters). Pharm: Cytotoxic (HeLa-S3, IC50 = 12 μg/mL,). Ref: H. Sone, et al, Tetrahedron, 1997, 53, 8149│H. Kigoshi, et al, Tetrahedron, 1999, 55, 12301

O O

N

O

N H

N

H HN

NH O

N S

O

1.9 Cyclic Peptides with Oxazole and Thiazole

169

423 Leucamide A Type: Cyclic peptides with oxazole and thiazole. C29H37N7O6S Amorph. solid. Source: Calcareous sponge Leucetta microraphis (Australia). Pharm: Cytotoxic (HM02, GI50 = 5.2 μg/mL; HepG2, GI50 = 5.9 μg/mL; Huh7, GI50 = 5.1 μg/mL). Ref: S. Kehraus, et al, JOC, 2002, 67, 4989 O

S

O

N

N

HN

NH O

O

N

H N

N

O O

424 Lissoclinamide 2 Type: Cyclic peptides with oxazole and thiazole. C33H41N7O5S2 Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (L1210, IC50 = 10 μg/mL, borderline). Ref: J. M. Wasylyk, et al, JOC, 1983, 48, 4445│J. E. Biskupiak, et al, JOC, 1983, 48, 2304

O O

N

32

N H

H 7

S 10

N 11

N O

O

HN 14

N

H N

S O

425 Lissoclinamide 3 Type: Cyclic peptides with oxazole and thiazole. C33H41N7O5S2 Source: Ascidian Lissoclinum patella (North-western Australia). Pharm: Cytotoxic (L1210, IC50 = 10 μg/mL, borderline). Ref: J. M. Wasylyk, et al, JOC, 1983, 48, 4445│J. E. Biskupiak, et al, JOC, 1983, 48, 2304│ M. A. Rashid, et al, JNP, 1995, 58, 594

170

1 Peptides

O O

32

N H

N

H

S

7

10

N 11

O

HN

N

14

O

N

H N

S O

426 Patellamide A Type: Cyclic peptides with oxazole and thiazole. C35H50N8O6S2 Cryst. (C6H6), mp 228–229 °C, [α]D24 = +140.7° (c = 0.27, CHCl3). Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (L1210, IC50 = 2–4 μg/mL); cytotoxic (KB, IC50 = 3000 ng/mL); selective cytotoxicity (Corbett assay, zone differential < 250 zone units, no selective cytotoxicity); selective metal binding propties; MDR inhibitor. Ref: C. M. Ireland, et al, JOC, 1982, 47, 1807│J. E. Biskupiak, et al, JOC, 1983, 48, 2302│D. E. Williams, et al, JNP, 1989, 52, 732│Y. In, et al, CPB, 1993, 41, 1686│Y. In, et al, Acta Cryst. C, 1994, 50, 432│L. A.Morris, et al, Tetrahedron, 2001, 57, 3185│C.E.Salomon, et al, JNP, 2002, 65, 689 O

O

N

S

N H

N O

NH

HN

O N S

N

H N

O

O

427 Patellamide B Type: Cyclic peptides with oxazole and thiazole. C38H48N8O6S2 [α]D = +29.4° (c = 0.34, CH2Cl2). Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (NCI’s 60 hmn tumor cell line panel, average IC50 = 48 μmol/L); cytotoxic (L1210, IC50 = 2–4 μg/mL); cytotoxic (KB, IC50 > 4000 ng/mL); selective cytotoxicity (Corbett assay, zone differential < 250 zone units, no selective cytotoxicity); MDR inhibitor. Ref: C. M. Ireland, et al, JOC, 1982, 47, 1807│J. E. Biskupiak, et al, JOC, 1983, 48,

1.9 Cyclic Peptides with Oxazole and Thiazole

171

2302│D. E. Williams, et al, JNP, 1989, 52, 732│ M. A. Rashid, et al, JNP, 1995, 58, 594│C.E.Salomon, et al, JNP, 2002, 65, 689 O O

S

N H

N

N O

NH

HN

O N

N

H N

S

O O

428 Patellamide C Type: Cyclic peptides with oxazole and thiazole. C37H46N8O6S2 [α]D = +19° (c = 0.21, CH2Cl2). Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (L1210, IC50 = 2–4 μg/mL); cytotoxic (KB, IC50 = 6000 ng/mL); selective cytotoxicity (Corbett assay, zone differential < 250 zone units, no selective cytotoxicity); selective metal binding propties; MDR inhibitor. Ref: C. M. Ireland, et al, JOC, 1982, 47, 1807│ D. E. Williams, et al, JNP, 1989, 52, 732│C.E.Salomon, et al, JNP, 2002, 65, 689

O O N

S

N H

N O

NH

HN

O N S

N

H N

O O

429 Patellamide D Type: Cyclic peptides with oxazole and thiazole. C38H48N8O6S2 mp 144–145 °C, [α]D = +32° (c = 0.37, CHCl3). Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (T24 tumor cells, 50 μg/mL, incorporation of [methyl-3H] thymidine, percentage of incorporation of untreated cells = 80%). Ref: B. M. Degnan, et al, JMC, 1989, 32, 1349│F. J. Schmitz, et al, JOC, 1989, 54, 3463

172

1 Peptides

O O

S

N H

N

N O

NH

HN

O N S

N

H N

O

O

430 Patellamide E Type: Cyclic peptides with oxazole and thiazole. C39H50N8O6S2 Amorphous, [α]D25 = +48.6° (c = 0.58, CHCl3). Source: Ascidian Lissoclinum patella (Singapore). Pharm: Cytotoxic (in vitro, hmn colon tumor cells, IC50 = 125 μg/mL). Ref: L. A. McDonald, et al, JNP, 1992, 55, 376 O O N

S

N H

N O HN

NH O N

N H N

O

S O

431 Patellamide F Type: Cyclic peptides with oxazole and thiazole. C37H46N8O6S2 Amorphous solid, [α]D = +40° (c = 0.1, MeOH). Source: Ascidian Lissoclinum patella (North-western Australia). Pharm: Cytotoxic (NCI’s 60 hmn tumor cell line panel, average IC50 = 13 μmol/L). Ref: M. A. Rashid, et al, JNP, 1995, 58, 594

1.9 Cyclic Peptides with Oxazole and Thiazole

173

O O

S

N H

N

N O

NH

HN

O N

N

H N

S

O O

432 Patellamide G Type: Cyclic peptides with oxazole and thiazole. C38H50N8O7S2 Amorph. solid, [α]D = +40.6° (c = 0.35, MeOH). Source: Ascidian Lissoclinum patella (Pohnpei I., Federated States of Micronesia). Pharm: Anti-MDR (vinblastine-resistant CCRF-CEM hmn leukemic lymphoblasts, IC50 = 60 μmol/L). Ref: X. Fu, et al, JNP, 1998, 61, 1547 O

OH

NH

O

S

N H

N O HN

NH O N S

N

H N

O

O

433 Ulithiacyclamide 2 Type: Cyclic peptides with oxazole and thiazole. C32H42N8O6S4 Oil, [α]D25 = +62.4° (c = 2.9, CH2Cl2). Source: Ascidian Lissoclinum patella (North-western Australia), an unidentified ascidian (Rodda Reef, Queensland, Australia). Pharm: Cytotoxic (L1210, IC50 = 0.35 μg/mL, CEM, IC50 = 0.01 μg/mL); selective metal binding properties; cytotoxic (KB, IC50 = 35 ng/mL); cytotoxic (NCI’s 60 hmn tumor cell line panel, average IC50 = 3 μmol/L); selective cytotoxicity (Corbett assay). Ref: C. Ireland, et al, JACS, 1980, 102, 5688│C. M. Ireland, et al, JOC, 1982, 47, 1807│J. E. Biskupiak, et al, JOC, 1983, 48, 2302│T. Ishida, et al, JOC, 1989, 54, 5337│D. E. Williams, et al, JNP, 1989, 52, 732│ M. A. Rashid, et al, JNP, 1995, 58, 594

174

1 Peptides

O S

N H

O N

N O

NH

S

HN

S

O N

N

H N

S

O O

434 Ulithiacyclamide B Type: Cyclic peptides with oxazole and thiazole. C35H40N8O6S4 Amorph. solid, [α]D24.5 = +117° (c = 0.17, MeOH). Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (KB, IC50 = 17 ng/mL), selective cytotoxicity (Corbett assay, zone differential < 250 zone units, no selective cytotoxicity). Ref: D. E. Williams, et al, JNP, 1989, 52, 732

O S

N H

O N

N O

NH

S

HN

S

O N S

N

H N

O O

435 Ulithiacyclamide F Type: Cyclic peptides with oxazole and thiazole. C35H42N8O7S4 Amorph. solid, [α]D = +29.6° (c = 0.27, MeOH). Source: Ascidian Lissoclinum patella (Pohnpei I., Federated States of Micronesia). Pharm: Anti-MDR (vinblastine-resistant CCRFCEM hmn leukemic lymphoblasts, IC50 = 44 μmol/L). Ref: X. Fu, et al, JNP, 1998, 61, 1547

1.9 Cyclic Peptides with Oxazole and Thiazole

O

OH

O

NH

S

O

S

N O

S

HN

S

N H

NH

N

175

N

H N

O

O

436 Ulithiacyclamide G Type: Cyclic peptides with oxazole and thiazole. C35H42N8O7S4 Amorph. solid, [α]D = +25.6° (c = 0.18, MeOH). Source: Ascidian Lissoclinum patella (Pohnpei I., Federated States of Micronesia). Pharm: Anti-MDR (vinblastine-resistant CCRFCEM hmn leukemic lymphoblasts, IC50 = 90 μmol/L). Ref: X. Fu, et al, JNP, 1998, 61, 1547

O

O

N H

N S

HN O N S

S N O NH

S HN

H N O

O

OH

437 Venturamide A Type: Cyclic peptides with oxazole and thiazole. C21H24N6O4S2 Glass, [α]D25 = +53.4° (c = 0.001, MeOH). Source: Cyanobacterium Oscillatoria sp. (Panama). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 8.2 μmol/L). Ref: R. G. Linington, et al, JNP, 2007, 70, 397

176

1 Peptides

O

O

S

N H

N

N HN

NH

O

N O S

438 Venturamide B Type: Cyclic peptides with oxazole and thiazole. C22H26N6O5S2 Glass, [α]D25 = +53.6° (c = 0.004, MeOH). Source: Cyanobacterium Oscillatoria sp. (Panama). Pharm: Antiplasmodial (Plasmodium falciparum, IC50 = 5.6 μmol/L). Ref: R. G. Linington, et al, JNP, 2007, 70, 397 O

O

HO S

N H

N

N

HN

NH

O

N O S

1.10 Cyclic Peptides with Thiazole 439 Calyxamide A Type: Cyclic peptides with thiazole. C45H61N11O12S Source: Lithistid sponge Discodermia calyx (Shikine-Jima I., Japan). Pharm: Antiproliferative (moderate). Ref: J. W. Blunt, et al, NPR, 2014, 31, 160 H N

H

O N H

O O

O

N H

HN

HN

O

O

O N

O

OH

H N

NH

H N

O

NH2

O

H N

S

O

1.10 Cyclic Peptides with Thiazole

177

440 Calyxamide B Type: Cyclic peptides with thiazole. C45H61N11O12S Source: Lithistid sponge Discodermia calyx (Shikine-Jima I., Japan). Pharm: Antiproliferative (moderate). Ref: J. W. Blunt, et al, NPR, 2014, 31, 160 O

H N

H

N H

O O

O

N H

HN

HN

H N O

O

O NH

H N

O

NH2

O

H N

N O

S

O

OH

441 Comoramide B Type: Cyclic peptides with thiazole. C34H50N6O7S Amorph. powder, [α]D = −100° (c = 0.05, 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 HO O

NH NH O O

S

N H

N HN

H N

O

O

442 Cycloforskamide Type: Cyclic peptides with thiazole. C51H80N12O11S3 Source: Notapsid Pleurobranchus forskalii (Ishigaki I., Okinawa). Pharm: Cytotoxic (mild). Ref: M. Serova, et al, Mar. Drugs, 2013, 11, 944

178

1 Peptides

OH OH

H N

H N

H N

H N S

O

O

O

O

O

N

N NH

O N

H N

S

O

O

N H

N

N

O

S

443 Dolastatin 3 Type: Cyclic peptides with thiazole. C29H40N8O6S2 Amorph. solid, mp 133–137 °C, [α]D26 = −35.5° (c = 0.09, MeOH). Source: Cyanobacterium Lyngbya majuscula, sea hares Dolabella auricularia (Indian Ocean) and Aplysia pulmonica. Pharm: Cytotoxic (P388, ED50 = 1 × 10-4–1 × 10-7 μg/mL) (Pettit, 1982); cytotoxic (PS leukemia cells, ED50 = 0.16–0.17 μg/mL) (Pettit, 1987); HIV-1 integrase inhibitor. Ref: G. R. Pettit, et al, JACS, 1982, 104, 905; 1987, 109, 7581 O N O

O

N H

NH2

H N O

NH S

N

O N

H N

S

O

444 Homodolastatin 3 Type: Cyclic peptides with thiazole. C30H42N8O6S2 White solid. Source: Cyanobacterium Lyngbya majuscula (Palau, Oceania). Pharm: Anti-HIV (HIV-1 integrase inhibitor). Ref: S. S. Mitchell, et al, JNP, 2000, 63, 279 O N O

O

N H

NH2

H N O

NH N

O N S

H N O

S

1.10 Cyclic Peptides with Thiazole

179

445 Keenamide A Type: Cyclic peptides with thiazole. C30H48N6O6S Off-white powder, [α]D = +24° (c = 0.3, MeOH). Source: Notapsid Pleurobranchus forskalii. Pharm: Cytotoxic. Ref: K. J. Wesson, et al, JNP, 1996, 59, 629

O

O

O

N H

NH

NH H

O S

N

O

15

16

N

N H

O

H

446 Keramamide F Type: Cyclic peptides with thiazole. C43H56N10O11S Colorless solid, mp 187 °C (dec), [α]D21 = −25° (c = 0.86, MeOH). Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Cytotoxic (KB, IC50 = 1.4 μg/mL; L1210, IC50 = 2.0 μg/mL). Ref: F. Itagaki, et al, JOC, 1992, 57, 5540 H O

O N H

OH

O

H H N

N H

O O

N H

HN

H N

H 13

O

H

O

O

NH

H N

N O

O

S

N H

447 Keramamide G Type: Cyclic peptides with thiazole. C43H56N10O11S Solid, [α]D21 = +10° (c = 0.12, MeOH). Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Cytotoxic (weak, IC50 ≈ 10 μg/mL). Ref: J. Kobayashi, et al, Tetrahedron, 1995, 51, 2525

180

1 Peptides

H O

O N H

N H

OH

O

H H N O

N H

HN

O

H N 13

O

H H

O

O

NH

H N

N

O

S

O N H

448 Keramamide H Type: Cyclic peptides with thiazole. C43H57BrN10O12S Solid, [α]D20 = −42° (c = 0.055, MeOH). Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Cytotoxic (weak, IC50 ≈ 10 μg/mL). Ref: J. Kobayashi, et al, Tetrahedron, 1995, 51, 2525

O

O N H

N H

OH

O

N H

HN

O

H N 13

O

N

O

S

O

2'

N H

O

O NH

H N

5'

HO

O

H N

Br

449 Keramamide J Type: Cyclic peptides with thiazole. C43H58N10O11S Solid, [α]D18 = +8.4° (c = 0.1, MeOH). Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Cytotoxic (weak, IC50 ≈ 10 μg/mL). Ref: J. Kobayashi, et al, Tetrahedron, 1995, 51, 2525│J. A. Sowinski, et al, Chem. Commun., 1999, 981

O

O N H

OH

O

H N

N H

O O

HN

2'

H N 13

O

O

O NH

H N

5'

N H

N H

N O

S

O

1.10 Cyclic Peptides with Thiazole

181

450 Keramamide K Type: Cyclic peptides with thiazole. C44H60N10O11S Amorph. solid, [α]D28 = −25° (c = 0.1, MeOH). Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Cytotoxic (L1210, IC50 = 0.72 μg/mL, KB, IC50 = 0.42 μg/mL). Ref: H. Uemoto, et al, Tetrahedron, 1998, 54, 6719

O

O N H

N H

OH

O

H N O

13

O

HN

O

N

O

S

O

2'

O

O NH

H N

5'

N 1'

H N

N H

451 Kororamide Type: Cyclic peptides with thiazole. C45H64N10O10S2 White solid. Source: Cyanobacterium Lyngbya majuscula (Palau, Oceania). Pharm: Anti-HIV (HIV-1 integrase inhibitor). Ref: S. S. Mitchell, et al, JNP, 2000, 63, 279

HN

O

H

OH

H N

O

S

O

N

NH NH

O N O

S

O

O NH2

N

HN HN O

OH

452 Marthiapeptide A Type: Cyclic peptides with thiazole. C30H31N7O3S4 Colorless needle crystals, mp 115–116 °C, [α]D25 = +94° (c = 0.8, MeOH). Source: Marine-derived bacterium Marinactinospora thermotolerans SCSIO 00652 (deep sea, sediment, South China Sea). Pharm: Antibacterial (Micrococcus luteus, MIC = 2.0 μg/mL, control Erythromycin, MIC < 1.0 μg/mL, control Kanamycin, MIC = 32.0 μg/mL; Staphylococcus aureus ATCC 29213, MIC = 8.0 μg/mL, Erythromycin, MIC = 16.0 μg/mL, Kanamycin,

182

1 Peptides

MIC = 8.0 μg/mL; Bacillus subtilis ATCC 6633, MIC = 4.0 μg/mL, Erythromycin, MIC < 1.0 μg/mL, Kanamycin, MIC < 1.0 μg/mL; Bacillus thuringiensis, MIC = 2.0 μg/mL, Erythromycin, MIC < 1.0 μg/mL, Kanamycin, MIC = 4.0 μg/mL; Aeromonas hydrophila subsp. hydrophila ATCC7966, MIC > 128.0 μg/mL, Erythromycin, MIC = 4.0 μg/mL, Kanamycin, MIC < 1.0 μg/mL; Escherichia coli ATCC 25922, MIC > 128.0 μg/mL, Erythromycin, MIC = 32.0 μg/mL, Kanamycin, MIC = 16.0 μg/mL; Escherichia coli DH5α, MIC > 128.0 μg/mL, Erythromycin, MIC = 64.0 μg/mL, Kanamycin, MIC = 32.0 μg/mL); cytotoxic (SRB method, SF268, IC50 = (0.38 ± 0.02)μmol/L, control Cisplatin, IC50 = (4.76 ± 0.27)μmol/L; MCF7, IC50 = (0.43 ± 0.005)μmol/L, Cisplatin, IC50 = (3.99 ± 0.13)μmol/L; NCI-H460, IC50 = (0.47 ± 0.003)μmol/L, Cisplatin, IC50 = (2.91 ± 0.18)μmol/L; HepG2, IC50 = (0.52 ± 0.01)μmol/L, Cisplatin, IC50 = (2.45 ± 0.07) μmol/L). Ref: X. Zhou, et al, JNP, 2012, 75, 2251 O

S S

H N

N

N

O N

O

S

N

NH

NH

S

453 Mollamide A Type: Cyclic peptides with thiazole. C42H61N7O7S Prisms (CH2Cl2/petrol), mp 154–156 °C, [α]D = −2.75° (c = 0.08, CHCl3). Source: Ascidian Didemnum molle (Great Barrier Reef). Pharm: Cytotoxic (P388, IC50 = 1 μg/mL, A549, IC50 = 2.5 μg/mL, HT29, IC50 = 2.5 μg/mL, CV-1,IC50 = 2.5 μg/mL); RNA synthesis inhibitor (IC50 = 1 μg/mL). Ref: A. R. Carroll, et al, Aust. J. Chem., 1994, 47, 61│B. McKeever, et al, Tet. Lett., 1999, 40, 9317

O N O

O

N H

S

N O

HN

H N

H N

O O

O

N

1.10 Cyclic Peptides with Thiazole

183

454 Oriamide Type: Cyclic peptides with thiazole. C44H55N9O15S2 Amorphous powder (Na salt). Source: Lithistid sponge Theonella sp. (South Africa). Pharm: Cytotoxic. Ref: L. Chill, et al, Tetrahedron, 1997, 53, 16147 OH O

H N

N H

O

OH

O

H N

N H

O

H N

O O O H S O S O

HN O HN

O NH

N O

OH

455 Preulicyclamide Type: Cyclic peptides with thiazole. C33H41N7O6S2 [α]D = +5.4° (c = 0.24, CHCl3). Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic (KB, IC50 = 10000 ng/mL); selective cytotoxicity (Corbett assay, zone differential < 250 zone units, no selective cytotoxicity). Ref: D. F. Sesin, et al, Bull. Soc. Chim. Belg., 1986, 95, 853│ D. E. Williams, et al, JNP, 1989, 52, 732 O S

N

HO N O

H

H

N O H

N O

H

N

N

N

S O

456 Preulithiacyclamide Type: Cyclic peptides with thiazole. C32H46N8O8S4 Amorphous. powder, mp 178–181 °C. Source: Ascidian Lissoclinum patella (Palau, Oceania). Pharm: Macrophage scavenger receptor (MSR) inhibitor. Ref: A. D. Patil, et al, Nat. Prod. Lett., 1997, 9, 181

184

1 Peptides

O HO O

NH

H N

S

N H

N O

S S

O N S

N H HN

H N

O OH

O

457 Scleritodermin A Type: Cyclic peptides with thiazole. C42H55N7O13S2 Off–yellow powder (Na salt), [α]D = −41° (c = 0.1, MeOH) (Na salt). Source: Lithistid sponge Scleritoderma nodosum (Northwest side of Olango I., Cebu, Philippines; Milne Bay, Papua New Guinea). Pharm: Cytotoxic (HCT116, IC50 = 1.9 μmol/L; HCT116/VM46 multidrugresistant colon cancer, IC50 = 5.6 μmol/L; A2780, IC50 = 0.940 μmol/L; SKBR3, IC50 = 0.670 μmol/L); cytotoxic (cell cycle analysis in A2780 cells, treated by 1.3 μmol/L scleritodermin A for 24 h, a G2/M block yielded, further study found to inhibit GTP-induced tubulin polymerization by 50% at 10 μmol/L); induction of apoptosis (after 24 h drug exposure at a concentration close to its cytotoxic IC50, Scleritodermin A caused a 5.5-fold increase in induction of apoptosis over the control). Ref: E. W. Schmidt, et al, JNP, 2004, 67, 475│S. Liu, et al, Org. Lett., 2008, 10, 3765 (stereochem. Revised)│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2644 (rev) OH

S O N H

O

H N 14S

O

N

4E 2E

O

O O

N N H

N O O

O O HO

S O

NH

1.10 Cyclic Peptides with Thiazole

185

458 Tawicyclamide A Type: Cyclic peptides with thiazole. C39H50N8O5S3 Colorless solid, [α]D25 = −15.0° (c = 0.427, CHCl3). Source: Ascidian Lissoclinum patella (Philippines). Pharm: Cytotoxic (hmn colontumor cells in vitro, weak). Ref: L. A. McDonald, et al, JOC, 1992, 57, 4616 O S

N H

S N

N O HN

NH O

O

N

N

H N

S O

459 Tawicyclamide B Type: Cyclic peptides with thiazole. C36H52N8O5S3 Colorless solid, [α]D25 = +2.1° (c = 0.347, CHCl3). Source: Ascidian Lissoclinum patella (Philippines). Pharm: Cytotoxic (hmn colontumor cells in vitro, weak). Ref: L. A. McDonald, et al, JOC, 1992, 57, 4616 O S N

S

N H

N O HN

NH O N

O N

H N

S O

460 Trunkamide A Type: Cyclic peptides with thiazole. C43H63N7O8S [α]D25 = −231° (c = 0.06, CHCl3). Source: Ascidian Lissoclinum sp. Pharm: Antineoplastic. Ref: A. R. Carroll, et al, Aust. J. Chem., 1996, 49, 659│P. Wipf, et al, Tet. Lett., 1999, 40, 5165│P. Wipf, et al, JOC, 2000, 65, 1037

186

1 Peptides

O S

N H O

N HN

N O OO

H N

O

NH O

NH O

461 Ulicyclamide Type: Cyclic peptides with thiazole. C33H39N7O5S2 Oil, [α]D25 = +35.7° (c = 2.3, CH2Cl2). Source: Ascidian Lissoclinum patella. Pharm: Cytotoxic. Ref: C. Ireland, et al, JACS, 1980, 102, 5688

O O

32

N H

N

H

S

7

10

N 11

O

HN

N

14

O

N

H N

S O

462 Ulithiacyclamide E Type: Cyclic peptides with thiazole. C35H44N8O8S4 Amorph. solid, [α]D = +4.9° (c = 0.82, MeOH). Source: Ascidian Lissoclinum patella (Pohnpei I., Federated States of Micronesia). Pharm: Anti-MDR (vinblastine-resistant CCRF-CEM hmn leukemic lymphoblasts, IC50 = 112 μmol/L). Ref: X. Fu, et al, JNP, 1998, 61, 1547

OH

O

O

NH S

HN O N S

N H

S N O NH

S HN

H N O

O

OH

1.12 Anabaenopeptins

187

1.11 Enniatins 463 Enniatin B Type: Enniatins. C33H57N3O9 Cryst. (petrol), mp 174–176 °C, [α]D20 = −107.9° (c = 0.63, CHCl3). Source: Mangrove-derived fungus Halosarpheia sp. 732 from an unidentified mangrove. Pharm: Ionophore. Ref: Y. Lin, et al, Aust. J. Chem., 2002, 55, 225

O

N O O

O

O O

O

N

O O

N

464 Enniatin D Enniatin B4 Type: Enniatins. C34H59N3O9 Powder, mp 140–143 °C, [α]D25 = −88.9° (c = 0.32, CHCl3). Source: Mangrove-derived fungus Halosarpheia sp. 732 from an unidentified mangrove. Pharm: Ionophore; ACAT inhibitor. Ref: Y. Lin, et al, Aust. J. Chem., 2002, 55, 225

O

N O O

O N

O O

O

N

O O

1.12 Anabaenopeptins 465 Anabaenopeptin A Type: Anabaenopeptins. C44H57N7O10 Amorph. powder, [α]D30 = −64.1° (c = 0.05, MeOH). Source: Cyanobacteria Anabaena flos-aquae NRC525.17 and Anabaena sp. 90. Pharm: Antibiotic. Ref: K. Harada, et al, Tet. Lett., 1995, 36, 1511; 1515│K. Fujii, et al, Tetrahedron, 2002, 58, 6863│L. F. Morrison, et al, Peptides (N.Y.), 2006, 27, 10

188

1 Peptides

HO

O

H N N

N H

O

O O

H N

O

H N

OH

O

O

OH

HN

NH

466 Anabaenopeptin B Type: Anabaenopeptins. C41H60N10O9 Amorph. powder, [α]D30 = −71.4° (c = 0.05, MeOH). Source: Cyanobacteria Anabaena flos-aquae NRC525-17 (fresh water), Planktothrix agardhii HUB011 and Oscillatoria agardhii NIES 204. Pharm: Antibiotic. Ref: K. Harada, et al, Tet. Lett., 1995, 36, 1511; 1515│ M. Murakami, et al, Phytochemistry, 1997, 44, 449│K. Fujii, et al, Tetrahedron, 2002, 58, 6863│ L. F. Morrison, et al, Peptides (N.Y.), 2006, 27, 10 HO

O

H N N

O O

O

N H

H N

H N

OH

O

O

HN

O

HN NH

H2N

NH

467 Anabaenopeptin C Type: Anabaenopeptins. C41H60N8O9 [α]D30 = −65.2° (c = 0.05, MeOH). Source: Cyanobacterium Anabaena sp. 90. Pharm: Antibiotic. Ref: K. Fujii, et al, Tetrahedron, 2002, 58, 6863 HO

O

H N N

O O HN

O

N H

H N

H N

O OH

O

O NH

NH2

1.12 Anabaenopeptins

189

468 Anabaenopeptin D Type: Anabaenopeptins. C44H57N7O9 [α]D30 = −50° (c = 0.05, MeOH). Source: Cyanobacterium Anabaena sp. 202A2. Pharm: Antibiotic. Ref: K. Fujii, et al, Tetrahedron, 2002, 58, 6863 HO

O

H N N

O

N H

O

O

H N

H N

O OH

O

O

HN

NH

469 Anabaenopeptin G Type: Anabaenopeptins. C49H67N7O11 Amorph. solid, [α]D = −27° (c = 0.2, MeOH). Source: Cyanobacterium Oscillatoria agardhii [Syn. Planktothrix agardhii] NIES 595. Pharm: Carboxypeptidase A inhibitor. Ref: Y. Itou, et al, Bioorg. Med. Chem. Lett., 1999, 9, 1243

HO

O

H N N

O O

HN

H

O

N H H

H N

H N O

O

OH

OH

O NH

HO

470 Anabaenopeptin H Type: Anabaenopeptins. C46H70N10O10 Amorph. solid, [α]D = −24.4° (c = 0.08, MeOH). Source: Cyanobacterium Oscillatoria agardhii NIES 595. Pharm: Carboxypeptidase A inhibitor. Ref: Y. Itou, et al, Bioorg. Med. Chem. Lett., 1999, 9, 1243

190

1 Peptides

NH HO

O

H N N

O

HN

N H H

O

O H

H N

N H

H N O

O

NH2

OH

O NH

HO

471 Anabaenopeptin I Type: Anabaenopeptins. C38H61N7O9 Powder, [α]D = −30° (c = 0.1, MeOH). Source: Cyanobacterium Aphanizomenon flos-aquae. Pharm: Carboxypeptidase A inhibitor. Ref: M. Murakami, et al, JNP, 2000, 63, 1280 HO

O

H N N

O O

O

N H

H N

H H N

O OH

O

O

HN

NH

472 Anabaenopeptin J Type: Anabaenopeptins. C41H59N7O9 Powder, [α]D = −51.5° (c = 0.1, MeOH). Source: Cyanobacterium Aphanizomenon flos-aquae NIES 81. Pharm: Carboxypeptidase A inhibitor. Ref: M. Murakami, et al, JNP, 2000, 63, 1280 HO

O

H N

N

O O HN

O

N H

H N

H H N

O OH

O

O NH

473 Anabaenopeptin T Type: Anabaenopeptins. C45H67N7O10 Amorph. powder, [α]D = −14.1° (c = 0.1, MeOH). Source: An unidentified cyanobacterium. Pharm: Carboxypeptidase A inhibitor. Ref: S. Kodani, et al, FEMS Microbiol. Lett., 1999, 178, 343

1.12 Anabaenopeptins

HO

O

H N N

O

O O

H N O

H O

OH

O

H

HN

H N

N H

191

NH

HO

474 Brunsvicamide B Type: Anabaenopeptins. C46H66N8O8 Amorph. solid, [α]D24 = −52.4° (c = 0.37, MeOH). Source: Cyanobacterium Tychonema sp. Pharm: Antituberculosis (Mycobacterium tuberculosis, protein tyrosine phosphatase B inhibitor). Ref: D. Müller, et al, JMC, 2006, 49, 4871

H

H N

N

O

H N

H N

N H

O O

O

O

O

OH

O

HN

NH

N H

475 Brunsvicamide C Type: Anabaenopeptins. C45H64N8O10 Amorph. solid, [α]D24 = −76.3° (c = 0.42, MeOH). Source: Cyanobacterium Tychonema sp. Pharm: Antituberculosis (Mycobacterium tuberculosis, protein tyrosine phosphatase B inhibitor). Ref: D. Müller, et al, JMC, 2006, 49, 4871 O

H N

O

N

O O HN

NH H

O

O

N H

O NH

H N

H H N O

O OH

192

1 Peptides

476 Keramamide A Type: Anabaenopeptins. C49H63ClN8O9 [α]D20 = −190° (c = 0.03, MeOH). Source: Lithistid sponge Theonella sp. Pharm: Calcium ATPase inhibitor. Ref: J. Kobayashi, et al, JCS Perkin I, 1991, 2609

O

H N

N

O O

HO

N H

O

H N

H N

O OH

O

O NH

HN N H

Cl

477 Keramamide L Type: Anabaenopeptins. C49H63ClN8O8 Amorph. solid, [α]D22 = −60° (c = 0.1, MeOH). Source: Lithistid sponge Theonella sp. (off Kerama I., Okinawa). Pharm: Cytotoxic (L1210, in vitro IC50 = 0.46 μg/mL, KB in vitro, IC50 = 0.9 μg/mL). Ref: H. Uemoto, et al, Tetrahedron, 1998, 54, 6719

5'

Cl

N HN

O

HN

O HN

NH O

O HN

O

N H

O

COOH N H

478 Konbamide Konbanamide Type: Anabaenopeptins. C40H61BrN8O9 [α]D21 = −43° (c = 0.042, MeOH). Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Calmodulin antagonist. Ref: J. Kobayashi, et al, J. Chem. Soc., Chem. Commun., 1991, 1050│U. Schmidt, et al, Angew. Chem., Int. Ed. Engl., 1996, 35, 1336

1.12 Anabaenopeptins

N O

193

NH O

O

NH

HN

O

O O

HO Br HN N H

OH

N H

N H

O

479 Nodulapeptin A Type: Anabaenopeptins. C44H63N7O13S Amorph., [α]D26 = −43.5° (c = 0.03, MeOH). Source: Cyanobacterium Nodularia spumigena AV1. Pharm: Phycotoxin; hepatotoxin. Ref: K. Fujii, et al, Tet. Lett., 1997, 38, 5525

S

O O O

H N N

O O

HO

N H

O

H N

H N

O H

O

OH

O N H

HN O O

480 Nodulapeptin B Type: Anabaenopeptins. C44H63N7O12S Amorph., [α]D26 = −44.7° (c = 0.03, MeOH). Source: Cyanobacterium Nodularia spumigena AV1. Pharm: Phycotoxin; hepatotoxin. Ref: K. Fujii, et al, Tet. Lett., 1997, 38, 5525

S

O

H N N

O O

HO

HN O O

O

O

N H

O N H

H N

H N O

O H

OH

194

1 Peptides

481 Oscillamide B Type: Anabaenopeptins. C41H60N10O9S Amorph. solid, [α]D25 = −83° (c = 0.2, MeOH). Source: Cyanobacteria Planktothrix agardhii and Planktothrix rubescens. Pharm: Protein phosphatase inhibitor. Ref: T. Sano, et al, JNP, 2001, 64, 1052 NH

S HO

O

H N N

O O

N H

O

N H

H N

H N O

O

NH2

OH

O NH

HN

482 Oscillamide C Type: Anabaenopeptins. C49H68N10O10 Amorph. solid, [α]D25 = −111° (c = 0.15, MeOH). Source: Cyanobacterium Planktothrix rubescens. Pharm: Protein phosphatase inhibitor. Ref: T. Sano, et al, JNP, 2001, 64, 1052 NH HO H N N

O O

HO

HN

H O

O

N H

N H

H N

H N O

O

NH2

OH

O NH

483 Oscillamide Y Type: Anabaenopeptins. C45H59N7O10 Amorph. solid, [α]D = −58.7° (c = 0.1, MeOH). Source: Cyanobacterium Oscillatoria agardhii. Pharm: Chymotrypsin inhibitor. Ref: T. Sano, et al, Tet. Lett., 1995, 36, 5933│K. Fujii, et al, Tetrahedron, 2000, 56, 725

1.13 Destruxins

HO H

H N N

O

O O

O

N H

O OH

O OH

O

HN

H N

H N

195

NH

1.13 Destruxins 484 Destruxin E chlorohydrin Type: Destruxins. C29H48ClN5O8 Glass. Source: Marine-derived fungus Beauveria felina from green alga Caulerpa sp. (off coast of Brazil). Pharm: Insecticide. Ref: S. Gupta, et al, JCS Perkin I, 1989, 2347│S. P. Lira, et al, J. Antibiot., 2006, 59, 553 H N

N

O

O O

O

Cl

O

N H O

N

N H

O

OH

485 Roseocardin Type: Destruxins. C31H53N5O7 Cryst., [α]D = −206.4° (c = 1, MeOH). Source: Marinederived fungus Beauveria felina. Pharm: Cardiotonic. Ref: A. Tsunoo, et al, J. Antibiot., 1997, 50, 1007│S. P. Lira, et al, J. Antibiot., 2006, 59, 553 O O

HN

N

O

O

O

O

H N

O

H

N

NH

196

1 Peptides

486 Roseotoxin B Type: Destruxins. C30H49N5O7 Cryst. (C6H6/hexane), mp 200–202 °C, [α]D25 = −235° (EtOH). Source: Marine-derived fungus Beauveria felina. Pharm: Cardioactive; inotropic; mycotoxin. Ref: S. P. Lira, et al, J. Antibiot., 2006, 59, 553 O O

HN

N

O

O

O

O

O

H

N

N

NH

1.14 Simple Cyclic Depsipeptides 487 Alternaramide Type: Simple cyclic depsipeptides. C33H40N4O6 Powder, [α]D25 = −6° (c = 0.53, MeOH). Source: Marine-derived fungus Alternaria sp. SF-5016 (sediment sample, Korea waters). Pharm: Antibacterial (Staphylococcus aureus and Bacillus subtilis, weak); protein tyrosine phosphatase 1B (PTP1B) inhibitor. Ref: M. -Y. Kim, et al, JNP, 2009, 72, 2065 O O N H O HN O

H

O

HN

O

N

488 Alterobactin A Type: Simple cyclic depsipeptides. C36H53N11O18 Grey-white solid. Source: Marine bacterium Alteromonas luteoviolacea. Pharm: Siderophore (exceptional affinity for ferric ion, Ka = 1049–1053). Ref: R. T. Reid, et al, Nature, 1993, 366, 455│J. Deng, et al, JACS, 1995, 117, 7824│J. Deng, et al, Synthesis, 1998, 627

1.14 Simple Cyclic Depsipeptides

COOH

HO O

NH

O

HOOC

H N H

O O

O OH

N H

H

HO

NH

197

HN H N

O

OH

HO

O

H2N

O

H N

NH O N H

H 2N

489 Antibiotic IB 01212 Type: Simple cyclic depsipeptides. C56H88N8O10 Powder, [α]D = −106° (c = 1, CHCl3). Source: Marine-derived fungus Clonostachys sp. ESNA-A009 from an unidentified sponge (Japan waters). Pharm: Cytotoxic (LNCaP, SKBR3, HT29, and HeLa in panel of 14 different hmn tumour cell lines, GI50 is in order of 1.0 × 10-8 mol/L). Ref: L. J. Cruz, et al, JOC, 2006, 71, 3335; 3339

N

H N

O N

N

O

O O

O N

O

O

O

O N O

N H

N

490 Aplidine Dehydrodidemnin B; Plitidepsin Type: Simple cyclic depsipeptides. C57H87N7O15 Solid, mp 152–160 °C, [α]D = −95.9° (c = 1.8, CHCl3). Source: Ascidians Trididemnum solidum (Little San Salvador I., Bahamas) and Aplidium albicans (Mediterranean Sea). Pharm: Immunosuppressive (MLR assay, IC50 = 0.38 nmol/L); cytotoxic (P388, IC50 = 0.18 nmol/L); antineoplastic (phase II clin. Trial, 2002, granted orphan drug status by FDA, 2004, for treatment of acute lymphoblastic leukaemia and multiple myeloma); inhibits vascular endothelial growth factor (VEGF) secretion. Ref: F. J. Schmitz, et al, JNP, 1991, 54, 1469│R. Sakai, et al, JMC, 1996, 39, 2819│B. Liang, et al, JACS, 2001, 123, 4469│J. Jimeno, et al, Mar. Drugs, 2004, 1, 14 (rev)│E. F. Brandon, et al, Invest. New Drugs, 2007, 25, 9│T. F. Molinski, et al, JNP, 2011, 74, 882

198

1 Peptides

H

O

O O

O

N

O

H

N H H

NH N

N

N

O

H

NH

O O

O

O

OH

O

O

O O

491 Aurilide Type: Simple cyclic depsipeptides. C44H75N5O10 Powder, [α]D25 = −17° (c = 0.06, MeOH). Source: Sea hare Dolabella auricularia. Pharm: Cytotoxic (HeLa-S3, IC50 = 0.011 μg/mL). Ref: K. Suenaga, et al, Tetrahedron, 2004, 60, 8509

O N

N O HN

O

O O

N H

OH

O N O

O

O

492 Aurilide B Type: Simple cyclic depsipeptides. C44H75N5O10 Amorph. solid, [α]D24 = −17° (c = 0.34, MeOH). Source: Cyanobacterium Lyngbya majuscula (Papua New Guinea). Pharm: Anticancer-Cell-Effect (model: rat aorta A-10 cells, mechanism: microfilament disruption); cytotoxic (MTT assay, H460 and neuro-2a, LC50 = 0.01–0.13 μmol/L); cytotoxic (NCI 60 cell line panel, high level of cytotoxicity, mean panel GI50 < 10 nmol/L, particularly active against leukemia, renal, and prostate cancer cell lines). Ref: B. Han, et al, JNP, 2006, 69, 572│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev)

1.14 Simple Cyclic Depsipeptides

199

R

O

H

N

N O O

NH O

O

N

NH

S

OH

O

H

O

O

O

493 Aurilide C Type: Simple cyclic depsipeptides. C43H73N5O10 Amorph. solid, [α]D24 = −19° (c = 0.39, MeOH). Source: Cyanobacterium Lyngbya majuscula (Papua New Guinea). Pharm: Cytotoxic (MTT assay, H460 and neuro-2a, LC50 = 0.01–0.13 μmol/L). Ref: B. Han, et al, JNP, 2006, 69, 572 R

H N O O

O

O N

NH O N

NH

H

O

OH

O

O

O

494 Bacillistatin 1 Type: Simple cyclic depsipeptides. C57H96N6O18 Prisms (MeOH aq). Source: Marinederived bacterium Bacillus silvestris from Pacific Ocean crab (Quellon, Chiloé I., Chile). Pharm: Cytotoxic (P388, ED50 = 0.023 μg/mL, control Valinomycin, ED50 = 0.120 μg/mL; BXPC3, GI50 = 0.00095 μg/mL,Valinomycin, GI50 = 0.0019 μg/mL; MCF7, GI50 = 0.00061 μg/mL, Valinomycin, GI50 = 0.0010 μg/mL; SF268, GI50 = 0.00045 μg/mL, Valinomycin, GI50 = 0.0027 μg/mL; NCI-H460, GI50 = 0.00230 μg/mL, Valinomycin, GI50 = 0.0025 μg/mL; KM20L2, GI50 = 0.00087 μg/mL, Valinomycin, GI50 = 0.0008 μg/mL; DU145, GI50 = 0.00150 μg/mL, Valinomycin, GI50 = 0.0035 μg/mL); antibacterial (Streptococcus pneumoniae ATCC 6303, MIC = 2 μg/mL, MBC = 4 μg/mL; PRSP, MIC = 1 μg/mL, MBC = 2 μg/mL; MDRSP ATCC 700673, MIC < 0.5 μg/mL, MBC = 1 μg/mL; Streptococcus pyogenes, MIC = 4 μg/mL, MBC > 32 μg/mL). Ref: G. R. Pettit, et al, JNP, 2009, 72, 366

200

1 Peptides

O O

HN

O

H

O

O

S

O

N H

O O

O

H

HN

NH

O O O

O

H H N

O

O

O NH

O

O

495 Bacillistatin 2 Type: Simple cyclic depsipeptides. C57H96N6O18 Prisms (MeOH aq). Source: Marinederived bacterium Bacillus silvestris from Pacific Ocean crab (Quellon, Chiloé I., Chile). Pharm: Cytotoxic (P388, ED50 = 0.013 μg/mL, control Valinomycin, ED50 = 0.120 μg/mL; GI50 = 0.00034 μg/mL, Valinomycin, GI50 = 0.0019 μg/mL; MCF7, GI50 = 0.00031 μg/mL, Valinomycin, GI50 = 0.0010 μg/mL; SF268, GI50 = 0.00180 μg/mL, Valinomycin, GI50 = 0.0027 μg/mL; NCI-H460, GI50 = 0.00045 μg/mL, Valinomycin, GI50 = 0.0025 μg/mL; KM20L2, GI50 = 0.00026 μg/mL, Valinomycin, GI50 = 0.0008 μg/mL; DU145, GI50 = 0.00086 μg/mL, Valinomycin, GI50 = 0.0035 μg/mL); antibacterial (Streptococcus pneumoniae ATCC 6303, MIC = 1 μg/mL, MBC = 2 μg/mL; PRSP, MIC = 1 μg/mL, MBC = 1 μg/mL; MDRSP ATCC 700673, MIC < 0.5 μg/mL, MBC < 0.5 μg/mL; Streptococcus pyogenes, MIC = 2 μg/mL, MBC > 16 μg/mL). Ref: G. R. Pettit, et al, JNP, 2009, 72, 366; 372 O O

HN

O

H

O

O

N H

O

O O

O

HN

NH

O O O

O

H

H H N

O O

O

O NH

O

496 Bouillonamide Type: Simple cyclic depsipeptides. C46H67N5O8 Source: Cyanobacterium Moorea bouillonii (New Britain I., Papua New Guinea). Pharm: Cytotoxic (neuro-2a). Ref: L. T. Tan, et al, Mar. Drugs, 2013, 11, 3015

1.14 Simple Cyclic Depsipeptides

201

HO O N

N O

O

N

O

O

NH N

O

O

497 Bromoalterochromide A Type: Simple cyclic depsipeptides. C38H50BrN7O10 Yellow solid. Source: Marinederived bacterium Pseudoalteromonas maricaloris KMM 636. Pharm: Cytotoxic (developing eggs of sea urchin Strongylocentrotus intermedius). Ref: M. Speitling, et al, J. Antibiot., 2007, 60, 36

O

O H 2N O H 2N

O

NH N H

H N H

O

O

O H N O

O N H

Br 2

OH

498 Callipeltin A Type: Simple cyclic depsipeptides. C68H116N18O20 [α]D = +3.56° (c = 0.012, MeOH). Source: Sponges Callipelta sp. (New Caledonia)and Latrunculia sp. Pharm: Cytotoxic (number of tumor cell lines, including several drug-resistant cell lines); anti-HIV (protects cells infected by HIV virus); antifungal (Candida albicans, 100 μg/disc, IZD = 30 mm); positive inotropic effect. Ref: M. V. D’Auria, et al, Tetrahedron, 1996, 52, 9589│A. Zampella, et al, JACS, 1996, 118, 6202│L. Trevisi, et al, Biochem. Biophys. Res. Commun., 2000, 279, 219│A. Zampella, et al, Tet. Lett., 2002, 43, 6163│A. Zampella, et al, Org. Lett., 2005, 7, 3585│A. E. Wright, Current Opinion in Biotechnology 2010, 21, 801│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)

202

1 Peptides

NH2

HN

NH2

O

NH O

OH

NH

N H H

OH

H H N

NH

O

HN

O O

N

O

O

H HO O

NH2

HN

O

OH

HN

H O N H

O

O

OH

O

NH

O N

N H

O NH2

499 Callipeltin B Type: Simple cyclic depsipeptides. C47H74N12O14 [α]D = +11.3° (MeOH). Source: Sponges Callipelta sp. (off New Caledonia) and Latrunculia sp. Pharm: Cytotoxic (KB, P388, NSCLC-N6, cell proliferation inhibitor). Ref: M. V. D’Auria, et al, Tetrahedron, 1996, 52, 9589│A. Zampella, et al, Tet. Lett., 2002, 43, 6163│S. Calimsiz, et al, JOC, 2006, 71, 6351│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)

O

N H

O

O

OH

O

H H N

H N H

O

O

N H

O

O N O

NH

HN NH2

O

N

N H

O

H

NH2

NH

O

OH

500 Celebeside A Type: Simple cyclic depsipeptides. C37H62N7O16P Amorph. powder, [α]D23 = −49.9° (c = 0.32, MeOH). Source: Lithistid sponge Siliquariaspongia mirabilis (off Sulawesi I., Indonesia). Pharm: Cytotoxic (HCT116, IC50 = 9.9 μmol/L); cytotoxic (HCT116, IC50 = (8.8 ± 3.0)μg/mL); anti-HIV-1 (HIV-1 SF162 envelope, neutralized HIV-1 in singleround infectivity assay, IC50 = (1.9 ± 0.4)μg/mL). Ref: A. Plaza, et al, JOC, 2009, 74, 504│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)

1.14 Simple Cyclic Depsipeptides

O

OH

NH2

O

O

HO

O

HN

NH2

OH

OH

O

N H O

O

P O

O

H N

HN

203

N O

O

O

501 Celebeside C Type: Simple cyclic depsipeptides. C37H61N7O13 Amorph. powder, [α]D23 = −3.4° (c = 0.06, MeOH). Source: Lithistid sponge Siliquariaspongia mirabilis (off Sulawesi I., Indonesia). Pharm: Cytotoxic (HCT116, IC50 > 31 μmol/L). Ref: A. Plaza, et al, JOC, 2009, 74, 504│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev) NH2

O O

H N

HN HO

HN

O

OH

O

O

N H O

O

OH

NH2

N

O

O

O

502 Cereulide Type: Simple cyclic depsipeptides. C57H96N6O18 Powder, [α]D = +10.4° (MeOH). Source: Marine-derived bacterium Bacillus cereus SCRC-4h1-2 from prosobranch Littorina sp. (surface). Pharm: Cytotoxic (P388, IC50 = 0.0082 ng/mL, Colon26, IC50 = 0.035 ng/mL); Rb and K selective ionophore; emetic toxin. Ref: G. -Y. -S. Wang, et al, Chem. Lett., 1995, 791

204

1 Peptides

O O

H N

O

O

NH O

O O O

HN

O O

O

HN

O

O

O

O

H N

O

NH

O

O

503 Chondramide A Type: Simple cyclic depsipeptides. C36H46N4O7 Glass, [α]D = +2.1° (c = 2, MeOH). Source: Myxobacterium Chondromyces crocatus Cmc5. Pharm: Cytotoxic. Ref: B. Kunze, et al, J. Antibiot., 1995, 48, 1262│R. Jansen, et al, Annalen, 1996, 285

O O

O

O N H

O

NH N O

N H OH

504 Coibamide A Type: Simple cyclic depsipeptides. C65H110N10O16 Oil, [α]D23 = −54.1° (c = 0.02, CHCl3). Source: Cyanobacterium Leptolyngbya sp. (Coiba National Park, Panama). Pharm: Anticancer-Cell-Effect (model: NCI-H460, mechanism: cell cycle inhibition); cytotoxic (MTT assay, NCI-H460, MDA-MB-231, LOX-IMVI, HL60 and SNB75); cytotoxic (NCI 60 cancer cell line panel, unprecedented selectivity profile, antiproliferative). Ref: R. A. Medina, et al, JACS, 2008, 130, 6324

1.14 Simple Cyclic Depsipeptides

O

205

H N N N

O O O

N O O

O

O

O

O

O

O

N

N

N

N

O

O

H N

NH O

O

505 Cryptophycin 1 Cryptophycin A Type: Simple cyclic depsipeptides. C35H43ClN2O8 [α]D25 = +33.8° (c = 1.8, MeOH). Source: Cyanobacteria Nostoc sp. GSV 224 and Nostoc spp. Pharm: Cytotoxic (KB, IC50 = 5 pg/mL; LoVo, IC50 = 3 pg/mL; highly potent suppressor of microtubule dynamics and blocks cells in G2/M phase; 100–1000 times more potent than currently available anticancer drugs such as taxol or vinblastine) (Patterson, 1991); cytotoxic (M17; DMS273) (Patterson, 1991); cytotoxic (KB, IC50 = 0.0092 nmol/L; LoVo, IC50 = 0.010 nmol/L; SK-OV-3, IC50 = 0.020 nmol/L) (Golatoki, 1995); anticancerCell-Effect (model: MDA-MB-435, mechanism: caspase-3 protein activation); anticancer-Cell-Effect (model: MDA-MB-435 and SK-OV-3, mechanism: cell cycle inhibition). Ref: G. M. L. Patterson, et al, J. Phycol. 1991, 27, 530│T. Golatoki, et al, JACS, 1995, 117, 12030│CRC Press, DNP on DVD, 2012, version 20.2│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev) 8

O

O 7

O

O

H

HN

O

Cl 2'

6'

2''

N H

O

O

O

506 Cryptophycin 16 Type: Simple cyclic depsipeptides. C34H41ClN2O8 [α]D = +41.3° (c = 5.2, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 0.359 nmol/L; LoVo, IC50 = 0.273 nmol/L; SK-OV-3, IC50 = 0.606 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030│CRC Press, DNP on DVD, 2012, version 20.2 8

O

O 7

O

O

H

HN

O

Cl 2'

6'

2''

O

N H

O

OH

206

1 Peptides

507 Cryptophycin 17 Type: Simple cyclic depsipeptides. C34H41ClN2O7 [α]D = +27.8° (c = 0.37, CHCl3). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 7.53 nmol/L; LoVo, IC50 = 9.46 nmol/L; SK-OV-3, IC50 = 17.7 nmol/L). Ref: G. Trimurtulu, et al, JACS, 1994, 116, 4729│T. Golatoki, et al, JACS, 1995, 117, 12030

7

O

8

O

O

H

HN

O

6'

Cl

2' 2''

N H

O

O

OH

508 Cryptophycin 175 Type: Simple cyclic depsipeptides. C35H42Cl2N2O7 [α]D = +32.8° (c = 0.81, CHCl3). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, LoVo, SK-OV-3, IC50 ≈ 100 nmol/L). Ref: G. V. Subbaraju, et al, JNP, 1997, 60, 302 7

O

8

O

O

H

HN

O

Cl 2'

6'

2''

N H

O

O

O

Cl

509 Cryptophycin 176 Type: Simple cyclic depsipeptides. C33H39ClN2O8 [α]D = +40.5° (c = 0.38, MeOH). Source: Cyanobacterium Nostoc sp. ATCC 53789. Pharm: Cytotoxic (KB, LoVo, SK-OV-3, IC50 = 1.3–1.6 nmol/L). Ref: G. V. Subbaraju, et al, JNP, 1997, 60, 302 8R

O

3

7R

O

O

O HN

O

Cl 2'

6'

2''

O

N H

O

OH

510 Cryptophycin 18 Type: Simple cyclic depsipeptides. C35H43ClN2O7 [α]D = +54.9° (c = 0.93, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 48.6 nmol/L; LoVo, IC50 = 20.4 nmol/L; SK-OV-3, IC50 = 36.6 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030

1.14 Simple Cyclic Depsipeptides

7

O

8

O

207

O

H

HN

O

6'

Cl

2' 2''

N H

O

O

O

511 Cryptophycin 19 Type: Simple cyclic depsipeptides. C34H41ClN2O7 [α]D = +62.6° (c = 0.67, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 11.7 nmol/L; LoVo, IC50 = 11.2 nmol/L; SK-OV-3, IC50 = 65.1 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030

7

O

8

O

O

H

HN

O

6'

Cl

2' 2''

N H

O

O

O

512 Cryptophycin 2 Cryptophycin B Type: Simple cyclic depsipeptides. C35H44N2O8 [α]D25 = +20.4° (c = 0.5, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 0.073 nmol/L; LoVo, IC50 = 0.110 nmol/L; SK-OV-3, IC50 = 0.057 nmol/L). Ref: G. Trimurtulu, et al, JACS, 1994, 116, 4729│T. Golatoki, et al, JACS, 1995, 117, 12030 8R

O

O 7R

O

O

H

HN

O

6'

2' 2''

O

N H

O

O

513 Cryptophycin 21 Type: Simple cyclic depsipeptides. C34H41ClN2O8 [α]D = +40.2° (c = 0.72, CHCl3). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 0.017 nmol/L; LoVo, IC50 = 0.019 nmol/L; SK-OV-3, IC50 = 0.050 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030

208

1 Peptides

8

O

3

7

O

O

O HN

O

Cl 2'

6'

2''

N H

O

O

O

514 Cryptophycin 23 Type: Simple cyclic depsipeptides. C34H40Cl2N2O8 [α]D = +47° (c = 1.55, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 3.12 nmol/L; LoVo, IC50 = 0.59 nmol/L; SK-OV-3, IC50 = 2.52 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030 8

O

7

O

O

O

H

HN

O

Cl 2'

6'

2''

N H

O

O

OH Cl

515 Cryptophycin 24 Arenastatin A Type: Simple cyclic depsipeptides. C34H42N2O8 Amorph. solid, [α]D = +19° (c = 0.1, MeOH), [α]D = +48.8° (c = 0.63, CHCl3). Source: Cyanobacterium Nostoc sp. ATCC 53789., sponge Dysidea arenaria. Pharm: Cytotoxic (KB, IC50 = 0.198 nmol/L; LoVo, IC50 = 0.157 nmol/L; SK-OV-3, IC50 = 0.499 nmol/L); cytotoxic (KB, IC50 = 5 pg/mL); antimitotic; microtubule assembly inhibitor; antifungal (selective). Ref: M. Kobayashi, et al, CPB, 1993, 41, 989; 1994, 42, 2196; 1994, 42, 2394; 1995, 43, 1598│M. Kobayashi, et al, Tet. Lett., 1994, 35, 7969│T. Golatoki, et al, JACS, 1995, 117, 12030│Y. Koiso, et al, Chem. Biol. Interact., 1996, 102, 183│J. D. White, et al, Tet. Lett., 1998, 39, 8779│J. D. White, et al, JOC, 1999, 64, 6206 8

O

O

7

O

O

HN

O

HN

O

O

O

516 Cryptophycin 26 Type: Simple cyclic depsipeptides. C35H45ClN2O8 [α]D = +28.2° (c = 1.31, CHCl3). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 35.1 nmol/L; LoVo, IC50 = 18.3 nmol/L; SK-OV-3, IC50 = 142 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030

1.14 Simple Cyclic Depsipeptides

209

O OH O

O

HN

O

HN

Cl O

O

O

517 Cryptophycin 28 Type: Simple cyclic depsipeptides. C34H41ClN2O7 [α]D = +65.6° (c = 0.93, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 2.88 nmol/L; LoVo, IC50 = 1.11 nmol/L; SK-OV-3, IC50 = 9.76 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030 7

3

O

8

O

O

HN

O

Cl 2'

6'

2''

N H

O

O

O

518 Cryptophycin 29 Type: Simple cyclic depsipeptides. C34H41ClN2O7 [α]D = +22.2° (c = 1.13, CHCl3). Source: Cyanobacterium Nostoc sp. ATCC 53789. Pharm: Cytotoxic (KB, IC50 = 3.69 nmol/L; LoVo, IC50 = 1.04 nmol/L; SK-OV-3, IC50 = 5.9 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030

7

3

O

8

O

O

HN

O

Cl 2'

6'

2''

O

N H

O

O

519 Cryptophycin 3 Cryptophycin C Type: Simple cyclic depsipeptides. C35H43ClN2O7 [α]D25 = +20.3° (c = 1.1, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 3.13 nmol/L; LoVo, IC50 = 1.88 nmol/L; SK-OV-3, IC50 = 4.36 nmol/L). Ref: G. Trimurtulu, et al, JACS, 1994, 116, 4729│T. Golatoki, et al, JACS, 1995, 117, 12030

210

1 Peptides

7

O

8

O

O

H

HN

O

Cl

6' 2'

2''

N H

O

O

O

520 Cryptophycin 30 Type: Simple cyclic depsipeptides. C35H45ClN2O8 [α]D = −12.3° (c = 1.53, CHCl3). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 18.3 nmol/L; LoVo, IC50 = 10.8 nmol/L; SK-OV-3, IC50 = 31.6 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030 7

3

O

8

O

O

H O

OH HN

Cl 2'

6'

2''

N H

O

O

O

521 Cryptophycin 31 Type: Simple cyclic depsipeptides. C35H42Cl2N2O8 [α]D = +50.6° (c = 1.13, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 2.62 nmol/L; LoVo, IC50 = 0.218 nmol/L; SK-OV-3, IC50 = 1.23 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030 8

O

O

7

O

O

H

HN

O

Cl 2'

6'

2''

N H

O

O

O

Cl

522 Cryptophycin 4 Cryptophycin D Type: Simple cyclic depsipeptides. C35H44N2O7 [α]D25 = +36.7° (c = 1.9, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 16.5 nmol/L; LoVo, IC50 = 21.5 nmol/L; SK-OV-3, IC50 = 34.5 nmol/L). Ref: G. Trimurtulu, et al, JACS, 1994, 116, 4729│T. Golatoki, et al, JACS, 1995, 117, 12030 7

O

8

O

O

H

HN

O

6'

2' 2''

O

N H

O

O

1.14 Simple Cyclic Depsipeptides

211

523 Cryptophycin 40 Type: Simple cyclic depsipeptides. C34H41ClN2O8 [α]D = +41.6° (c = 0.31, CHCl3). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 0.61 nmol/L; LoVo, IC50 = 0.625 nmol/L; SK-OV-3, IC50 = 2.63 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030 8

O

3

7

O

O

O HN

O

Cl 2'

6'

2''

N H

O

O

O

524 Cryptophycin 43 Type: Simple cyclic depsipeptides. C34H42N2O7 [α]D = +20° (c = 0.2, CHCl3). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 1.22 nmol/L; LoVo, IC50 = 1.36 nmol/L; SK-OV-3, IC50 = 1.88 nmol/L). Ref: G. Trimurtulu, et al, JACS, 1994, 116, 4729│T. Golatoki, et al, JACS, 1995, 117, 12030

7

O

8

O

O

H

HN

O

6'

2' 2''

N H

O

O

OH

525 Cryptophycin 45 Type: Simple cyclic depsipeptides. C34H40Cl2N2O7 [α]D = +72° (c = 0.2, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 3.5 nmol/L; LoVo, IC50 = 3.6 nmol/L; SK-OV-3, IC50 = 2.48 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030

7

O

8

O

O

H

HN

O

Cl 2'

6'

2''

O

N H

O

OH Cl

526 Cryptophycin 46 Type: Simple cyclic depsipeptides. C35H43ClN2O7 [α]D = −62.1° (c = 0.66, CHCl3). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, LoVo, SK-OV-3, IC50 = 750–1100 nmol/L). Ref: G. V. Subbaraju, et al, JNP, 1997, 60, 302

212

1 Peptides

7

O

8

O

O

H

HN

O

Cl 2'

6'

2''

N H

O

O

O

527 Cryptophycin 49 Type: Simple cyclic depsipeptides. C34H41ClN2O7 [α]D = +68.1° (c = 0.07, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 2.24 nmol/L; LoVo, IC50 = 3.04 nmol/L; SK-OV-3, IC50 = 1.82 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030

7

O

8

O

O

H

HN

O

6'

Cl

2' 2''

N H

O

O

O

528 Cryptophycin 50 Type: Simple cyclic depsipeptides. C34H41ClN2O8 [α]D = +32° (c = 0.44, CHCl3). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 0.047 nmol/L; LoVo, IC50 = 0.094 nmol/L; SK-OV-3, IC50 = 0.607 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030 8

O

7

O

O O

H

HN

O

6'

Cl

2' 2''

O

N H

O

O

529 Cryptophycin 52 Type: Simple cyclic depsipeptides. C36H45ClN2O8 Solid, [α]D = +19.9° (c = 0.5, CHCl3). Source: Synthetic. Pharm: Antimitotic, antineoplastic (entered a clinical trial but produced only marginal activity, two other analogues cryptophicins with improved stability and water solubility are being considered as second-generation clinical candidates). Ref: C. Shin, et al, Curr. Pharmaceutical Design, 2001, 13, 1259│J. Liang, et al, InVest. New Drugs, 2005, 23, 213

1.14 Simple Cyclic Depsipeptides

8

213

O

O

7

O

O

H

HN

O

Cl 2'

6'

2''

N H

O

O

O

530 Cryptophycin 54 Type: Simple cyclic depsipeptides. C35H43ClN2O8 [α]D = +20.7° (c = 0.73, MeOH). Source: Cyanobacterium Nostoc sp. GSV 224. Pharm: Cytotoxic (KB, IC50 = 1.22 nmol/L; LoVo, IC50 = 3.36 nmol/L; SK-OV-3, IC50 = 3.33 nmol/L). Ref: T. Golatoki, et al, JACS, 1995, 117, 12030 8 7

O

O

O O

H

HN

O

6'

Cl

2' 2''

N H

O

O

O

531 33-Demethoxy-33-(methylsulfinyl)theonellapeptolide Id Type: Simple cyclic depsipeptides. C70H125N13O16S Amorph. solid, [α]D25 = −45° (c = 1.0, MeOH). Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Antibacterial (gram-positive bacteria Staphylococcus aureus, Micrococcus luteus, Bacillus subtilis, Mycobacterium smegmatis, MIC = 8.0 μg/mL, 8.0 μg/mL, 8.0 μg/mL, 16 μg/mL respectively); antifungal (Trichophyton mentagrophytes, Aspergillus niger, MIC = 4.0 μg/mL, MIC > 66 μg/mL, respectively); cytotoxic (L1210, IC50 = 9.0 μg/mL). Ref: M. Tsuda, et al, Tetrahedron, 1999, 55, 10305

O

S

H N O

O

O H N

N MLeu O

W=beta-Ala

O

Thr

N H

N H

N Leu X=MeIle

O

O

O

NH beta-Ala

O Z=MeIle

N

O

O

HN

Leu

O

NH H N

O

N

beta-Ala

O

10MeAla

Y=Ile

O N MeVal

214

1 Peptides

532 33-Demethoxytheonellapeptolide Ie Type: Simple cyclic depsipeptides. C70H125N13O15 Amorph. solid, [α]D24 = −56° (c = 1.0, MeOH). Source: Lithistid sponge Theonella sp. (Okinawa). Pharm: Antibacterial (gram-positive bacteria Staphylococcus aureus, Micrococcus luteus, Bacillus subtilis, Mycobacterium smegmatis, MIC ≥ 16 μg/mL, 8.0 μg/mL, 16 μg/mL, 66 μg/mL respectively); antifungal (Trichophyton mentagrophytes, Aspergillus niger, MIC = 8.0 μg/mL); cytotoxic (L1210, IC50 = 7.5 μg/mL). Ref: M. Tsuda, et al, Tetrahedron, 1999, 55, 10305

33

O

O

HN

H N

N MLeu O

O

O Thr

N W=beta-MeAla

N H

N Leu

O

O

X=MeIle

O

NH beta-Ala

O Z=MeIle

N

O Leu

O

NH H N

O

O

HN

N

N

MeVal

beta-Ala

O

Y=Ile

O

10MeAla

533 22ʹ-Deoxythiocoraline Type: Simple cyclic depsipeptides. C48H56N10O11S6 White solid, [α]D25 = −98° (c = 0.0005, CHCl3). Source: Marine-derived bacterium Verrucosispora sp. from lithistid sponge Chondrilla caribensis f. caribensis (Florida Keys, USA). Pharm: Cytotoxic (A549, EC50 = 0.13 μmol/L). Ref: T. P. Wyche, et al, JOC, 2011, 76, 6542 OH

O H N

N O

O

S

S NH O

S

N O

O

N

N S

N

O HN S

S O

O N H

O N

1.14 Simple Cyclic Depsipeptides

215

534 Depsipeptide 1962A Type: Simple cyclic depsipeptides. C30H45N5O8 Cryst., mp 180–182 °C, [α]D20 = −63.4° (c = 0.005, MeOH). Source: An unidentified mangrove-derived fungus 1962 from mangrove Kandelia candel (Hong Kong). Pharm: Cytotoxic (MCF7, mild). Ref: H. Huang, et al, JNP, 2007, 70, 1696

O

H N

O

HO

O

N H

4''

NH O

O

H N

N H

O

O

535 Desmethoxymajusculamide C Type: Simple cyclic depsipeptides. C49H78N8O11 Oil, [α]D22 = −104° (c = 1.86, CH2Cl2). Source: Cyanobacterium Lyngbya majuscula. Pharm: Cytotoxic (HCT116, IC50 = 0.020 μmol/L; H460, IC50 = 0.063 μmol/L; MDA-MB-435, IC50 = 0.22 μmol/L; neuro2a, IC50 > 1.0 μmol/L); antineoplastic (therapeutic studies, HCT116 bearing SCID mice demonstrated efficacy at highest dose used (T/C = 60% at 0.62 mg/kg daily for 5 days)). Ref: T. L. Simmons, et al, JNP, 2009, 72, 1011 O

H N

N H

N

O O N

O

O N H

O H H N

O

O

O N

O

H

H N

O

57

536 Desmethylisaridin C1 Type: Simple cyclic depsipeptides. C35H53N5O7 Source: Marine-derived fungus Beauveria felina EN-135. Pharm: Antibacterial (Escherichia coli, MIC = 8 μg/mL). Ref: F. Y. Du, et al, JNP, 2014, 77, 1164

216

1 Peptides

O

O

N

H N

O O

O N N H

N H

O

O

537 Desmethylisaridin G Type: Simple cyclic depsipeptides. C35H53N5O8 Source: Marine-derived fungus Beauveria felina EN-135. Pharm: Antibacterial (Escherichia coli, MIC = 64 μg/mL). Ref: F. Y. Du, et al, JNP, 2014, 77, 1164 OH O

O

N

H N

O O

O N N H O

N H

O

538 Didemnin A Type: Simple cyclic depsipeptides. C49H78N6O12 [α]D = −149.1° (CHCl3). Source: Ascidians Trididemnum solidum (Little San Salvador I., Bahamas) and Trididemnum sp. Pharm: Antiviral (inhibits growth of RNA and DNA viruses: coxsackie virus and equine rhinovirus (both RNA viruses) and Herpes simplex 2 (DNA virus), ID50 = 1.5 μg/mL; HSV-1, ID50 = 3 μg/mL); immunosuppressive (MLR assay, IC50 = 0.98 nmol/L); cytotoxic (P388, IC50 = 11 nmol/L); cytotoxic (HCT116, IC50 = 32 nmol/L). Ref: K. L. Rinehart, Jr., et al, Science, 1981, 212, 933│K. L. Rinehart, et al, JACS, 1981, 103, 1857; 1987, 109, 6846│B. Liang, et al, JACS, 2001, 123, 4469│T. F. Molinski, et al, JNP, 2011, 74, 882

1.14 Simple Cyclic Depsipeptides

217

O

H

N

N

O O O

O

H

N H H

O HN

N H

O

H

NH

O O

OH

O

O

539 epi-Didemnin A1 Type: Simple cyclic depsipeptides. C49H78N6O12 Powder, mp 130–132 °C, [α]D23 = −100° (c = 0.1, CHCl3). Source: Ascidian Trididemnum solidum (Carrbbean). Pharm: Cytotoxic (P388, IC50 = 2.0 μg/mL). Ref: W. R. Li, et al, Stud. Nat. Prod. Chem., 1992, 10, 241│R. Sakai, et al, JACS, 1995, 117, 8885│M. D. Vera, et al, Med. Res. Rev., 2002, 22, 102 O O N

N

O

O O

O

NH O 13

O

O

HO

O NH

O N H

NH R=H

540 Didemnin B Type: Simple cyclic depsipeptides. C57H89N7O15 [α]D = –91.9° (CHCl3). Source: Ascidians Trididemnum solidum and Trididemnum cyanophorum (family Didemnidae). Pharm: Immunosuppressive (MLR assay, IC50 = 0.42 nmol/L); antiviral (inhibits growth of RNA and DNA viruses); cytotoxic (P388, IC50 = 1.8 nmol/L); cytotoxic (HCT116, IC50 = 9.0 nmol/L); antineoplastic. (L1210, ID50 = 0.0011 μg/mL, P388, T/C = 199%; B16, T/C = 160%). Ref: K. L. Rinehart, et al, JACS, 1981, 103, 1857│K. L. Rinehart, et al, Science (Washington, D.C.), 1981, 212, 933│B. Liang, et al, JACS, 2001, 123, 4469│T. F. Molinski, et al, JNP, 2011, 74, 882

218

1 Peptides

H

O

O

O O

NH N

N

N

N O

H

N H H

H

O

NH

O O

OH

O

O

O

O

O

541 Didemnin C Type: Simple cyclic depsipeptides. C52H82N6O14 [α]D = −118.9° (CHCl3). Source: Ascidians Trididemnum sp. (Caribbean Sea) and Trididemnum spp. Pharm: Antiviral (inhibits growth of both RNA and DNA viruses); cytotoxic (L1210, P388 and B16, high active). Ref: K. L. Rinehart, Jr., et al, Science, 1981, 212, 933│K. L. Rinehart, Jr., et al, JACS, 1981, 103, 1857 OH

O O

OH

O N

O

O N H

O O HN

NH O

O O O N

N

O

542 Didemnin M Didemnin H Type: Simple cyclic depsipeptides. C67H102N10O19 Powder, mp 158–160 °C, [α]D25 = −68.4° (c = 1.1, CHCl3). Source: Ascidian Trididemnum cyanophorum. Pharm: Immunosuppressive (MLR assay, IC50 = 0.00076 nmol/L); cytotoxic (P388, IC50 = 1.5 nmol/L). Ref: A. Boulanger, et al, Tet. Lett., 1994, 35, 4345│R. Sakai, et al, JACS, 1995, 117, 3734; 8885│B. Liang, et al, JACS, 2001, 123, 4469

1.14 Simple Cyclic Depsipeptides

219

O O

N O

O

N O

NH

O

O

O

O OH

NH NH O

O NH2

O

O

N

O O O

N N H

H N

O

O

543 Didemnin N Type: Simple cyclic depsipeptides. C55H85N7O15 Amorph. solid, mp 150–152 °C, [α]D24 = −49° (c = 1.6, CHCl3). Source: Ascidians Trididemnum solidum (Carrbbean) and Trididemnum cyanophorum (Guadeloupe I.). Pharm: Cytotoxic (P388, IC50 = 5.0 μg/mL). Ref: R. Sakai, et al, JACS, 1995, 117, 8885│E. Abou-Mansour, et al, Tetrahedron, 1995, 51, 12 591

O N O O

O

N H O

NH O

O

O OH

NH NH O

O

O

N

O N HO

544 Dolastatin 11 Type: Simple cyclic depsipeptides. C50H80N8O12 Powder, mp 134–137 °C, [α]D26 = −143.9° (c = 0.33, CH2Cl2). Source: Cyanobacteria Lyngbya majuscula and Schizothrix calcicola (assemblage), sea hare Dolabella auricularia (Indian Ocean). Pharm: Cytotoxic (P388, ED50 = 2.7 × 10-3 μg/mL). Ref: D. C. Carter, et al, JOC, 1984, 49, 236│G. R. Peddit, et al, Heterocycles, 1989, 28, 553│R. B. Bates, et al, JACS, 1997, 119, 2111

220

1 Peptides

31

O

H N

O H N

N H

11

15

O

O

O H

O

O N

O

O N

O

HN N

N H

O

O

545 Dolastatin 12 Type: Simple cyclic depsipeptides. C50H80N8O11 Powder, mp 130–135 °C, [α]D24 = −98° (c = 0.01, MeOH). Source: Cyanobacteria Lyngbya majuscula and Schizothrix calcicola (assemblage), cyanobacterium Leptolyngbya sp., sea hare Dolabella auricularia (Indian Ocean). Pharm: Anticancer-Cell-Effect (model: rat aorta A-10 cells, mechanism: microfilament disruptor) (Harrigan, 1998); cytotoxic (MTT assay, hmn A549); antineoplastic (PS, ED50 = 7.5 × 10-2 μg/mL). Ref: G. R. Peddit, et al, Heterocycles, 1989, 28, 553│G. G. Harrigan, JNP, 1998, 61, 1221│A. Catassi, et al, Cell. Mol. Life Sci., 2006, 63, 2377│CRC Press, DNP on DVD, 2012, version 20.2 31

O O

N 15

O

N H

11

H N

O

O

H

O

O N O

O N O

N H

HN N O

546 Dolastatin 16 Type: Simple cyclic depsipeptides. C47H70N6O4 Colorless amorphous solid, [α]D20 = +22° (c = 0.18, MeOH); amorph. powder, [α]D20 = +15.5° (c = 0.2, MeOH). Source: Cyanobacterium Symploca cf. hydnoides (Cetti Bay, Guam), sea hare Dolabella auricularia (Papua New Guinea). Pharm: Cytotoxic (MTT assay, MCF7, Log10 GI50 (mol/L) = −7.32; MDA-MB-435, Log10 GI50 (mol/L) = −7.46; MDA-N, Log10 GI50 (mol/L) = −7.54); cytotoxic (NCI-H460, GI50 = 0.00096 μg/mL; KM20L2, GI50 = 0.0012 μg/mL; SF295, GI50 = 0.0052 μg/mL; SK-MEL-5, GI50 = 0.0033 μg/mL); cytotoxic (panel of 60 hmn cancer cell lines, mean panel GI50 = 2.5 × 10-7 mol/L, relatively GI50-COMPARE correlation = 0.76 and 0.71 with dolastatins 10 and 15 respectively); cytotoxic (HT29, IC50 = 78 μmol/L, control Paclitaxel, IC50 = 0.003 μmol/L; HeLa, IC50 = 58 μmol/L, Paclitaxel, IC50 = 0.0026 μmol/L). Ref:

1.14 Simple Cyclic Depsipeptides

221

G. R. Pettit, et al, JNP, 1997, 60, 752│G. R. Pettit, et al Bioorg. Med. Chem, Lett., 1997, 7, 827│L. A. Salvador, et al, JNP, 2011, 74, 917 O

H

O

N

N

N O

O

O HN O

O

O

H

N

H N

O

O

547 Dolastatin 17 Type: Simple cyclic depsipeptides. C41H67N5O9 Amorph. powder, [α]D = −145° (c = 0.1, MeOH). Source: Sea hare Dolabella auricularia (Papua New Guinea). Pharm: Cytotoxic. Ref: G. R. Pettit, et al, Heterocycles, 1998, 47, 491 O N

O O

N

O

O

O

NH

O

N O

NH O

548 Dolastatin D Type: Simple cyclic depsipeptides. C31H47N3O7 Needles (hexane/CH2Cl2), mp 200–201 °C, [α]D25 = −73° (c = 0.13, MeOH). Source: Sea hare Dolabella auricularia. Pharm: Cytotoxic (HeLa-S3, IC50 = 2.2 μg/mL). Ref: H. Sone, et al, Tet. Lett., 1993, 34, 8449│H. Sone, et al, Tet. Lett., 1993, 34, 8445

O

N O O O

O

O H N

NH

O

222

1 Peptides

549 Dolastatin G Type: Simple cyclic depsipeptides. C57H96N6O13 Prisms (hexane/C6H6), mp 138–139 °C, [α]D25 = −211° (c = 0.4, MeOH). Source: Cyanobacterium Lyngbya majuscula (Guam). Pharm: Cytotoxic (HeLa-S3, IC50 = 1.0 μg/mL). Ref: T. Mutou, et al, JOC, 1996, 61, 6340 O O

N

N N

O

O

N

O

O O

H

N

55

O N

O

O

OH

O

37

O

550 Doliculide Type: Simple cyclic depsipeptides. C27H41IN2O6 Colorless fine needles, mp 173–174 °C, [α]D23 = −25.5° (c = 0.670, MeOH). Source: Sea hare Dolabella auricularia (Japan waters). Pharm: Cytotoxic (HeLa-S3, IC50 = 0.001 μg/mL). Ref: H. Ishiwata, et al, JOC, 1994, 59, 4710│H. Ishiwata, et al, JOC, 1994, 59, 4712│H. Ishiwata, et al, Tetrahedron, 1994, 50, 12853 O I

HO

OH O

N

O

O

N H

551 Emericellamide A Type: Simple cyclic depsipeptides. C31H55N5O7 Powder, [α]D24 = −50.2° (c = 0.1, MeOH). Source: Marine-derived fungus Emericella sp. CNL-878 (in co-culture with marine actinomycete Salinispora arenicola). Pharm: Antibacterial (MRSA, modest). Ref: D. C. Oh, et al, JNP, 2007, 70, 515

1.14 Simple Cyclic Depsipeptides

O

H N

N H O

O

O

NH

223

O

H N

O N H

O

552 Emericellamide B Type: Simple cyclic depsipeptides. C32H57N5O7 Powder, [α]D24 = −34° (c = 0.1, MeOH). Source: Marine-derived fungus Emericella sp. CNL-878 (in co-culture with marine actinomycete Salinispora arenicola). Pharm: Antibacterial (MRSA, modest). Ref: D. C. Oh, et al, JNP, 2007, 70, 515 O

H N

N H O

O

O

NH

O

H N

O N H

O

553 Exumolide A Type: Simple cyclic depsipeptides. C41H55N5O7 Solid, [α]D = −278° (c = 1.3, CHCl3). Source: Marine-derived fungus Scytalidium sp. (from decaying plant material, Exuma Is., 3m, Bahamas). Pharm: Antibiotic (green alga Dunaliella sp.); antimicroalgal. Ref: K. M. Jenkins, et al, Tet. Lett., 1998, 39, 2463

O N

O N Ph

O

O

N H Ph

O

O H N

N

O

554 Exumolide B Type: Simple cyclic depsipeptides. C40H53N5O7 Solid, [α]D = −288° (c = 2.1, CHCl3). Source: Marine-derived fungus Scytalidium sp. (from decaying plant material, Exuma Is., 3 m, Bahamas). Pharm: Antibiotic (green alga Dunaliella sp.); antimicroalgal. Ref: K. M. Jenkins, et al, Tet. Lett., 1998, 39, 2463

224

1 Peptides

O N

O N Ph

O

O

O

N H

O H N

NH

O

Ph

555 Geodiamolide A Type: Simple cyclic depsipeptides. C28H40IN3O6 Prisms (MeCN/CH2Cl2), mp 217–218 °C, [α]D25 = +53° (c = 0.04, CHCl3). Source: Sponges Geodia sp. (depth of 25 m, Rusts Bay, Trinidad and Tobago, West Indies) and Cymbastela sp. Pharm: Cytotoxic (L1210, ED50 = 0.0032 μg/mL). Ref: W. R. Chan,et al, JOC, 1987, 52, 3091│E. Dilip de Silva, et al, Tet. Lett., 1990, 31, 489│T. Imaeda, et al, Tet. Lett., 1994, 35, 591│Y. Hirai, et al, Heterocycles, 1994, 39, 603│T. Shioiri, et al, Heterocycles, 1997, 46, 421 O

HN I

HO

O O

N

O O

N H

556 Geodiamolide B Type: Simple cyclic depsipeptides. C28H40BrN3O6 Cryst. (MeCN/CH2Cl2), mp 203–204 °C, [α]D22 = +101° (c = 0.04, CHCl3). Source: Sponges Geodia sp. (depth of 25 m, Rusts Bay, Trinidad and Tobago, West Indies) and Cymbastela sp. Pharm: Cytotoxic (L1210, ED50 = 0.0026 μg/mL). Ref: W. R. Chan,et al, JOC, 1987, 52, 3091│E. Dilip de Silva,et al, Tet. Lett., 1990, 31, 489 O

HN Br

HO

O N

O

O O

N H

557 Geodiamolide C Type: Simple cyclic depsipeptides. C28H40ClN3O6 Source: Sponges Pseudaxinyssa sp. and Cymbastela sp. Pharm: Cytotoxic (L1210, ED50 = 0.0025 μg/mL). Ref: E. Dilip

1.14 Simple Cyclic Depsipeptides

225

de Silva, et al, Tet. Lett., 1990, 31, 489│C. Tanaka, et al, Tetrahedron, 2006, 62, 3536

O

HN Cl

HO

O O

N

O O

N H

558 Geodiamolide D Type: Simple cyclic depsipeptides. C27H38IN3O6 Source: Sponges Pseudaxinyssa sp. and Cymbastela sp. Pharm: Cytotoxic (L1210, ED50 = 0.0039 μg/mL). Ref: E. Dilip de Silva, et al, Tet. Lett., 1990, 31, 489

O

HN I HO

O O

N

O O

N H

559 Geodiamolide E Type: Simple cyclic depsipeptides. C27H38BrN3O6 Source: Sponges Pseudaxinyssa sp. and Cymbastela sp. Pharm: Cytotoxic (L1210, ED50 = 0.0014 μg/mL). Ref: E. Dilip de Silva, et al, Tet. Lett., 1990, 31, 489

O

HN Br HO

O N

O

O O

N H

560 Geodiamolide F Type: Simple cyclic depsipeptides. C27H38ClN3O6 Source: Sponges Pseudaxinyssa sp. and Cymbastela sp. Pharm: Cytotoxic (L1210, ED50 = 0.0006 μg/mL). Ref: E. Dilip de Silva, et al, Tet. Lett., 1990, 31, 489

226

1 Peptides

O

HN Cl

O O

N

HO

O O

N H

561 Geodiamolide G Type: Simple cyclic depsipeptides. C28H38IN3O7 Glass. Source: Sponge Cymbastela sp. (Papua New Guinea). Pharm: Cytotoxic (U373, ED50 = 7.7 μg/mL, HEY, ED50 = 8.6 μg/mL). Ref: J. E. Coleman, et al, Tetrahedron, 1995, 51, 10653

O

HN O O

N HO I

O O

O

N H

562 Geodiamolide H Type: Simple cyclic depsipeptides. C34H44IN3O7 mp 186–189 °C, [α]D = +19.1° (c = 0.17, CHCl3). Source: Sponge Geodia sp. (Trinidad). Pharm: Cytotoxic (HOP-92, IC50 = 0.118 μmol/L, SF268, IC50 = 0.153 μmol/L, OVCAR-4, IC50 = 0.0186 μmol/L, A498, IC50 = 0.0948 μmol/L, UO-31, IC50 = 0.185 μmol/L, MDA-MB-231/ATCC, IC50 = 0.433 μmol/L, Hs578T, IC50 = 0.245 μmol/L). Ref: W. F. Tinto, et al, Tetrahedron, 1998, 54, 4451 OH

O HN I

HO

O O

N

O

NH O

1.14 Simple Cyclic Depsipeptides

227

563 Guangomide A Spicellamide B Type: Simple cyclic depsipeptides. C31H46N4O9 Cryst. (hexane/EtOAc/ MeOH), mp 255–257 °C, [α]D28 = −44.6° (c = 0.8, CHCl3); amorph. solid, [α]D24 = −19° (c = 0.11, MeOH). Source: An unidentified fungus 001314c from sponge Ianthella sp. (Papua New Guinea), marine fungus Spicellum roseum from sponge Ectyoplasia ferox (Caribbean Sea). Pharm: Antibacterial (Staphylococcus epidermidis and Enterococcus durans, weak) (Amagata, 2006); cytotoxic (neuroblastoma cells, moderate) (Kralj, 2007). Ref: T. Amagata, et al, JNP, 2006, 69, 1560│A. Kralj, et al, PM, 2007, 73, 366

H N

N O O

O

O O

O

N

O O

N H

14

OH

564 Guangomide B Spicellamide A Type: Simple cyclic depsipeptides. C31H46N4O8 Amorph. powder, [α]D28 = −18.1° (c = 0.9, CHCl3); amorph. solid, [α]D24 = −59.5° (c = 0.12, MeOH). Source: An unidentified fungus 001314c from sponge Ianthella sp. (Papua New Guinea), marine fungus Spicellum roseum from sponge Ectyoplasia ferox (Caribbean Sea). Pharm: Antibacterial (Staphylococcus epidermidis and Enterococcus durans, weak) (Amagata, 2006); cytotoxic (neuroblastoma cells, moderate) (Kralj, 2007). Ref: T. Amagata, et al, JNP, 2006, 69, 1560│A. Kralj, et al, PM, 2007, 73, 366

H N

N O O

O N H

O O

O

N

O O 14

565 Guineamide G Type: Simple cyclic depsipeptides. C42H55N5O7 Source: Cyanobacterium Lyngbya majuscula (Alotau Bay, Papua New Guinea). Pharm: Toxic (brine shrimp, potent); cytotoxic (mouse neuroblastoma cell line). Ref: B. Han, et al, J. Microbiol. Biotechnol., 2011, 21, 930

228

1 Peptides

O O

N H O

N

O

O HN N

N

O

O

566 Haliclamide Type: Simple cyclic depsipeptides. C26H40N2O5 White amorphous solid, [α]D = −4.8° (c = 0.006 g/mL, CHCl3). Source: Sponge Haliclona sp. (order Haptosclerida, family Chalinidae, Vanuatu Islands, Australia). Pharm: Cytotoxic (NSCLC-N6, IC50 = 4.0 μg/mL). Ref: A. Randazzo, et al, Tetrahedron, 2001, 57, 4443 O N H

HOA

AHMA

O O

N O NMe-Phe

567 Halicylindramide A Type: Simple cyclic depsipeptides. C78H109BrN20O22S Solid, [α]D23 = −1.4° (c = 0.6, MeOH). Source: Sponge Halichondria cylindrata (Japan waters). Pharm: Antifungal (Mortierella ramanniana); cytotoxic (P388). Ref: H. -Y. Li, et al, JMC, 1995, 38, 338│ H. Seo, et al, JOC, 2009, 74, 906 NH O

H N

H N

S OH

O

O N HH H N N

O

O N O H HN

H N

H 2N

H N

H2N O

O

N H

O

N O

O HN

O

N O H2N O

Br

O

NH

O H O

O

HO N H NH O

OH

1.14 Simple Cyclic Depsipeptides

229

568 Halicylindramide B Type: Simple cyclic depsipeptides. C78H109BrN20O22S Solid, [α]D23 = −4.5° (c = 4.07, MeOH). Source: Sponge Halichondria cylindrata (Japan waters). Pharm: Antifungal (Mortierella ramanniana); cytotoxic (P388). Ref: H. Li, et al, JMC, 1995, 38, 338 Br

NH2 O

HO HN

H

O

O

O

O

N

N H

H2N

O

H N

N H

O

HO S O

O

O

H N

N H

O

H N

N H O

O

H

HN

O

O

O

NH2

HN

H N

HN

O

N H

O

O N H H N O

N H

569 Halicylindramide C Type: Simple cyclic depsipeptides. C79H111BrN20O22S Solid, [α]D23 = −6.1° (c = 0.52, MeOH). Source: Sponge Halichondria cylindrata (Japan waters). Pharm: Antifungal (Mortierella ramanniana); cytotoxic (P388). Ref: H. Li, et al, JMC, 1995, 38, 338 Br

NH2 O

HO HN

H

O O

O

O N

H 2N

O O

H

HN

O

O

N H

NH2

HN

N

HN

O N H O HO S O

O O

H N O

O

H N

N H

H N

N H

O

N H

O

O N H H N O

N H

570 Halicylindramide D Type: Simple cyclic depsipeptides. C73H100BrN19O20S Powder (Na salt), [α]D = +5.1° (c = 0.2, Me2CO aq) (Na salt). Source: Sponge Halichondria cylindrata (Japan waters). Pharm: Antifungal (Mortierella ramanniana, 5 μg/disk); cytotoxic (P388, IC50 = 2.1 μg/mL). Ref: H. Li, et al, JNP, 1996, 59, 163

230

1 Peptides

Br H N

O

O N

N H O

O

O H

N H

O S O

NH

O

H N

NH2

OH

N H

O

H N O NH2

HN

N H

O N H

O

N

H N

O HN

O O O O

O H N

NH O

NH2

571 Hantupeptin A Type: Simple cyclic depsipeptides. C41H60N4O8 Amorph. powder, [α]D25 = −41.5° (c = 1, MeOH). Source: Cyanobacterium Lyngbya majuscula. Pharm: Cytotoxic (Molt4, IC50 = 32 nmol/L; MCF7, IC50 = 4.0 μmol/L); toxic (brine shrimp, 10 ppm, 100% toxicity). Ref: Tripathi, A. et al, JNP, 2009, 72, 29

H

O O O

N

O

N H O O

H N

N O

O

7'

8'

572 Hantupeptin B Type: Simple cyclic depsipeptides. C41H62N4O8 Amorph. powder, [α]D25 = −41.5° (c = 0.4, MeOH). Source: Cyanobacterium Lyngbya majuscula (Pulau Hantu Besar, Singapore). Pharm: Cytotoxic (Molt4, IC50 = 0.2 μmol/L; MCF7, IC50 = 0.5 μmol/L); toxic (brine shrimp, 10 ppm, 100% toxicity). Ref: A. Tripathi, et al, Phytochemistry, 2010, 71, 307

H N

N

O O O

O

H N

H O O

N

O O

7'

8'

1.14 Simple Cyclic Depsipeptides

231

573 Hantupeptin C Type: Simple cyclic depsipeptides. C41H64N4O8 Amorph. powder, [α]D25 = −40.6° (c = 0.4, MeOH). Source: Cyanobacterium Lyngbya majuscula (Pulau Hantu Besar, Singapore). Pharm: Cytotoxic (Molt4, IC50 = 3.0 μmol/L; MCF7, IC50 = 1.0 μmol/L); toxic (brine shrimp, 100 ppm, 100% toxicity). Ref: A. Tripathi, et al, Phytochemistry, 2010, 71, 307

H

N

O O O

N

O

H O

N

O

H N

O 7'

O

8'

574 Homocereulide Type: Simple cyclic depsipeptides. C58H98N6O18 Colorless powder, [α]D = +10.5° (c = 0.12, MeOH). Source: Marine-derived bacterium Bacillus cereus SCRC-4h1-2 from prosobranch Littorina sp. (surface). Pharm: Cytotoxic (P388, IC50 = 0.033 ng/mL, Colon26, IC50 = 0.0014 ng/mL). Ref: G. -Y. -S. Wang, et al, Chem. Lett., 1995, 791

O O

O

H N

O

O O

NH

O

O

O

HN O

O

HN

O

O O

H N

O

O

NH

O

O

575 Ibu-epi-demethoxylyngbyastatin 3 Type: Simple cyclic depsipeptides. C51H82N8O11 Colorless amorphous solid, [α]D21 = −48.6° (c = 0.5, CH2Cl2). Source: Cyanobacterium Leptolyngbya sp. (SS Thistlegorm shipwreck, Red Sea). Pharm: Cytotoxic (neuro-2a, IC50 > 10 μmol/L). Ref: C. C. Thornburg, et al, JNP, 2011, 74, 1677

232

1 Peptides

O O

N

O

O

N H O

N

H N

N

O

N

H N

O

N H

O

O

O

O

576 Isaridin G Type: Simple cyclic depsipeptides. C36H55N5O8 Source: Marine-derived fungus Beauveria felina EN-135. Pharm: Antibacterial (Escherichia coli, MIC = 64 μg/mL, first report of antibacterial activity of the isaridins). Ref: F. Y. Du, et al, JNP, 2014, 77, 1164 OH O

O

N

H N

O O

O N N H O

N

O

577 Isokahalalide F Elisidepsin Type: Simple cyclic depsipeptides. C75H124N14O16 Source: Green alga Bryopsis pennata. Pharm: Antineoplastic. Ref: Y. H. Ling, et al, Eur. J. Cancer, 2009, 45, 1855│Coronado, C. et al, Drugs of the Future, 2010, 35, 287 NH2 O O H

N H

O N H H O

HN

O

HN H

NH

O H

O

O

NH N H

H

O

N O

NH

H N

O

O

O

HO NH S

O

H N

O

NH

1.14 Simple Cyclic Depsipeptides

233

578 Itralamide B Type: Simple cyclic depsipeptides. C38H58Cl2N6O8 Oil. Source: Cyanobacterium Lyngbya majuscula. (True Blue Bay, Grenada). Pharm: Cytotoxic (HEK-293). Ref: J. I. Jiménez, et al, JNP, 2009, 72, 1573

O N N

O

N H

O

H N

O

O O

O N

Cl

N O

Cl

579 Jasplakinolide Jaspamide Type: Simple cyclic depsipeptides. C36H45BrN4O6 [α]D = +35° (c = 3.62, MeOH). Source: Sponges Jaspis sp. (Makassar, Indonesia), Jaspis sp. (east coast of Malaysia, 1994), Jaspis sp. (Kudat, Malaysia, 1991), Jaspis splendens (overall yield = 6.6%) and Auletta sp. 02137, Jaspis johnstoni, Auletta cf. constricta, Hemiasterella minor and Cymbastela sp. Pharm: Cytotoxic (Selected NCI’s 60 cell screen testing, RPMI8226, GI50 = 0.031 μmol/L; HOP-62, GI50 = 0.15 μmol/L; HCT15, GI50 = 0.69 μmol/L; SF539, GI50 = 0.30 μmol/L; M14, GI50 = 0.056 μmol/L; OVCAR-3, GI50 = 0.040 μmol/L; 786-0, GI50 = 0.020 μmol/L); cytotoxic (NCI’s developmental therapeutics program, HCT116, GI50 = 0.1 μmol/L); cytotoxic (interesting and valuable cancer cell growth inhibitor: P388, GI50 = 0.0080 μg/mL) (Pettit, 2008); cytotoxic (HCT116, GI50 = 0.04 μmol/L; MDA-MB-231, GI50 = 0.01 μmol/L); cytotoxic (selected NCI 60 cell line screening results, IGROV1, GI50 = 0.02 μmol/L; U251, GI50 = 0.07 μmol/L; NCI-H522, GI50 = 0.03 μmol/L; DU145, GI50 = 0.03 μmol/L; A498, GI50 = 0.03 μmol/L; LOX-IMVI, GI50 = 0.01 μmol/L); cytotoxic (MCF7, IC50 = (0.019 ± 0)μmol/L; HT29, IC50 = (0.035 ± 0)μmol/L); anticancer-Cell-Effect (model: CA46, IC50 = 0.03 μmol/L, PtK2, IC50 = 0.3 μmol/L, mechanism: cell cycle inhibition) (Marquez, 2002); actin polymerisation promoter (EC50 = (19 ± 0.5)μmol/L) (Marquez, 2002); microfilament disruption (HeLa cells microfilament disruption assay, 80 nmol/L active, F-actin inhibitor); antifungal (Cundidu albicuns, potent), anthelmintic; nematocide; insecticide. Ref: T. M. Zabriskie, et al, JACS, 1986, 108, 3123│P. Crews, et al, Tet. Lett., 1986, 27, 2797│J. C. Braekman, et al, JNP, 1987, 50, 994│K. S. Chu, et al, JOC, 1991, 56, 5196│A. V. R. Rao, et al, Tet. Lett., 1993, 7085│L. Du,et al, Curr. Opin. Drug Discovery Dev., 2001, 4, 215│B. L. Marquez, et al, JNP, 2002, 65, 866│C. Tanaka, et al, Tetrahedron, 2006, 62, 3536│G. R. Pettit, et al, JNP, 2008, 71, 438│F. Gala, et al, Tetrahedron, 2009, 65, 51│S. J. Robinson, et al, JMC, 2010, 53, 1651│K. R. Watts, et al, JNP, 2011, 74, 341

234

1 Peptides

HO

H N

Br

22

H N O

N

O O

31

O

15

O

NH

35

4

5

580 Jasplakinolide B Jaspamide B Type: Simple cyclic depsipeptides. C36H43BrN4O7 Glass, [α]D25 = +11.4° (c = 0.0014, CHCl3). Source: Sponges Auletta sp. 02137 and Jaspis splendens (Vanuatu). Pharm: Cytotoxic (Selected NCI’s 60 cell screen testing, RPMI8226, GI50 = 0.0019 μmol/L; HOP-62, GI50 = 0.14 μmol/L; HCT15, GI50 = 6.6 μmol/L; SF539, GI50 = 0.064 μmol/L; M14, GI50 = 0.053 μmol/L; OVCAR-3, GI50 = 0.11 μmol/L; 786-0, GI50 = 0.51 μmol/L); cytotoxic (NCI’s developmental therapeutics program, HCT116, GI50 < 0.001 μmol/L; MCF7, GI50 = 0.13 μmol/L); cytotoxic (NSCLC-N6, IC50 = 3.3 μg/mL). Ref: A. Zampella, et al, JNP, 1999, 62, 332│S. J. Robinson, et al, JMC, 2010, 53, 1651 HO

H N

Br

22

H N O

N

O O 35

31

O O

15

NH

5 4

O

581 Jasplakinolide C Jaspamide C Type: Simple cyclic depsipeptides. C36H45BrN4O7 Glass, [α]D25 = +25.4° (c = 0.0013, CHCl3). Source: Sponge Jaspis splendens (Vanuatu). Pharm: Cytotoxic (NSCLC-N6, IC50 = 1.1 μg/mL); cytotoxic (MCF7, IC50 = (2.0 ± 0)μmol/L; HT29, IC50 = (2.6 ± 0.3)μmol/L). Ref: A. Zampella, et al, JNP, 1999, 62, 332│F. Gala, et al, Tetrahedron, 2009, 65, 51

1.14 Simple Cyclic Depsipeptides

235

OH

O HN

O

22

O N H

O

N Br

15

H N

31

HO 4

5 35

1

O

582 Jasplakinolide D Jaspamide D Type: Simple cyclic depsipeptides. C37H47BrN4O6 Amorph. solid, [α]D25 = +20.1° (c = 0.05, CHCl3). Source: Sponge Jaspis splendens. Pharm: Cytotoxic (HCT116, GI50 = 0.02 μmol/L; MDA-MB-231, GI50 = 0.02 μmol/L); cytotoxic (MCF7, IC50 = (0.05 ± 0)μmol/L; HT29, IC50 = (0.08 ± 0)μmol/L); cytotoxic (selected NCI 60 cell line screening results, IGROV1, GI50 = 0.008 μmol/L; U251, GI50 = 0.01 μmol/L; NCI-H522, GI50 = 0.03 μmol/L; DU145, GI50 = 0.02 μmol/L; A498, GI50 = 0.002 μmol/L; LOX-IMVI, GI50 = 0.003 μmol/L). Ref: F. Gala, et al, Tetrahedron, 2008, 64, 7127│F. Gala, et al, Tetrahedron, 2009, 65, 51│K. R. Watts, et al, JNP, 2011, 74, 341 HO

H N

Br

H N N O

O

O

O O

NH

583 Jasplakinolide E Jaspamide E Type: Simple cyclic depsipeptides. C36H45BrN4O7 Amorph. solid, [α]D25 = +42.2° (c = 0.05, CHCl3). Source: Sponges Auletta sp. 02137 and Jaspis splendens. Pharm: Cytotoxic (Selected NCI’s 60 cell screen testing, RPMI8226, GI50 = 0.022 μmol/L; HOP-62, GI50 = 0.14 μmol/L; HCT15, GI50 = 0.97 μmol/L; SF539, GI50 = 0.17 μmol/L; M14, GI50 = 0.078 μmol/L; OVCAR-3, GI50 = 0.53 μmol/L; 786-0, GI50 = 0.18 μmol/L); cytotoxic (NCI’s developmental therapeutics program, HCT116, GI50 = 0.14 μmol/L; MCF7, GI50 = 0.18 μmol/L); cytotoxic (MCF7, IC50 = (0.02 ± 0) μmol/L; HT29, IC50 = (0.02 ± 0)μmol/L). Ref: F. Gala, et al, Tetrahedron, 2007, 63, 5212; 2008, 64, 7127│F. Gala, et al, Tetrahedron, 2009, 65, 51│S. J. Robinson, et al, JMC, 2010, 53, 1651

236

1 Peptides

OH

O HN

O

22

O N H

O

N Br

15 31

5 4

H N

35

1

OH O

584 Jasplakinolide F Jaspamide F Type: Simple cyclic depsipeptides. C35H43BrN4O6 Amorph. solid, [α]D25 = −15.7° (c = 0.07, CHCl3). Source: Sponges Auletta sp. 02137, Jaspis splendens 00101 and Jaspis splendens. Pharm: Microfilament disruption (microfilament disruption assay, HeLa, 80 nmol/L active, F-actin inhibitor); cytotoxic (MCF7, IC50 = 30.0 μmol/L). Ref: F. Gala, et al, Tetrahedron, 2007, 63, 5212; 2008, 64, 7127│F. Gala, et al, Tetrahedron, 2009, 65, 51│S. J. Robinson, et al, JMC, 2010, 53, 1651 OH

O HN

O

22

O N H

N Br

15 31

O H N

5 4 1

O

585 Jasplakinolide G Jaspamide G Type: Simple cyclic depsipeptides. C36H43BrN4O7 Amorph. solid, [α]D25 = −6.7° (c = 0.06, CHCl3). Source: Sponge Jaspis splendens. Pharm: Cytotoxic (MCF7, IC50 = (0.60 ± 0.07)μmol/L; HT29, IC50 = (1.66 ± 0.07)μmol/L). Ref: F. Gala, et al, Tetrahedron, 2007, 63, 5212; 2008, 64, 7127│F. Gala, et al, Tetrahedron, 2009, 65, 51

1.14 Simple Cyclic Depsipeptides

237

OH

O HN

O

22

O N H

O

N Br

15

H N

31

5 4Z 35

1

O O

586 Jasplakinolide H Jaspamide H Type: Simple cyclic depsipeptides. C35H43BrN4O6 Amorph. solid, [α]D25 = +1.8° (c = 0.1, CHCl3). Source: Sponge Jaspis splendens. Pharm: Cytotoxic (MCF7, IC50 = 30 μmol/L). Ref: F. Gala, et al, Tetrahedron, 2007, 63, 5212; 2008, 64, 7127│F. Gala, et al, Tetrahedron, 2009, 65, 51 H N

Br HO 22

H N O

O

N O 35

6 5

31

O O

15

NH

4

587 Jasplakinolide J Jaspamide J Type: Simple cyclic depsipeptides. C35H43BrN4O6 Amorph. solid, [α]D25 = −4.1° (c = 0.02, CHCl3). Source: Sponge Jaspis splendens. Pharm: Cytotoxic (HCT116, GI50 = 0.11 μmol/L; MDA-MB-231, GI50 = 0.26 μmol/L); cytotoxic (MCF7, IC50 = (5.0 ± 0)μmol/L); cytotoxic (selected NCI 60 cell line screening results, IGROV1, GI50 = 0.02 μmol/L; U251, GI50 = 0.05 μmol/L; NCI-H522, GI50 = 0.61 μmol/L; DU145, GI50 = 0.29 μmol/L; A498, GI50 = 0.21 μmol/L; LOX-IMVI, GI50 = 0.03 μmol/L). Ref: F. Gala, et al, Tetrahedron, 2008, 64, 7127│F. Gala, et al, Tetrahedron, 2009, 65, 51│K. R. Watts, et al, JNP, 2011, 74, 341

238

1 Peptides

HO

H N

Br

H N N O

O

O

O O

NH

588 Jasplakinolide K Jaspamide K Type: Simple cyclic depsipeptides. C36H45BrN4O7 Amorph. solid, [α]D25 = −35° (c = 0.02, CHCl3). Source: Sponge Jaspis splendens. Pharm: Cytotoxic (MCF7, IC50 = (0.48 ± 0.09)μmol/L; HT29, IC50 = (0.90 ± 0.07)μmol/L). Ref: F. Gala, et al, Tetrahedron, 2007, 63, 5212; 2008, 64, 7127│F. Gala, et al, Tetrahedron, 2009, 65, 51 H N

Br HO 22

H N

O

O

N O 35

5

4

O

31 15

O

NH

3

OH

589 Jasplakinolide L Jaspamide L Type: Simple cyclic depsipeptides. C36H45BrN4O7 Amorph. solid, [α]D25 = −4° (c = 0.02, CHCl3). Source: Sponge Jaspis splendens. Pharm: Cytotoxic (MCF7, IC50 = 0.61 μmol/L). Ref: F. Gala, et al, Tetrahedron, 2007, 63, 5212; 2008, 64, 7127│F. Gala, et al, Tetrahedron, 2009, 65, 51 H N

Br HO 22

H N

O

O HO

5

N O 35

4

31

O O

15

NH

1.14 Simple Cyclic Depsipeptides

239

590 Jasplakinolide M Jaspamide M Type: Simple cyclic depsipeptides. C35H43BrN4O6 Amorph. solid, [α]D25 = +20.6° (c = 0.03, CHCl3). Source: Sponge Jaspis splendens (Vanuatu). Pharm: Cytotoxic (MCF7, IC50 = (0.10 ± 0)μmol/L; HT29, IC50 = (0.18 ± 0)μmol/L); cytotoxic (HCT116, GI50 = 0.13 μmol/L; MDA-MB-231, GI50 = 0.21 μmol/L); cytotoxic (selected NCI 60 cell line screening results, IGROV1, GI50 = 0.03 μmol/L; U251, GI50 = 0.06 μmol/L; NCI-H522, GI50 = 0.20 μmol/L; DU145, GI50 = 0.25 μmol/L; A498, GI50 = 0.17 μmol/L; LOX-IMVI, GI50 = 0.02 μmol/L). Ref: F. Gala, et al, Tetrahedron, 2009, 65, 51│K. R. Watts, et al, JNP, 2011, 74, 341 H N

Br HO 22

H N

O

NH O

O

35

31

O

15

O

NH

4 5

591 Jasplakinolide N Jaspamide N Type: Simple cyclic depsipeptides. C36H45BrN4O7 Amorph. solid, [α]D25 = −41.4° (c = 0.07, CHCl3). Source: Sponge Jaspis splendens (Vanuatu). Pharm: Cytotoxic (MCF7, IC50 = 33 μmol/L). Ref: F. Gala, et al, Tetrahedron, 2009, 65, 51 H N

Br HO

HO 22

H N

O

O

N O 35

5

O O

31 15

NH

4

592 Jasplakinolide O Jaspamide O Type: Simple cyclic depsipeptides. C35H46N4O7 Amorph. solid, [α]D25 = −70° (c = 0.02, CHCl3). Source: Sponge Jaspis splendens (Vanuatu). Pharm: Cytotoxic (MCF7, IC50 = (0.38 ± 0.09)μmol/L; HT29, IC50 = (0.30 ± 0)μmol/L). Ref: F. Gala, et al, Tetrahedron, 2009, 65, 51

240

1 Peptides

NH2

HO O

H N O

O

N O

O O

NH

593 Jasplakinolide P Jaspamide P Type: Simple cyclic depsipeptides. C37H48N4O9 Amorph. solid, [α]D25 = −85° (c = 0.02, CHCl3) (Jaspis splendens). [α]D27 = +61.6° (c = 0.06, MeOH) (Auletta sp.). Source: Sponges Auletta sp. 02137 and Jaspis splendens. Pharm: Cytotoxic (NCI’s developmental therapeutics program, HCT116, GI50 = 0.35 μmol/L; MCF7, GI50 = 4.9 μmol/L). Ref: F. Gala, et al, Tetrahedron, 2009, 65, 51│S. J. Robinson, et al, JMC, 2010, 53, 1651

HO NH

O O

H N

O

O O

O

N O O

NH

594 21-epi-Jasplakinolide P 21-epi-Jaspamide P Type: Simple cyclic depsipeptides. C37H48N4O9 Glass, [α]D27 = +39.2° (c = 0.07, MeOH). Source: Sponge Auletta sp. 02137 Pharm: Cytotoxic (NCI’s developmental therapeutics program, HCT116, GI50 = 0.38 μmol/L; MCF7, GI50 = 2.4 μmol/L). Ref: S. J. Robinson, et al, JMC, 2010, 53, 1651

1.14 Simple Cyclic Depsipeptides

241

HO NH

O

21

O

H N

O

O

N

O O

O O

NH

595 Jasplakinolide Q Jaspamide Q Type: Simple cyclic depsipeptides. C36H46N4O6 White amorphous solid, [α]D20 = −62° (c = 0.01, CHCl3). Source: Sponge Jaspis splendens. Pharm: Cytotoxic (HCT116, GI50 = 0.05 μmol/L; MDA-MB-231, GI50 = 0.07 μmol/L); cytotoxic (selected NCI 60 cell line screening results, IGROV1, GI50 = 0.01 μmol/L; U251, GI50 = 0.03 μmol/L; NCI-H522, GI50 = 0.16 μmol/L; DU145, GI50 = 0.10 μmol/L; A498, GI50 = 0.08 μmol/L; LOX-IMVI, GI50 = 0.02 μmol/L); cytotoxic (L5178Y, IC50 < 0.1 μg/mL). Ref: K. R. Watts, et al, JNP, 2011, 74, 341│S. S. Ebada, et al, Mar. Drugs, 2009, 7, 435 OH

O HN

O O

N H

N

O NH O

596 (–)-Jasplakinolide R Jaspamide R Type: Simple cyclic depsipeptides. C36H44Br2N4O6 White amorphous solid, [α]D20 = −100.0° (c = 0.01, CHCl3). Source: Sponge Jaspis splendens. Pharm: Cytotoxic (L5178Y, IC50 < 0.1 μg/mL). Ref: S. S. Ebada, et al, Mar. Drugs, 2009, 7, 435

242

1 Peptides

OH

O

Br HN

O O

N H

O

N Br

NH O

597 (+)-Jasplakinolide R1 Type: Simple cyclic depsipeptides. C36H44Br2N4O6 White solid, [α]D24 = +48° (c = 0.05, MeOH); Source: Sponge Jaspis splendens. Pharm: Cytotoxic (HCT116, GI50 = 0.06 μmol/L; MDA-MB-231, GI50 = 0.09 μmol/L); cytotoxic (selected NCI 60 cell line screening results, IGROV1, GI50 = 0.03 μmol/L; U251, GI50 = 0.03 μmol/L; NCI-H522, GI50 = 0.003 μmol/L; DU145, GI50 = 0.31 μmol/L; A498, GI50 = 0.04 μmol/L; LOX-IMVI, GI50 = 0.04 μmol/L). Ref: A. M. J. Senderowicz, et al, J. Natl. Cancer Inst., 1995, 87, 46│K. R. Watts, et al, JNP, 2011, 74, 341 HO

Br

N Br H N N O

O O

O O

NH

598 Jasplakinolide S Jaspamide S Type: Simple cyclic depsipeptides. C36H46N4O6 Glass, [α]D27 = +36.8° (c = 0.06, MeOH). Source: Sponge Auletta sp. 02137 Pharm: Cytotoxic (NCI’s developmental therapeutics program, HCT116, GI50 = 0.81 μmol/L; MCF7, GI50 = 2.3 μmol/L). Ref: S. J. Robinson, et al, JMC, 2010, 53, 1651

1.14 Simple Cyclic Depsipeptides

HO

243

H N

O HO H N

N

O O

O

O O

NH

599 (+)-Jasplakinolide V Jaspamide V Type: Simple cyclic depsipeptides. C36H45BrN4O7 White solid, [α]D23 = +120° (c = 0.05, MeOH). Source: Sponge Jaspis splendens (Korovou Bay, Fiji). Pharm: Cytotoxic (HCT116, GI50 = 0.07 μmol/L; MDA-MB-231, GI50 = 0.09 μmol/L); cytotoxic (selected NCI 60 cell line screening results, IGROV1, GI50 = 0.03 μmol/L; U251, GI50 = 0.04 μmol/L; NCI-H522, GI50 = 0.06 μmol/L; DU145, GI50 = 0.08 μmol/L; A498, GI50 = 0.01 μmol/L; LOX-IMVI, GI50 = 0.007 μmol/L). Ref: A. M. J. Senderowicz, et al, J. Natl. Cancer Inst., 1995, 87, 46│K. R. Watts, et al, JNP, 2011, 74, 341 H N

OH

HO

Br H N N O

O O

O O

NH

600 (+)-Jasplakinolide W Type: Simple cyclic depsipeptides. C36H43BrN4O7 White solid, [α]D23 = +60° (c = 0.05, MeOH). Source: Sponge Jaspis splendens. Pharm: Cytotoxic (HCT116, GI50 = 3.84 μmol/L; MDA-MB-231, GI50 = 2.32 μmol/L). Ref: A. M. J. Senderowicz, et al, J. Natl. Cancer Inst., 1995, 87, 46│K. R. Watts, et al, JNP, 2011, 74, 341 OH H N

HO Br H N

N

O O

O

O O

NH

244

1 Peptides

601 Jimycin A Type: Simple cyclic depsipeptides. C44H62N8O11 Source: Marine-derived streptomycete Streptomyces sp. (sediment, Nasese, Fiji). Pharm: Antibacterial (three MRSAs). Ref: P. Sun, et al, Bioorg. Med. Chem., 2011, 19, 6557 OH O OH

N

N

HN

H N

O

O

N

O

O

O

O

N

HN N

O

O

602 Jimycin B Type: Simple cyclic depsipeptides. C42H66N8O11 Source: Marine-derived streptomycete Streptomyces sp. (sediment, Nasese, Fiji). Pharm: Antibacterial (three MRSAs). Ref: P. Sun, et al, Bioorg. Med. Chem., 2011, 19, 6557 OH O OH

HN

H N

N

N

O

O

O

O

O O

N

O

HN

N

N O

603 Jimycin C Type: Simple cyclic depsipeptides. C44H62N8O11 Source: Marine-derived streptomycete Streptomyces sp. (sediment, Nasese, Fiji). Pharm: Antibacterial (three MRSAs). Ref: P. Sun, et al, Bioorg. Med. Chem., 2011, 19, 6557

1.14 Simple Cyclic Depsipeptides

245

OH O OH

N

N

HN

H N

O

O

N

O

O

O

O

N

HN N

O

O

604 Kahalalide A Type: Simple cyclic depsipeptides. C46H67N7O11 [α]D = −19° (c = 1, MeOH). Source: Sacoglossan Elysia rufescens which feeds on green alga Bryopsis sp. Pharm: Antituberculosis (Mycobacterium tuberculosis H37Rv, 12.5 μg/mL, InRt = 83%). Ref: M. T. Hamann, et al, J ACS, 1993, 115, 5825│M. T. Hamann,et al, JOC, 1996, 61, 6594│A.E.-S. Khalid, et al, Tetrahedron, 2000, 56, 949

O

O N H

H N

H N

N H

O O

O OH

O

NH

O O

HO N H O

NH

605 Kempopeptin A Type: Simple cyclic depsipeptides. C50H70N8O13 Amorph. solid, [α]D20 = −45° (c = 0.05, MeOH). Source: Cyanobacterium Lyngbya sp. Pharm: Anticancer-CellEffect (model: bovine pancreatic α-chymotrypsin, porcine pancreatic elastase, mechanism: serine Protease Inhibition); serine protease selective inhibitor (elastase, IC50 = 0.32 μmol/L; chymotripsin, IC50 = 2.6 μmol/L; trypsin, IC50 > 67 μmol/L). Ref: K. Taori, et al, JNP, 2008, 71, 1625

246

1 Peptides

OH

O

O

N O

HO

N

O

O

N H

N H

O HN

H H N

H H N

N

H O O OH

O

O

606 Kempopeptin B Type: Simple cyclic depsipeptides. C46H73BrN8O11 Amorph. powder, [α]D20 = −18° (c = 0.16, MeOH). Source: Cyanobacterium Lyngbya sp. Pharm: Anticancer-CellEffect (model: trypsin, mechanism: serine Protease Inhibition); serine protease selective inhibitor (elastase, IC50 > 67 μmol/L; chymotripsin, IC50 > 67 μmol/L; trypsin, IC50 = 8.4 μmol/L). Ref: K. Taori, et al, JNP, 2008, 71, 1625 O Br O

O

N H

N O

H HO

N

H H N

O

O N H

O HN

O

H N O

O

NH2

607 Koshikamide B Type: Simple cyclic depsipeptides. C93H150N24O28 [α]D = −120° (c = 0.1, 1–propanol aq). Source: Lithistid sponge Theonella sp. (off Shimokoshiki I., Kagoshima, Japan; Palau). Pharm: Cytotoxic (P388, IC50 = 0.22 μmol/L; HCT116, IC50 = 3.7 μmol/L). Ref: T. Araki, et al, JOC, 2008, 73, 7889│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)

1.14 Simple Cyclic Depsipeptides

O O N

N

N H

O

O NH2 H H N

O

O NH2

O

O

NH2

O

N

N H

O

N H

O

HN

H

O

O H 2N

N

H

O N

O

O

O NH

N

O

H 2N

O

3

2

H N

N H

O

O

3'

O

NH

H NH

HO

H N

O O N

247

O

NH

O

O

608 Koshikamide F Type: Simple cyclic depsipeptides. C93H148N24O27 Amorph. powder, [α]D23 = −79.1° (c = 0.23, MeOH). Source: Lithistid sponges Theonella swinhoei and Theonella cupola (deep water, Mutremdiu Reef, Palau). Pharm: Anti-HIV (single round HIV-1 neutralization assay, SF162 strain, IC50 = 2.3 μmol/L). Ref: A. Plaza, et al, JOC, 2010, 75, 4344│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev) O O N

N

N H

O

H H N O

O NH2

O N H O

NH2

O

N

N H

O

O HN

H

O

O H 2N

O NH2

N

H

O

O N

O

NH

N O O

H N

H2N

O

N

NH

H NH

H N

2

O

3'

O

O

O

3

N H

O

O

NH O

O

609 Koshikamide H Type: Simple cyclic depsipeptides. C94H152N24O28 Amorph. powder, [α]D23 = −84.6° (c = 0.4, MeOH). Source: Lithistid sponge Theonella swinhoei. Pharm: Anti-HIV (single round HIV-1 neutralization assay, SF162 strain, IC50 = 5.5 μmol/L); cytotoxic

248

1 Peptides

(HCT116, IC50 = 10 μmol/L). Ref: A. Plaza, et al, JOC, 2010, 75, 4344│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev) O O N

N

O H 2N

N

H

O

H H N

N H

O

O NH2

O

O NH2

O N H O

NH2

O

N

N H

O

O HN

H

O

O N

O

NH

N O

O N

H

H N

H2N

O

2

H

NH

NH

HO

H N O

3'

O

NH

O

O

3

N H

O

O

O

O

610 Kulokainalide 1 Type: Simple cyclic depsipeptides. C48H70N6O10 Amorph. solid, [α]D20 = −56° (c = 1.0, MeOH). Source: Cephalaspid Philinopsis speciosa (Hawaii). Pharm: Cytotoxic (P388, moderate). Ref: Y. Nakao, et al, JOC, 1998, 63, 3272

H N HN

O

N

N O

O

O O H N

O O

O

O

N

O

611 Kulokekahilide 1 Type: Simple cyclic depsipeptides. C53H74N6O10 Amorph. solid, [α]D = +22° (c = 0.07, MeOH). Source: Cephalaspid Philinopsis speciosa (Hawaii). Pharm: Cytotoxic (P388, IC50 = 2.1 μg/mL). Ref: J. Kimura, et al, JOC, 2002, 67, 1760

1.14 Simple Cyclic Depsipeptides

N

H HN

O H

O

N O

O O

N

O

O

249

H

O O

N

O

N H H

612 Kulokekahilide 2 Type: Simple cyclic depsipeptides. C44H67N5O10 Amorph. solid, [α]D = −15° (c = 0.04, MeOH). Source: Cephalaspid Philinopsis speciosa (Hawaii). Pharm: Cytotoxic (P388, SK-OV-3, MDA-MB-435 and A-10, IC50 = 4.2–59.1 nmol/L, selective). Ref: Y. Nakao, et al, JNP, 2004, 67, 1332│Y. Takada, et al, Tet. Lett., 2008, 49, 1163; 2009, 50, 840

O O

O NH O

O

OH

O

H N

H

NH

O O N

N O

613 Kulolide 1 Type: Simple cyclic depsipeptides. C43H63N5O9 Amorph. solid, [α]D20 = −102° (c = 1, MeOH). Source: Cephalaspid Philinopsis speciosa (Hawaii). Pharm: Cytotoxic (P388, moderate). Ref: M. T. Reese, et al, JACS, 1996, 118, 11081│Y. Nakao, et al, JOC, 1998, 63, 3272 H H N HN

O O O H N O

O

N O O

O

N O

250

1 Peptides

614 Kulolide 2 Type: Simple cyclic depsipeptides. C43H65N5O9 Amorph. solid, [α]D31 = −59° (c = 1.0, MeOH). Source: Cephalaspid Philinopsis speciosa (Hawaii). Pharm: Cytotoxic (P388, moderate). Ref: Y. Nakao, et al, JOC, 1998, 63, 3272 H H N HN

O

O

O

N O O

O

O

N

H N

O

O

615 Kulolide 3 Type: Simple cyclic depsipeptides. C43H67N5O9 Amorph. solid, [α]D31 = −95.2° (c = 1.11, MeOH). Source: Cephalaspid Philinopsis speciosa (Hawaii). Pharm: Cytotoxic (P388, moderate). Ref: Y. Nakao, et al, JOC, 1998, 63, 3272 H H N HN

O

O

O

N O O

O

O

N

H N

O

O

616 Kulomoopunalide 1 Type: Simple cyclic depsipeptides. C39H64N4O8 Amorph. solid, [α]D31 = −63° (c = 0.67, MeOH). Source: Cephalaspid Philinopsis speciosa (Hawaii). Pharm: Cytotoxic (P388, moderate). Ref: Y. Nakao, et al, JOC, 1998, 63, 3272

O N

O O N

N O

O HN

O O

O

1.14 Simple Cyclic Depsipeptides

251

617 Kulomoopunalide 2 Type: Simple cyclic depsipeptides. C38H62N4O8 Amorph. solid, [α]D31 = −45° (c = 1.36, MeOH). Source: Cephalaspid Philinopsis speciosa (Hawaii). Pharm: Cytotoxic (P388, moderate). Ref: Y. Nakao, et al, JOC, 1998, 63, 3272

O

N

O O

N O

O HN

O

O

O

N

618 Lagunamide A Type: Simple cyclic depsipeptides. C45H71N5O10 Amorph. solid, [α]D26 = −36° (c = 0.5, MeOH). Source: Cyanobacterium Lyngbya majuscula (Pulau Hantu Besar, Singapore). Pharm: Cytotoxic (P388, IC50 = 6.4 nmol/L); antiplasmodial (Plasmodium falciparum, IC50 = 0.19 μmol/L); antiswarming (gram-negative bacterium Pseudomonas aeruginosa PA01, 100 ppm, exerted antiswarming activity 62% compared to control). Ref: A. Tripathi, et al, JNP, 2010, 73, 1810

O N

N O O

HN

H

O

O

O

H N H

OH

O

N O

H

40

O 41

619 Lagunamide B Type: Simple cyclic depsipeptides. C45H69N5O10 Amorph. solid, [α]D25 = −39° (c = 0.5, MeOH). Source: Cyanobacterium Lyngbya majuscula (Pulau Hantu Besar, Singapore). Pharm: Cytotoxic (P388, IC50 = 20.5 nmol/L); antiplasmodial (Plasmodium falciparum, IC50 = 0.91 μmol/L); antiswarming (gram-negative bacterium Pseudomonas aeruginosa PA01, 100 ppm, exerted antiswarming activity 56% compared to control). Ref: A. Tripathi, et al, JNP, 2010, 73, 1810

252

1 Peptides

O N

N O HN

O

H

H N H

O

N

OH

O

O

O

O

H

O 41

40

620 Lagunamide C Type: Simple cyclic depsipeptides. C46H73N5O10 White amorphous solid, [α]D25 = −36° (c = 0.5, MeOH). Source: Cyanobacterium Lyngbya majuscula. (shallow waters during low tides at Pulua Hantu Besar, Singapore June 25, 2007). Pharm: Cytotoxic (MTT assay, panel of cancer cell lines, such as P388, A549, PC3, HCT8, and SK-OV-3 with IC50 = 2.1–24.4 nmol/L); antiplasmodial (Plasmodium falciparum, IC50 = 0.29 μmol/L); antiswarming (gram-negative bacterium Pseudomonas aeruginosa PA01, 100 ppm, weak). Ref: A. Tripathi, et al, Phytochemistry, 2011, 72, 2369

O N

N O HN

O

O

N H

N 1

O

O

O

O 40

O

OH

621 Largamide A Type: Simple cyclic depsipeptides. C41H59N7O12 Amorph. powder, [α]D20 = −63° (c = 0.13, MeOH). Source: Cyanobacteria Lyngbya confervoides (Broward County, Fort Lauderdale, Florida), Oscillatoria sp. and Lyngbya confervoides (Port Everglades Inlet, Fort Lauderdale, Florida). Pharm: Anticancer-Cell-Effect (model: porcine pancreatic elastase, mechanism: serine protease inhibition); serine protease selective inhibitor (elastase, IC50 = 1.41 μmol/L; chymotripsin, 50 μmol/L inactive; trypsin, 50 μmol/L inactive). Ref: A. Plaza, et al, JOC, 2006, 71, 6898; 2009, 74, 486│S. Matthew, et al, PM, 2009, 75, 528│S. Matthew, et al, Phytochemistry, 2009, 70, 2058

1.14 Simple Cyclic Depsipeptides

253

HOOC H N

HN

O HN

O O N H

H N

O

N H

O

O

OO

HN O

HO

622 Largamide B Type: Simple cyclic depsipeptides. C46H61N7O13 Amorph. powder, [α]D20 = −71.5° (c = 0.3, MeOH). Source: Cyanobacteria Lyngbya confervoides (Broward County, Fort Lauderdale, Florida), Oscillatoria sp. and Lyngbya confervoides (Port Everglades Inlet, Fort Lauderdale, Florida). Pharm: Anticancer-Cell-Effect (model: porcine pancreatic elastase, mechanism: serine protease inhibition); serine protease selective inhibitor (elastase, IC50 = 0.53 μmol/L; chymotripsin, 50 μmol/L inactive; trypsin, 50 μmol/L inactive). Ref: A. Plaza, et al, JOC, 2006, 71, 6898; 2009, 74, 486│S. Matthew, et al, PM, 2009, 75, 528│S. Matthew, et al, Phytochemistry, 2009, 70, 2058 HOOC H N

HN O O N H

HO

H N O

HN O N H

O HN

O

OO O

OH

623 Largamide C Type: Simple cyclic depsipeptides. C47H63N7O13 Amorph. powder, [α]D20 = −60.4° (c = 0.27, MeOH). Source: Cyanobacteria Lyngbya confervoides (Broward County, Fort Lauderdale, Florida), Oscillatoria sp. and Lyngbya confervoides (Port Everglades Inlet, Fort Lauderdale, Florida). Pharm: Anticancer-Cell-Effect (model: porcine pancreatic elastase, mechanism: serine protease inhibition); serine protease selective inhibitor (elastase, IC50 = 1.15 μmol/L; chymotripsin, 50 μmol/L inactive; trypsin, 50 μmol/L inactive). Ref: A. Plaza, et al, JOC, 2006, 71, 6898; 2009, 74, 486│S. Matthew, et al, PM, 2009, 75, 528│S. Matthew, et al, Phytochemistry, 2009, 70, 2058

254

1 Peptides

HOOC H N

HN O

O O N H

H N

O

N H

O

O

HN

OO

HN O

HO

HO

624 Lyngbyastatin 1 Type: Simple cyclic depsipeptides. C51H82N8O12 Glassy oil, [α]D27 = −17° (c = 0.3, MeOH). Source: Cyanobacteria Lyngbya majuscula and Schizothrix calcicola (assemblage, Guam). Pharm: Anticancer-Cell-Effect (model: rat aorta A-10 cells, mechanism: cellular microfilament disruption); cytokinesis inhibitor, cellular microfilament disrupter. Ref: G. R. Pettit, et al, Heterocycles 1989, 28, 553│G. G. Harrigan, et al, JNP 1998, 61, 1221 O N

O

N H

11

O

HN

O

15

N

O

O

O H

HN

O

N

N

N H

O O

O

O

625 Lyngbyastatin 2 Type: Simple cyclic depsipeptides. C56H94N6O13 Oil, [α]D27 = −218° (c = 0.04, MeOH). Source: Cyanobacterium Lyngbya majuscula (Guam). Pharm: Cytotoxic (KB, IC50 = 930 ng/mL; LoVo, IC50 = 475 ng/mL). Ref: T. Mutou, et al, JOC, 1996, 61, 6340│ H. Luesch, et al, JNP, 1999, 62, 1702

1.14 Simple Cyclic Depsipeptides

255

O N

N O

N O

O

O

O

55

N O

OH

O N

H

O

O O N 37

O

626 Lyngbyastatin 7 Type: Simple cyclic depsipeptides. C48H66N8O12 Amorph. powder, [α]D20 = −7.4° (c = 0.27, MeOH). Source: Cyanobacteria Lyngbya spp. (Florida). Pharm: AnticancerCell-Effect (model: porcine pancreatic elastase, mechanism: serine protease inhibition); serine protease selective inhibitor (elastase, IC50 = 3.3 μmol/L; chymotripsin, IC50 = 2.5 μmol/L; trypsin, 30 μmol/L inactive); elastase inhibitor. Ref: K. Taori, et al, JNP, 2007, 70, 1593 OH

O

O

N

N HO

O N H

O

H N

O O H N O

HN

N H

O

O O

NH2

627 Majusculamide C Type: Simple cyclic depsipeptides. C50H80N8O12 Solid, [α]D = −96° (c = 2.5, CH2Cl2). Source: Cyanobacteria Lyngbya majuscula and Lyngbya majuscula (deep water, variety), sponge Ptilocaulis trachys (Enewetak, Marshall Is., Pacific Ocean), sea hare Dolabella auricularia. Pharm: Cytotoxic (interesting and valuable cancer cell growth inhibitor: OVCAR-3, GI50 = 0.51 μg/mL; A498, GI50 = 0.058 μg/mL; NCI-H460, GI50 = 0.0032 μg/mL; KM20L2, GI50 = 0.0013 μg/mL; SK-MEL-5, GI50 = 0.0068 μg/mL; SF295, GI50 = 0.13 μg/mL) (Pettit, 2008); antifungal (plant pathogenic fungi). Ref: D. C. Carter, et al, JOC, 1984, 49, 236│D. E. Williams, et al, JNP, 1993, 56,

256

1 Peptides

545│R. B. Bates, et al, JACS, 1997, 119, 2111│Williams, P. G. et al, JNP, 2003, 66, 1356│G. R. Pettit, et al, JNP, 2008, 71, 438│H. Choi, et al, JNP, 2010, 73, 1411 O N H

O O

O N

O

H N

N H

O

O

H H N

N O

O

N

O

O 57

H

H N O

628 N,Nʹ-Methyleno-didemnin A Type: Simple cyclic depsipeptides. C50H78N6O12 Colorless glass, [α]D = −153° (c = 0.38, MeOH). Source: Ascidian Trididemnum solidum (Little San Salvador I., Bahamas). Pharm: Cytotoxic (HCT116, IC50 = 24 nmol/L). Ref: T. F. Molinski, et al, JNP, 2011, 74, 882 OH O O O

O

O O

NH O

N N

O

O

N

HN N

O

O

629 N-Methylsansalvamide Type: Simple cyclic depsipeptides. C33H52N4O6 Oil, [α]D = −132° (c = 0.41, CH2Cl2). Source: Marine-derived fungus Fusarium sp. CNL-619 from green alga Avrainvillea sp. (Caribbean Sea). Pharm: Cytotoxic (NCI’s cell line panel, GI50 = 8.3 μmol/L, weak). Ref: M. Cueto, et al, Phytochemistry, 2000, 55, 223 O 9

O

N O

N H O N H

O

O NH

257

1.14 Simple Cyclic Depsipeptides

630 Microspinosamide Type: Simple cyclic depsipeptides. C75H109BrN18O22S Amorph. powder, [α]D = +2.4° (c = 0.5, MeOH). Source: Sponge Sidonops microspinosa (Sulawesi). Pharm: AntiHIV. Ref: M. A. Rashid, et al, JNP, 2001, 64, 117 H N

O N H

O

H N H

O

O

O

H N

N H

N

S

O

H N

N H

O

OH

O

N H

O

O

Br

NH

H 2N

O

O H N H

H N

N O O

NH

NH2

O OH

HOOC

O

O

N

H N O

631 Mirabamide A Type: Simple cyclic depsipeptides. C72H114ClN13O25 Amorph. powder, [α]D23 = −3.4° (c = 0.06, MeOH). Source: Lithistid sponge Siliquariaspongia mirabilis (Nama I., southeast of Chuuk Lagoon, Federated States of Micronesia). Pharm: Anti-HIV (HIV-1 neutralization assay, host cell TZM-bl cell line, HXB2 (T-cell tropic) viral strain, IC50 = 140 nmol/L; SF162 (macrophage-tropic) viral strain, IC50 = 0.40 μmol/L); anti-HIV (HIV-1 fusion assay, LAV (T-cell tropic) viral strain, IC50 = 0.041 μmol/L); anti-HIV (HIV-1 neutralization assay, host cell TZM-bl cell line, IC50 = 1.8 μmol/L). Ref: A. Plaza, et al, JNP, 2007, 70, 1753│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev) HO H

O

HN O

NH

O

O HN

HO OH

NH2 Cl

O

H NH2

4'''

O

4''

H

N H

N H

O

O

HN O

O O

O

O H N

O

O

HO NH

NH

O O OH OH

OH N H

HN O

632 Mirabamide E Type: Simple cyclic depsipeptides. C72H112ClN13O24 Source: Sponge Stelletta calvosa (Torres Strait, Queensland, Australia). Pharm: Anti-HIV (HIV-1 neutralization assay, YU2-V3 viral strain, IC50 = 121 nmol/L). Ref: Z. Lu, et al, JNP, 2011, 74, 185│ P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)

258

1 Peptides

H N O HO

N H

O HN

H2N

Cl O

4''

N H

H 2N

OH

O

O O

O

O

HO

O

HN

O

NH

O O

OH OH

O O

NH

OH

N

H N

H N

O

O

4'''

N

O

O

633 Mirabamide F Type: Simple cyclic depsipeptides. C72H112ClN13O23 Source: Sponge Stelletta calvosa (Torres Strait, Queensland, Australia). Pharm: Anti-HIV (HIV-1 neutralization assay, YU2-V3 viral strain, IC50 = 62 nmol/L). Ref: Z. Lu, et al, JNP, 2011, 74, 185│ P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)

H N O HO

N H

O HN H 2N

H 2N O

O

Cl

O

O

4''

N H

O

O

HN O

O

HO

O O

NH

H N

N

O O OH OH

O

O NH

O

4'''

N

OH

H N O

634 Mirabamide G Type: Simple cyclic depsipeptides. C66H102ClN13O20 Source: Sponge Stelletta calvosa (Torres Strait, Queensland, Australia). Pharm: Anti-HIV (HIV-1 neutralization assay, YU2-V3 viral strain, IC50 = 68 nmol/L). Ref: Z. Lu, et al, JNP, 2011, 74, 185│ P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)

1.14 Simple Cyclic Depsipeptides

H N O

O HN

N H

HO

H2N O

Cl

O

O

4''

N H

H 2N

OH

O

O

OH

NH

O O

O

O NH

N

OH

H N

H N

O

4'''

N

O HN O

259

O

O

635 Mirabamide H Type: Simple cyclic depsipeptides. C66H102ClN13O19 Source: Sponge Stelletta calvosa (Torres Strait, Queensland, Australia). Pharm: Anti-HIV (HIV-1 neutralization assay, YU2-V3 viral strain, IC50 = 42 nmol/L). Ref: Z. Lu, et al, JNP, 2011, 74, 185│ P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)

H N O HO

N H

H 2N O

O

Cl

O

H 2N

O

4''

O HN

4'''

OH

N

N H

O

O

HN O

O O

O

O NH H N

O

NH

O

N

OH

H N O

636 Miuraenamide A Type: Simple cyclic depsipeptides. C34H42BrN3O7 Powder, [α]D25 = +59° (c = 0.15, MeOH). Source: Cyanobacterium Lyngbya sp., myxobacterium Paraliomyxa miuraensis SMH-27-4 (slightly halophilic). Pharm: Anticancer-Cell-Effect (model: HeLa, mechanism: actin filaments stabilization); antifungal (inhibits fungus Phytophthora sp., potent and selective). Ref: T. Iizuka, et al, J. Antibiot., 2006, 59, 385│E. Sumiya, et al, ACS Chem. Biol. 2011, 6, 425

260

1 Peptides

HO H N

Br

O

N O

O

O

O

HN O

637 Nagahamide A Type: Simple cyclic depsipeptides. C39H64N8O14 Powder, [α]D = +26.6° (c = 0.1, 1–propanol aq). Source: Lithistid sponge Theonella swinhoei (near Nagahama, Kamikoshiki-jima I., Japan). Pharm: Antibacterial (Escherichia coli and Staphylococcus aureus, 50 μg/disk, IZD = 7 mm, weak). Ref: Y. Okada, et al, Org. Lett., 2002, 4, 3039│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev) O NH2 O H N

H HN O

H O HO

O

HN HO

NH

H

O

N H O NH2 O

O OH

O

H N O

638 Neamphamide A Type: Simple cyclic depsipeptides. C75H125N21O23 Amorph. solid, [α]D21 = −0.6° (c = 0.2, MeOH). Source: Sponge Neamphius huxleyi. Pharm: Anti-HIV-1. Ref: N. Oku, et al, JNP, 2004, 67, 1407│N. Oku, et al, JOC, 2005, 70, 6842

NH2 OH H N

O N H HO

NH2

O

O

O

O

OH

O H

N H H H HN

O

NH HN

O

H H N

N H

NH OH H2N

N

NH2

O N H

H2N HO

O

H N

O

O O

H N

NH

O

O N

O

H O O

NH2

1.14 Simple Cyclic Depsipeptides

261

639 Neamphamide B Type: Simple cyclic depsipeptides. C71H119N19O21 Source: Sponge Neamphius huxleyi (Milln Reef, Cape Grafton, Queensland, Australia). Pharm: Cytotoxic (potent and non-selective). Ref: T. D. Tran, et al, JNP, 2012, 75, 2200 O

O NH2

O N H

HO

H N O

OH

NH2

O

O

N H

NH

O

O

HN O

NH

HN

O

N

NH2

O

O

HN H 2N

O

H N

N H

OH

OH HN

O

O N

N H

O

NH2

OH

640 Neamphamide C Type: Simple cyclic depsipeptides. C71H118N18O22 Source: Sponge Neamphius huxleyi (Milln Reef, Cape Grafton, Queensland, Australia). Pharm: Cytotoxic (potent and non-selective). Ref: T. D. Tran, et al, JNP, 2012, 75, 2200

NH2

O N H

HO

NH2

O

O

H N O

OH

O

OH

O

HN H2 N

O

H N

N H

NH2 OH HN N H

HN

O

HN

O

N

NH O

O

O

NH

O

O

O N

N H

O

OH

OH

641 Neamphamide D Type: Simple cyclic depsipeptides. C72H121N19O21 Source: Sponge Neamphius huxleyi (Milln Reef, Cape Grafton, Queensland, Australia). Pharm: Cytotoxic (potent and non-selective). Ref: T. D. Tran, et al, JNP, 2012, 75, 2200

262

1 Peptides

O

O NH2

O

H N

N H

OH

O

HO

NH2

O

OH

O

HN H 2N

O

H N

N H

NH2 OH HN N H

HN

O

HN

O

N

NH O

O

O

NH

O

O

O N

N H

O

NH2

OH

642 Neosiphoniamolide A Type: Simple cyclic depsipeptides. C29H42IN3O6 Amorphous solid, [α]D = +5.2°. Source: Lithistid sponge Neosiphonia superstes (New Caledonia). Pharm: Antifungal (fungi growth inhibitors, Piricularia oryzae and Helmintbosporium gramineum, IC90 = 5 μmol/L). Ref: M. V. D’Auria, et al, JNP, 1995, 58, 121 I OH

H N

N O HN

O

O

O

O

643 Nordolastatin G Type: Simple cyclic depsipeptides. C56H94N6O13 Amorph. powder, [α]D25 = −183° (c = 0.11, MeOH). Source: Cyanobacterium Lyngbya majuscula (Guam). Pharm: Cytotoxic (HeLa-S3, IC50 = 5.3 μg/mL). Ref: T. Mutou, et al, JOC, 1996, 61, 6340

1.14 Simple Cyclic Depsipeptides

263

O N

N O

N O

O

O

O

N O OH

O N O

O O N O

644 Norlyngbyastatin 2 Type: Simple cyclic depsipeptides. C55H92N6O13 Oil, [α]D27 = −179° (c = 0.05, MeOH). Source: Cyanobacterium Lyngbya majuscula (Guam). Pharm: Cytotoxic (KB, IC50 = 20 ng/mL; LoVo, IC50 = 14 ng/mL). Ref: T. Mutou, et al, JOC, 1996, 61, 6340│H. Luesch, et al, JNP, 1999, 62, 1702 O N

N O

N O

O

O

O

N O O

OH

N O

O O N O

645 57-Normajusculamide C Type: Simple cyclic depsipeptides. C49H78N8O12 Source: Cyanobacterium Lyngbya majuscula (deep-water variety). Pharm: Antifungal (yeast Saccharomyces pastorianus, indicator organism). Ref: J. S. Mynderse, et al, JNP, 1988, 51, 1299

264

1 Peptides

O

O N H

N

H O

H H N

N O

O

N

O

O O

O

O

H N

H

H

N

N

O

O

646 Onchidin Type: Simple cyclic depsipeptides. C60H98N6O14 [α]D25 = −140.9°. Source: Pulmonate Onchidium sp. (New Caledonia). Pharm: Cytotoxic (P388, IC50 = 8 μg/mL). Ref: J. Rodriguez, et al, Tet. Lett., 1994, 35, 9239 O

H N

O

HN

O

O

O

N

O

O

O

O

N

O

O O

O O

NH

N H

647 Palmyramide A Type: Simple cyclic depsipeptides. C36H53N3O9 Glass, [α]D = +19.6° (c = 0.25, CHCl3). Source: Cyanobacterium Lyngbya majuscula (Palmyra Atoll, Central Pacific Ocean). Pharm: Anticancer-Cell-Effect (model: neuro-2a, mechanism: Sodium channel inhibition, inhibits veratridine and ouabain induced Sodium overload, IC50 = 17.2 μmol/ L); cytotoxic (H460). Ref: M. Taniguchi, et al, JNP, 2010, 73, 393 O O

O

O O

O

O N H

N O

N

O

1.14 Simple Cyclic Depsipeptides

265

648 Papuamide A Type: Simple cyclic depsipeptides. C66H105N13O21 Amorph. glass, [α]D25 = +12° (c = 3.5, MeOH). Source: Lithistid sponges Theonella mirabilis (Papua New Guinea), Theonella swinhoee and Theonella spp. Pharm: Anti-HIV (HIV-1 neutralization assay, YU2-V3 viral strain, IC50 = 73 nmol/L; focus on extensive studies to define its mode of action); cytotoxic (HCT116, IC50 = 3.5 μmol/L); anti-HIV (inhibits infection of hmn T-lymphoblastoid cells by HIV-1RF, EC50 = 4 ng/mL); cytotoxic (panel of hmn cancer cell lines, mean IC50 = 75 ng/mL). Ref: P. W. Ford, et al, JACS, 1999, 121, 5899│A. E. Wright, Current Opinion in Biotechnology 2010, 21, 801│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643

OH

O

H H N

N OH H

O HN

OH

O O

H

NH2 HN

NH2 O

HN O O O

O

H

4''

O

N

NH

O

NH

O

O

H N

H

O

O O N

NH

H

4'''

OH

OH

649 Papuamide B Type: Simple cyclic depsipeptides. C65H103N13O21 Amorph. glass, [α]D25 = +12.9° (c = 0.13, MeOH). Source: Lithistid sponges Theonella mirabilis (Papua New Guinea), Theonella swinhoei and Theonella spp. Pharm: Anti-HIV (inhibits infection of hmn T-lymphoblastoid cells by HIV-1RF, EC50 = 4 ng/mL); cytotoxic. Ref: P. W. Ford, et al, JACS, 1999, 121, 5899│A. E. Wright, Current Opinion in Biotechnology, 2010, 21, 801│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)

266

1 Peptides

O

OH

OH

H H N

N H

O HN

OH

O O

H

NH2 HN

NH2 O

HN O O O

O

H

4''

O

N

NH

O

NH

O

H N

O

O O

4'''

NH

N H H

O

H

OH

OH

650 Phoriospongin A Type: Simple cyclic depsipeptides. C52H82ClN11O15 Amorph. solid, [α]D20 = +18° (c = 0.08, MeOH). Source: Sponges Callyspongia bilamellata and Phoriospongia spp. Pharm: Nematocide. Ref: R. J. Capon, et al, JNP, 2002, 65, 358 Cl H

O H 2N

NH

O N

N H

NH O

22

O

O

H

HO

NH

OH HN

O

O

O N H

H N

H N H

O

O

N H

O

O

O

651 Phoriospongin B Type: Simple cyclic depsipeptides. C53H84ClN11O15 Amorph. solid, [α]D20 = −6.2° (c = 0.13, MeOH). Source: Sponges Callyspongia bilamellata and Phoriospongia spp. Pharm: Nematocide. Ref: R. J. Capon, et al, JNP, 2002, 65, 358

1.14 Simple Cyclic Depsipeptides

267

Cl H

O H 2N

O N

N H

NH

NH O

22

O

O

H

O HO

NH O

OH HN

O

H

O

O

H N

N H

H N

N H

O

O

O

652 Pitipeptolide A Type: Simple cyclic depsipeptides. C44H65N5O9 Amorph. solid, [α]D25 = −109° (c = 1, MeOH). Source: Cyanobacterium Lyngbya majuscula (Piti Bomb Holes, Guam). Pharm: Cytotoxic (LoVo); elastase inducer (50 μg/mL, activity increased in 2.76-fold); antituberculosis (disc diffusion assay, inoculum Mycobacterium tuberculosis, 100 μg, IZD = 28 mm, 50 μg, IZD = 23 mm, 10 μg, IZD = 9 mm, control streptomycin 10 μg, IZD = 40 mm); cytotoxic (HT29, IC50 = 13 μmol/L, control paclitaxel, IC50 = 0.007 μmol/L; MCF7, IC50 = 13 μmol/L, control paclitaxel, IC50 = 0.006 μmol/L); stimulator of elastase; feeding deterrent (grazers of Lyngbya majuscula). Ref: H. Luesch, et al, JNP, 2001, 64, 304│E. Cruz-Rivera, et al, J. Chem. Ecol., 2007, 33, 213│R. Montaser, et al, Phytochemistry, 2011, 72, 2068 8

7

O N H

O O HN

N O

O

O

O O

H

N H

N H

O

653 Pitipeptolide B Type: Simple cyclic depsipeptides. C44H67N5O9 Amorph. solid, [α]D25 = −109° (c = 1, MeOH). Source: Cyanobacterium Lyngbya majuscula (Piti Bomb Holes, Guam). Pharm: Cytotoxic (LoVo); elastase inducer (50 μg/mL, activity increased in 2.55-fold); antituberculosis (disc diffusion assay, inoculum Mycobacterium tuberculosis, 100 μg, IZD = 30 mm, 50 μg, IZD = 24 mm, 10 μg, IZD = 14 mm, control streptomycin 10 μg, IZD = 40 mm); cytotoxic (HT29, IC50 = 13 μmol/L, control paclitaxel, IC50 = 0.007 μmol/L; MCF7, IC50 = 11 μmol/L, control paclitaxel, IC50 = 0.006 μmol/L).

268

1 Peptides

Ref: H. Luesch, et al, JNP, 2001, 64, 304│R. Montaser,; et al, Phytochemistry, 2011, 72, 2068 O

7 8

N

N H

O O

O

O

O

O O HN

H

N H

N H

O

654 Pitipeptolide C Type: Simple cyclic depsipeptides. C44H69N5O9 Colorless amorphous solid, [α]D20 = −121° (c = 0.11, MeOH). Source: Cyanobacterium Lyngbya majuscula (Guam). Pharm: Antituberculosis (inoculum Mycobacterium tuberculosis, disc diffusion assay, 100 μg, IZD = 26 mm, 50 μg, IZD = 21 mm, 10 μg, IZD = 18 mm, control Streptomycin 10 μg, IZD = 40 mm); cytotoxic (HT29, IC50 = 67 μmol/L, control Paclitaxel IC50 = 0.007 μmol/L; MCF7, IC50 = 73 μmol/L, Paclitaxel IC50 = 0.006 μmol/L). Ref: R. Montaser, et al, Phytochemistry, 2011, 72, 2068 O

O

O

N H

N

O O

NH O

NH O

O O

N

655 Pitipeptolide D Type: Simple cyclic depsipeptides. C43H63N5O9 Colorless amorphous solid, [α]D20 = −112° (c = 0.12, MeOH). Source: Cyanobacterium Lyngbya majuscula (Guam). Pharm: Antituberculosis (inoculum Mycobacterium tuberculosis, disc diffusion assay, 100 μg, IZD = 10 mm, 50 μg, IZD = 0 mm, 10 μg, IZD = 0 mm, control Streptomycin 10 μg, IZD = 40 mm); cytotoxic (HT29, IC50 > 100 μmol/L, control Paclitaxel IC50 = 0.007 μmol/L; MCF7, IC5 0 > 100 μmol/L, Paclitaxel IC50 = 0.006 μmol/L). Ref: R. Montaser, et al, Phytochemistry, 2011, 72, 2068

1.14 Simple Cyclic Depsipeptides

269

O O

N H

O

HN

O O

NH

O

O

O

NH N

O

656 Pitipeptolide E Type: Simple cyclic depsipeptides. C43H63N5O9 Colorless amorphous solid, [α]D20 = −105° (c = 0.13, MeOH). Source: Cyanobacterium Lyngbya majuscula (Guam). Pharm: Antituberculosis (inoculum Mycobacterium tuberculosis, disc diffusion assay, 100 μg, IZD = 21 mm, 50 μg, IZD = 15 mm, 10 μg, IZD = 0 mm, control Streptomycin 10 μg, IZD = 40 mm); cytotoxic (HT29, IC50 = 75 μmol/L, control Paclitaxel IC50 = 0.007 μmol/L; MCF7, IC50 > 100 μmol/L, Paclitaxel IC50 = 0.006 μmol/L). Ref: R. Montaser, et al, Phytochemistry, 2011, 72, 2068

O O

N H

O

N

O O

NH

O NH O

O O

N

657 Pitipeptolide F Type: Simple cyclic depsipeptides. C43H63N5O9 Colorless amorphous solid, [α]D20 = −101° (c = 0.10, MeOH). Source: Cyanobacterium Lyngbya majuscula (Guam). Pharm: Antituberculosis (inoculum Mycobacterium tuberculosis, disc diffusion assay, 100 μg, IZD = 40 mm, 50 μg, IZD = 30 mm, 10 μg, IZD = 10 mm, control Streptomycin 10 μg, IZD = 40 mm); cytotoxic (HT29, IC50 = 87 μmol/L, control Paclitaxel IC50 = 0.007 μmol/L; MCF7, IC50 = 83 μmol/L, Paclitaxel IC50 = 0.006 μmol/L). Ref: R. Montaser, et al, Phytochemistry, 2011, 72, 2068

270

1 Peptides

O

O

O

N H N

O O

NH O

O

O

NH N

O

658 Pitiprolamide Type: Simple cyclic depsipeptides. C50H73N5O10 Colorless amorphous solid, [α]D20 = −65° (c = 0.3, MeOH). Source: Cyanobacterium Lyngbya majuscula (Piti Bomb Holes, Guam). Pharm: Cytotoxic (HCT116 and MCF7, IC50 = 33 μmol/L for both); antibacterial (Bacillus cereus, IC50 = 70 μmol/L; Staphylococcus aureus or Pseudomonas aeruginosa, inactive); antituberculosis (Mycobacterium tuberculosis, 50 μg/disk). Ref: R. Montaser, et al, JNP, 2011, 74, 109 O

O N H

O O

O O

O

O N

N H

O N

O N

659 Polydiscamide A Type: Simple cyclic depsipeptides. C75H110BrN19O20S White powder (Na salt), mp 212–216 °C (Na salt), [α]D25 = −1.1° (c = 1.89, MeOH). Source: Lithistid sponge Discodermia sp. Pharm: Cytotoxic (A549, IC50 = 0.7 μg/mL); antibacterial (inhibits growth of Bacillus subtilis, MIC = 3.1 μg/mL). Ref: N. K. Gulavita, et al, JOC, 1992, 57, 1767

1.14 Simple Cyclic Depsipeptides

O

O O

H N

N H

N

O

H N

N H

H

NH NH

NH

O

O

O

O N H

HN

S

NH2

O

O

HN

O

O O H

N

HN

Br

H2N

O

H N

271

O N

O O O N H H

O

O NH2

660 Pompanopeptin A Type: Simple cyclic depsipeptides. C46H73BrN10O12S Amorph. solid, [α]D20 = −42.5° (c = 0.2, MeOH). Source: Cyanobacterium Lyngbya confervoides. Pharm: AnticancerCell-Effect (model: porcine pancreatic trypsin, mechanism: serine protease inhibition); serine protease selective inhibitor (trypsin, IC50 = 2.4 μmol/L). Ref: S. Matthew, et al, Tetrahedron, 2008, 64, 4081│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev) O Br O

O

N

H N HO

N H O

O

O O

H H N

H N

N H HN

O

O O

O HN

S

NH2 NH

661 Porpoisamide A Type: Simple cyclic depsipeptides. C33H50N4O6 Source: Cyanobacterium Lyngbya sp. (Florida Keys, USA). Pharm: Cytotoxic (HCT116 and U2OS, weak). Ref: T. Meickle, et al, Bioorg. Med. Chem., 2011, 19, 6576

272

1 Peptides

H N

HN O

O O

N

O

O

O N

662 Porpoisamide B Type: Simple cyclic depsipeptides. C33H50N4O6 Source: Cyanobacterium Lyngbya sp. (Florida Keys, USA). Pharm: Cytotoxic (HCT116 and U2OS, weak). Ref: T. Meickle, et al, Bioorg. Med. Chem., 2011, 19, 6576

H N

HN O

O O

N

O

O

O N

663 [D-Pro4]Didemnin B Type: Simple cyclic depsipeptides. C57H89N7O15 Amorph. solid. Source: Ascidian Trididemnum cyanophorum (Guadeloupe I.). Pharm: Cytotoxic (hmn lymphoblastic leukemia cell lines). Ref: E. Abou-Mansour, et al, Tetrahedron, 1995, 51, 12 591 O O N

2'''

O O

O

N O

NH O O

O

OH

O

NH NH

O N O N

HO

O

1.14 Simple Cyclic Depsipeptides

273

664 Salinamide C Type: Simple cyclic depsipeptides. C52H73N7O14 Off–white solid. Source: Marinederived streptomycete Streptomyces sp. CNB-091 from scyphomedusa Cassiopeia xamachana (surface, Florida Keys). Pharm: Anti-inflammatory. Ref: B. S. Moore, et al, JOC, 1999, 64, 1145 HO O O

OH O HN

N

O O

O

O

N H

HN

O

O Ph

O

H N

NH O

N H O

665 Salinamide D Type: Simple cyclic depsipeptides. C50H67N7O15 Pale yellow solid, [α]D = −54.4° (c = 0.85, CDCl3). Source: Marine-derived streptomycete Streptomyces sp. CNB-091 from scyphomedusa Cassiopeia xamachana (surface, Florida Keys). Pharm: Antiinflammatory. Ref: B. S. Moore, et al, JOC, 1999, 64, 1145 HO O O

OH O HN

O N

O O

O

O

N H

HN

O

H N

Ph O

NH O

N H O O

666 Salinamide E Type: Simple cyclic depsipeptides. C43H62N6O12 Off–white solid, [α]D = −93.4° (c = 1.35, CDCl3). Source: Marine-derived streptomycete Streptomyces sp. CNB-091 from scyphomedusa Cassiopeia xamachana (surface, Florida Keys). Pharm: Antiinflammatory. Ref: B. S. Moore, et al, JOC, 1999, 64, 1145

274

1 Peptides

HO O O

OH N H OH

HN O HN

O O

O

N

H N

O

Ph O

N H O

667 Sansalvamide A Sansalvamide Type: Simple cyclic depsipeptides. C32H50N4O6 Powdermp 143–152 °C, [α]D = −115° (c = 0.001, MeOH). Source: Marine-derived fungus Fusarium sp. from seagrass Holodule wrightii (surface, Little San Salvador I., Bahamas). Pharm: Cytotoxic (NCI’s 60 cell-line panel, mean IC50 = 27.4 μg/mL, HCT116, IC50 = 9.8 μg/mL, Colon205, IC50 = 3.5 μg/mL, SK-MEL-2, IC50 = 5.9 μg/mL, MAXF-401 IC50 = 0.02 μg/mL); antiviral (poxvirus Molluscum contagiosum virus (MCV), topoisomerase selective inhibitor). Ref: G. N. Belofsky, et al, Tet. Lett., 1999, 40, 2913│Y. Hwang, et al, Mol. Pharmacol., 1999, 55, 1049│Y. Lee, et al, Org. Lett., 2000, 2, 3743│T. S. Bugni, et al, NPR, 2004, 21, 143 (rev)│S. Z. Moghadamtousi, et al, Mar. Drugs, 2015, 13, 4520 (rev)

H N

HN O O

O

O

O

NH

H N O

668 Scopularide A Type: Simple cyclic depsipeptides. C36H57N5O7 Needles (Me2CO), mp 229–230 °C, [α]D25 = −38° (c = 0.5, MeOH). Source: Marine-derived fungus Scopulariopsis brevicaulis from sponge Tethya aurantium (Mediterranean Sea). Pharm: Cytotoxic (significantly inhibits growth of several tumour cell lines, including panc89, HT29 and Colo357, 10 μg/mL, InRt = 25%–50%); antibacterial (gram-positive bacteria, Bacillus subtilis and Staphylococcus lentus, inactive or weak). Ref: Z. G. Yu, et al, JNP, 2008, 71, 1052

1.14 Simple Cyclic Depsipeptides

275

H N

HN O HN

O

O

NH

O NH O

O

O

669 Scopularide B Type: Simple cyclic depsipeptides. C34H53N5O7 Amorph. powder, [α]D25 = −43° (c = 0.5, MeOH). Source: Marine-derived fungus Scopulariopsis brevicaulis from sponge Tethya aurantium (Mediterranean Sea). Pharm: Cytotoxic (significantly inhibits growth of several tumour cell lines, including Panc89, HT29 and Colo357, 10 μg/mL, InRt = 25%– 50%); antibacterial (gram-positive bacteria, Bacillus subtilis and Staphylococcus lentus. inactive or weak). Ref: Z. G. Yu, et al, JNP, 2008, 71, 1052

H N

HN O HN

O

O

NH

O NH O

O

O

670 Seragamide A Type: Simple cyclic depsipeptides. C29H42IN3O7 Amorph. solid, [α]D27 = +45.6° (c = 0.21, CHCl3). Source: Sponge Suberites japonicas (Seragaki, Okinawa, yield = 0.00029%ww). Pharm: Cytotoxic (MTT assay, NBT-T2 (BRC-1370), IC50 = 0.064 μmol/L; 0.01 μmol/L caused multinuclei formation in cells); G-actin polymerization promoter (Prodan-actin assay, seragamide A in 20–200 nmol/L facilitated polymerization of 1 μmol/L G-actin); F-actin filaments stabilizer (Prodan-actin assay, inhibits depolymerization of F-actin, 100 nmol/L). Ref: C. Tanaka, et al, Tetrahedron, 2006, 62, 3536

276

1 Peptides

OH H

O

HN I

20

O O

N

HO

O O

14

N

30

H

671 Seragamide B Type: Simple cyclic depsipeptides. C29H42BrN3O7 Amorph. solid, [α]D27 = +39° (c = 0.09, CHCl3). Source: Sponge Suberites japonicas (Seragaki, Okinawa). Pharm: Cytotoxic (MTT assay, NBT-T2 (BRC-1370), IC50 = 0.12 μmol/L; 0.02 μmol/L caused multinuclei formation in cells). Ref: C. Tanaka, et al, Tetrahedron, 2006, 62, 3536 OH H

O

HN Br

20

O O

N

HO

O O

14

N

30

H

672 Seragamide C Type: Simple cyclic depsipeptides. C29H42ClN3O7 Glass, [α]D23 = +53° (c = 0.1, CHCl3). Source: Sponge Suberites japonicas (Seragaki, Okinawa). Pharm: Cytotoxic (MTT assay, NBT-T2 (BRC-1370), IC50 = 0.10 μmol/L; 0.01 μmol/L caused multinuclei formation in cells). Ref: C. Tanaka, et al, Tetrahedron, 2006, 62, 3536 OH H

O

HN Cl 20 HO

O N

O

O O

14 30

N H

673 Seragamide D Type: Simple cyclic depsipeptides. C28H40IN3O7 Glass, [α]D23 = +46° (c = 0.07, CHCl3). Source: Sponge Suberites japonicas (Seragaki, Okinawa). Pharm: Cytotoxic (MTT assay, NBT-T2 (BRC-1370), IC50 = 0.18 μmol/L; 0.01 μmol/L caused multinuclei formation in cells). Ref: C. Tanaka, et al, Tetrahedron, 2006, 62, 3536

1.14 Simple Cyclic Depsipeptides

277

OH H

O

HN I

20

O

O O

N

HO

14

O

N H

674 Seragamide E Type: Simple cyclic depsipeptides. C29H42IN3O8 Glass, [α]D24 = +33° (c = 0.09, CHCl3). Source: Sponge Suberites japonicas (Seragaki, Okinawa). Pharm: Cytotoxic (MTT assay, NBT-T2 (BRC-1370), IC50 = 0.58 μmol/L; 0.04 μmol/L caused multinuclei formation in cells). Ref: C. Tanaka, et al, Tetrahedron, 2006, 62, 3536 OH H

O

HN I

8

20

O O

N

HO

O O

14

N

30

1

OH

675 Solomonamide A Type: Simple cyclic depsipeptides. C21H29N5O9 Source: Lithistid sponge Theonella swinhoei (Vangunu I., Solomon Is.). Pharm: Anti-inflammatory. Ref: C. Festa, et al, Org. Lett., 2011, 13, 1532 NH2

HO O

NH

HO

O O

HO

H N

OH

HN

NH O

O

676 Sulfinyltheonellapeptolide 2 Type: Simple cyclic depsipeptides. C69H123N13O16S Colorless amorphous solid, [α]D = −38.1° (c = 0.1, MeOH). Source: Lithistid sponge Theonella swinhoei

278

1 Peptides

(N. Sulawesi, Indonesia). Pharm: Cytotoxic (HepG2, IC50 = 3 μmol/L). Ref: A. Sinisi, et al, Beilstein J. Org. Chem., 2013, 9, 1643 O

O

N

N H

S

O

O H N

O

NH O

N O

HN

O

O

O NH O

N

HN

O

H N

H N

O N O

O

O

N

D-Val

677 12ʹ-Sulfoxythiocoraline Type: Simple cyclic depsipeptides. C48H56N10O13S6 White solid, [α]D25 = −96° (c = 0.0013, CHCl3). Source: Marine-derived bacterium Verrucosispora sp. from lithistid sponge Chondrilla caribensis f. caribensis (Florida Keys, USA). Pharm: Cytotoxic (A549, EC50 = 1.26 μmol/L). Ref: T. P. Wyche, et al, JOC, 2011, 76, 6542

N

OH H N O

O

O S

S

O

N

NH O

S

N O

O

N

S N

O HN S

S O

O

O

N H

N

HO

678 Symplocamide A Type: Simple cyclic depsipeptides. C46H71BrN10O13 Pale yellow solid, [α]D23 = −43.2° (c = 0.06, MeOH). Source: Cyanobacterium Symploca sp. Pharm: Anticancer-CellEffect (model: chymotrypsin, mechanism: serine protease inhibition); cytotoxic (H460); serine protease selective inhibitor (chymotripsin, IC50 = 0.38 μmol/L; trypsin, IC50 = 80.2 μmol/L, difference greater than 200-fold); cytotoxin. Ref: R. G. Linington, et al, JNP, 2008, 71, 22│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev)

1.14 Simple Cyclic Depsipeptides

O O Br

N H

O

O

N

O

O N

O

HN

H N

NH2 O

H N

O

N H

O H N

NH2 O

O

HO

279

679 Tamandarin A Type: Simple cyclic depsipeptides. C54H85N7O14 Amorph. solid, [α]D = −35° (c = 0.11, MeOH). Source: Ascidian Didemnum sp. (Brazil). Pharm: Cytotoxic (pancreatic carcinoma, in vitro, ED50 = 1.5–2.0 ng/mL). Ref: B. Liang, et al, Org. Lett., 1999, 1, 1319│H. Vervoort, et al, JOC, 2000, 65, 782│B. Liang, et al, JACS, 2001, 123, 4469 OH

OH

O

O

N

O N

O

O O

O N H

HN

NH O

O N

O

O N

O

680 Tamandarin B Type: Simple cyclic depsipeptides. C53H83N7O14 Amorph. solid, [α]D = −29° (c = 0.11, MeOH). Source: Ascidian Didemnum sp. (Brazil). Pharm: Cytotoxic (NCI-60 tumor cell screen, mean GI50 = 2.3 nmol/L, mean LC50 = 1.4 μmol/L). Ref: H. Vervoort, et al, JOC, 2000, 65, 782│M. M. Joullié, et al, Tet. Lett., 2000, 41, 9373│B. Liang, et al, JACS, 2001, 123, 4469

280

1 Peptides

OH O

OH O

N

O

O

O O

N

HN

NH

O

O

O

N H

O

O N

N

O

681 Tausalarin C Type: Simple cyclic depsipeptides. C66H95N5O19 Pale yellow oil, [α]D24 = −6° (c = 0.64, CHCl3). Source: Sponge Fascaplysinopsis sp. (Salary Bay, Madagascar). Pharm: Cytotoxic (K562, 1 μmol/L, inhibits cell growth 35%, 65%, and 74% after 24 h, 48 h, and 72 h, respectively; UT7, inactive). Ref: A. Bishara, et al, Org. Lett., 2009, 11, 3538

H N O

O

OO O

NH O

O

O

N

O O

HO O O

O N H

O O

O

O N O

682 Tetrahydroveraguamide A Type: Simple cyclic depsipeptides. C37H63BrN4O8 Colorless amorphous solid, [α]D20 = −43° (c = 0.05, MeOH). Source: Cyanobacterium Symploca cf. hydnoides (Cetti Bay, Guam). Pharm: Cytotoxic (HT29, IC50 = 33 μmol/L, control Paclitaxel, IC50 = 0.003 μmol/L; HeLa, IC50 = 48 μmol/L, Paclitaxel, IC50 = 0.0026 μmol/L). Ref: L. A. Salvador, et al, JNP, 2011, 74, 917

1.14 Simple Cyclic Depsipeptides

O

281

N O O

O

N

HN O

O

O

Br

N

O

683 Theonellapeptolide Ia Type: Simple cyclic depsipeptides. C69H123N13O16 Needles (MeOH aq), mp 156–157 °C, [α]D20 = −58° (c = 1.4, MeOH). Source: Lithistid sponge Theonella swinhoei. Pharm: Immunosuppressive; NaK-ATPase inhibitor; ionophoric agent. Ref: M. C. Roy, et al, Tennen Yuki Kagobutsu Toronkai Koen Yoshishu, 2000, 42, 355 O HN

O O

H N

N MLeu O

O

W=beta-Ala

O

Thr

N H

N H

N Leu

O

O

X=MeIle

O

O Z MeIle

NH beta-Ala

N

O

HN

Leu

O

NH O

H N beta-Ala

O

N

O Y=Val

O N MeVal

10MeAla

684 Theonellapeptolide Ib Type: Simple cyclic depsipeptides. C69H123N13O16 Needles (MeOH aq), mp 159 °C, [α]D20 = −54° (c = 1.8, MeOH). Source: Lithistid sponge Theonella swinhoei. Pharm: Na/K-ATPase inhibitor; ionophoric agent. Ref: I. Kitagawa, et al, Tetrahedron, 1991, 47, 2169

282

O

1 Peptides

H N

O

H N

N MLeu O

O

O

W=beta-Ala

O

Thr

N H

N H

N Leu

X=MeVal

O

O

O

O

NH beta-Ala

ZMeIle

N

O O

NH H N

O

O

HN

Leu

O N

N

MeVal

beta-Ala

O

Y=Ile

10MeAla

685 Theonellapeptolide Ic Type: Simple cyclic depsipeptides. C69H123N13O16 Needles (MeOH aq), mp 147 °C, [α]D20 = −50° (c = 1.1, MeOH). Source: Lithistid sponge Theonella swinhoei. Pharm: Na/K-ATPase inhibitor; ionophoric agent. Ref: I. Kitagawa, et al, Tetrahedron, 1991, 47, 2169

O

H N O

O

H N

N MLeu O

O

W=beta-Ala

O

Thr

N H

N H

N Leu

X=MeIle

O

O

NH

beta-Ala

O Z=MeVal

O

N

O Leu

O

NH

O

O

HN

H N beta-Ala

O

N

Y=Ile

O N MeVal

10MeAla

686 Theonellapeptolide Id Type: Simple cyclic depsipeptides. C70H125N13O16 Needles (MeOH aq), mp 168–169 °C, [α]D20 = −68° (MeOH). Source: Lithistid sponges Theonella swinhoei (N. Sulawesi, Indonesia) and Theonella sp. (Okinawa). Pharm: Immunosuppressive; cytotoxic (L1210, IC50 = 2.4 μg/mL); cytotoxic (HepG2, IC50 = 1.5 μmol/L). Ref: M. Kobayashi, et al, CPB, 1991, 39, 1177│M. C. Roy, et al, Tennen Yuki Kagobutsu Toronkai Koen Yoshishu, 2000, 42, 355; CA, 134, 323642│A. Sinisi, et al, Beilstein J. Org. Chem., 2013, 9, 1643

1.14 Simple Cyclic Depsipeptides

O

H N

O

H N

N MLeu O

O

O

W=beta-Ala

283

O

Thr

N H

N

N H

Leu

X=MeIle

O

O

O

O

NH beta-Ala

Z=MeIle

N

O Leu

O

NH H N

O

O

HN

O

N

N

beta-Ala

Y=Ile

O

MeVal

10MeAla

687 Theonellapeptolide Ie Type: Simple cyclic depsipeptides. C71H127N13O16 Cryst. (MeOH), mp 153–155 °C, [α]D20 = −62° (c = 0.2, MeOH). Source: Lithistid sponge Theonella swinhoei. Pharm: Na/K-ATPase inhibitor; ionophoric agent. Ref: I. Kitagawa, et al, Tetrahedron, 1991, 47, 2169

O

H N O

O

H N

N MLeu O

O

O Thr

N

N H

N Leu

W=beta-MeAla

X=MeIle

O

O

O

O Z=MeIle

NH beta-Ala

N

O Leu

O

NH O

O

HN

H N beta-Ala

O

N

Y=Ile

O N MeVal

10MeAla

688 Theonellapeptolide If Type: Simple cyclic depsipeptides. C68H121N13O16 Colorless amorphous solid, [α]D = −26.7° (c = 1.0, MeOH). Source: Lithistid sponge Theonella swinhoei (N. Sulawesi, Indonesia). Pharm: Cytotoxic (HepG2, IC50 = 3 μmol/L). Ref: A. Sinisi, et al, Beilstein J. Org. Chem., 2013, 9, 1643

284

1 Peptides

O N

N H

O

D-MeVal

O

O H N

O

NH O

N O

HN

O

O

O NH O

N

HN

O

H N

H N

O N

N O

O

O

D-Val

689 Theonellapeptolide IId Type: Simple cyclic depsipeptides. C69H123N13O16 Amorph. solid, [α]D = −27° (c = 1, MeOH). Source: Lithistid sponge Theonella swinhoei (Okinawa). Pharm: Immunosuppressive; prevents fertilization of sea urchin eggs. Ref: M. Kobayashi, et al, CPB, 1994, 42, 1410│M. C. Roy, et al, Tennen Yuki Kagobutsu Toronkai Koen Yoshishu, 2000, 42, 355

O

H N O

O

H N

N MLeu O

Thr

O W=beta-Ala O N H

N H

N

Leu

O

O

O Z=MeIle

X=MeIle

O

NH

beta-Ala

N

O

HN

Leu

O

NH O

beta-Ala

H N O

HN 10

O

Y=Ile

O N MeVal

10Ala

690 Theopapuamide A Type: Simple cyclic depsipeptides. C69H123N17O23 Off–white amorph. solid, [α]D23 = +6.4° (c = 0.2, MeOH), [α]D25 = −3° (c = 0.86, MeOH). Source: Lithistid sponges Theonella swinhoei (off Milne Bay, Papua New Guinea) and Siliquariaspongia mirabilis. Pharm: Cytotoxic (CEM-TART (T-cells that express both HIV-1 tat and rev), IC50 = 0.5 μmol/L, HCT116, IC50 = 0.9 μmol/L); antifungal (Candida albicans, wild type and ABRCA strains, 1 μg/disk, IZD = 8 mm). Ref: A. S. Ratnayake, et al, JNP, 2006, 69, 1582│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)│CRC Press, DNP on DVD, 2012, version 20.2

1.14 Simple Cyclic Depsipeptides

285

NH2

H

O

HO OH HO 5''

OH

3'

H 2N

O

NH

O

O

O

H2N N

O O

N H

H

O

NH2 HN

O

H N

H N

N H

O

O

O

HN

O

NH2 O

H N

N

HN

O H

O O

OH

O

NH2

691 Theopapuamide B Type: Simple cyclic depsipeptides. C71H125N17O24 Amorph. powder, [α]D23 = +7.1° (c = 0.1, MeOH). Source: Lithistid sponge Siliquariaspongia mirabilis (off Sulawesi I., Indonesia). Pharm: Cytotoxic (HCT116, IC50 = 2.5 μmol/L); cytotoxic (HCT116, IC50 = (2.1 ± 0.7)μg/mL); anti-HIV (HIV-1, IC50 = 0.5 μmol/L); anti-HIV-1 (HIV-1 SF162 envelope, neutralized HIV-1 in single-round infectivity assay, IC50 = (0.8 ± 0.3)μg/ mL); antifungal (Candida albicans, wild type and ABRCA strains, 5 μg/disk, IZD = 10 mm). Ref: A. Plaza, et al, JOC, 2009, 74, 504│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev) NH2

H

O

HO OH HO

O

5''

NH HN

O OH

3'

O HN

H N H H2N

O

O N H

O

NH

H N

N H

O

H 2N N

O

O

O O

O N

O

HN

H O

H N

NH2 O

O O

O

OH

NH2

692 Theopapuamide C Type: Simple cyclic depsipeptides. C71H125N17O23 Amorph. powder, [α]D23 = +5.1° (c = 0.08, MeOH). Source: Lithistid sponge Siliquariaspongia mirabilis (off Sulawesi I., Indonesia). Pharm: Cytotoxic (HCT116, IC50 = 1.3 μmol/L); anti-HIV (HIV-1, IC50 = 0.5 μmol/L): antifungal (Candida albicans, wild type and ABRCA strains, 5 μg/disk, IZD = 10 mm). Ref: A. Plaza, et al, JOC, 2009, 74, 504│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)

286

1 Peptides

NH2

H

O

HO OH HO O HN

HN

5''

O

3'

O

H N

O

H2N N

O

O

O

N H

H H 2N

O

NH

O

H N

N H

O

O

O

HN

O

H O

H N

N

O

HN

O NH2

O O

OH

NH2

693 Thiocoraline Antibiotic PM 93135 Type: Simple cyclic depsipeptides. C48H56N10O12S6 Pale yellow cryst., mp 266–266.5 °C, [α]D25 = −190.9° (c = 1, CHCl3). Source: Marine bacterium Micromonospora sp. L-13-ACM2-092, Marine-derived bacterium Verrucosispora sp. from lithistid sponge Chondrilla caribensis f. caribensis (Florida Keys, USA). Pharm: Cytotoxic (L1210, IC50 = 200 pmol/L, exceptionally); cytotoxic (A549, EC50 = 0.0095 μmol/L); RNA synthesis inhibitor; HIV-1 reverse transcriptase inhibitor (weak); binds to DNA (high affinity bisintercalation). Ref: F. Romero, et al, J. Antibiot., 1997, 50, 734│J.P. Baz, et al, J. Antibiot., 1997, 50, 738│D. L. Boger, et al, JACS, 2000, 122, 2956│D. L. Boger, et al, JACS, 2001, 123, 561│T. P. Wyche, et al, JOC, 2011, 76, 6542 OH

O H N

N O

O

S

S NH O

S

N O

O

N

N S

N

O HN S

S O

O

O

N H

N

HO

694 Tiglicamide A Type: Simple cyclic depsipeptides. C45H59N7O13 Amorph. solid, [α]D20 = −50° (c = 0.07, MeOH). Source: Cyanobacterium Lyngbya confervoides. Pharm: Anticancer-Cell-Effect (model: porcine pancreatic elastase, mechanism: serine protease inhibition); serine

1.14 Simple Cyclic Depsipeptides

287

protease selective inhibitor (elastase, IC50 = 2.14 μmol/L). Ref: S. Matthew, et al, Phytochemistry, 2009, 70, 2058│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev) HOOC H N

HN O O N H

H N O

O

HN

O

OO

HN O

O

N H

OH

HO

695 Tiglicamide B Type: Simple cyclic depsipeptides. C44H57N7O12 Amorph. solid, [α]D20 = −45° (c = 0.04, MeOH). Source: Cyanobacterium Lyngbya confervoides. Pharm: Anticancer-Cell-Effect (model: porcine pancreatic elastase, mechanism: serine protease inhibition); serine protease selective inhibitor (elastase, IC50 = 6.99 μmol/L). Ref: S. Matthew, et al, Phytochemistry, 2009, 70, 2058│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev) HOOC H N

HN O O N H

H N O

HN O N H

O

HN

O

OO O

HO

696 Tiglicamide C Type: Simple cyclic depsipeptides. C40H57N7O13S Amorph. solid, [α]D20 = −56° (c = 0.04, MeOH). Source: Cyanobacterium Lyngbya confervoides. Pharm: AnticancerCell-Effect (model: porcine pancreatic elastase, mechanism: serine protease inhibition); serine protease selective inhibitor (elastase, IC50 = 7.28 μmol/L). Ref: S. Matthew, et al, Phytochemistry, 2009, 70, 2058│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev)

288

1 Peptides

HOOC H N

HN O O

O

N H

O

HN

O

OO

HN O

H N

N H

O

S O

HO

697 Ulongapeptin Type: Simple cyclic depsipeptides. C44H68N6O8 Amorph. powder, [α]D21 = −16° (c = 0.4, MeOH). Source: Cyanobacterium Lyngbya sp. (Palau, Oceania). Pharm: Cytotoxic (KB, IC50 = 0.63 μmol/L). Ref: P. G. Williams, et al, JNP, 2003, 66, 651

O

H N HN

O

N O

N

O

HN O

N

O

O

O

698 Unnarmicin A Type: Simple cyclic depsipeptides. C36H50N4O6 Amorph. solid, [α]D30 = +70° (c = 0.19, MeOH). Source: Marine-derived bacterium Photobacterium sp. MBIC06485. Pharm: Antibacterial (selectively inhibits growth of two Pseudovibrio sp. strains (one of most prevalent genera in marine environments in class Alphaproteobacteria), plate diffusion assay, Pseudovibrio denitrificans JCM12308, 13 μg, IZD = 7 mm, 2.6 μg, IZD = 7 mm; Pseudovibrio sp. MBIC3368, 13 μg, IZD = 8 mm, 2.6 μg, IZD = 7 mm). Ref: K. Tanabe, et al, Biochem. Biophys. Res. Commun., 2007, 364, 990│N. Oku, et al, J. Antibiot., 2008, 61, 11

1.14 Simple Cyclic Depsipeptides

O

NH NH

O O

O

O

289

HN

O

N H

699 Unnarmicin C Type: Simple cyclic depsipeptides. C38H54N4O6 Amorph. solid Source: Marinederived bacterium Photobacterium sp. MBIC06485. Pharm: Antibacterial (selectively inhibits growth of two Pseudovibrio sp. strains (one of most prevalent genera in marine environments in class Alphaproteobacteria), plate diffusion assay, Pseudovibrio denitrificans JCM12308, 13 μg, IZD = 18 mm, 2.6 μg, IZD = 10 mm; Pseudovibrio sp. MBIC3368, 13 μg, IZD = 12 mm, 2.6 μg, IZD = 9 mm). Ref: K. Tanabe, et al, Biochem. Biophys. Res. Commun., 2007, 364, 990│N. Oku, et al, J. Antibiot., 2008, 61, 11

O

NH NH

O

O

O O

HN

O

N H

700 Veraguamide A Type: Simple cyclic depsipeptides. C37H59BrN4O8 Colorless amorphous solid, [α]D20 = −44° (c = 0.44, MeOH); amorphous solid, [α]D22 = −14.7° (c = 0.33, CH2Cl2); Source: Cyanobacteria Symploca cf. hydnoides (Cetti Bay, Guam) and Oscillatoria margaritifera (Isla Canales de Afuera, Panama). Pharm: Cytotoxic (HT29, IC50 = 26 μmol/L, control Paclitaxel, IC50 = 0.003 μmol/L; HeLa, IC50 = 21 μmol/L, Paclitaxel, IC50 = 0.0026 μmol/L); cytotoxic (H460, LD50 = 141 nmol/L). Ref: L. A. Salvador, et al, JNP, 2011, 74, 917│E. Mevers, et al, JNP, 2011, 74, 928

290

1 Peptides

O

N O O

O

N

HN O

O

O

N

Br

O

701 Veraguamide B Type: Simple cyclic depsipeptides. C36H57BrN4O8 Colorless amorphous solid, [α]D20 = −40° (c = 0.16, MeOH); amorphous solid, [α]D23 = −13.1° (c = 0.25, CH2Cl2). Source: Cyanobacteria Symploca cf. hydnoides (Cetti Bay, Guam) and Oscillatoria margaritifera (Isla Canales de Afuera, Panama). Pharm: Cytotoxic (HT29, IC50 = 30 μmol/L, control Paclitaxel, IC50 = 0.003 μmol/L; HeLa, IC50 = 17 μmol/L, Paclitaxel, IC50 = 0.0026 μmol/L). Ref: L. A. Salvador, et al, JNP, 2011, 74, 917│E. Mevers, et al, JNP, 2011, 74, 928

O

N O O

O

N

HN O N

O

O O

Br

702 Veraguamide C Type: Simple cyclic depsipeptides. C37H60N4O8 Colorless amorphous solid, [α]D20 = −44° (c = 0.31, MeOH); amorphous solid, [α]D23 = −13.0° (c = 0.17, CH2Cl2). Source: Cyanobacteria Symploca cf. hydnoides (Cetti Bay, Guam) and Oscillatoria margaritifera (Isla Canales de Afuera, Panama). Pharm: Cytotoxic (HT29, IC50 = 5.8 μmol/L, control Paclitaxel, IC50 = 0.003 μmol/L; HeLa, IC50 = 5.1 μmol/L, Paclitaxel, IC50 = 0.0026 μmol/L). Ref: L. A. Salvador, et al, JNP, 2011, 74, 917│E. Mevers, et al, JNP, 2011, 74, 928

1.14 Simple Cyclic Depsipeptides

291

N

O O

O

O

HN

N O

O

O

N

O

703 Veraguamide D Type: Simple cyclic depsipeptides. C38H62N4O8 Colorless amorphous solid, [α]D20 = −57° (c = 0.11, MeOH). Source: Cyanobacterium Symploca cf. hydnoides (Cetti Bay, Guam). Pharm: Cytotoxic (HT29, IC50 = 0.84 μmol/L, control Paclitaxel, IC50 = 0.003 μmol/L; HeLa, IC50 = 0.54 μmol/L, Paclitaxel, IC50 = 0.0026 μmol/L). Ref: L. A. Salvador, et al, JNP, 2011, 74, 917 N

O

O

N O

O O

O

O

H N

O

N

704 Veraguamide E Type: Simple cyclic depsipeptides. C39H64N4O8 Colorless amorphous solid, [α]D20 = −56° (c = 0.22, MeOH). Source: Cyanobacterium Symploca cf. hydnoides (Cetti Bay, Guam). Pharm: Cytotoxic (HT29, IC50 = 1.5 μmol/L, control Paclitaxel, IC50 = 0.003 μmol/L; HeLa, IC50 = 0.83 μmol/L, Paclitaxel, IC50 = 0.0026 μmol/L). Ref: L. A. Salvador, et al, JNP, 2011, 74, 917 N

O

O

N O

O O

O

H N

O N

O

292

1 Peptides

705 Veraguamide F Type: Simple cyclic depsipeptides. C41H60N4O8 Colorless amorphous solid, [α]D20 = −41° (c = 0.13, MeOH). Source: Cyanobacterium Symploca cf. hydnoides (Cetti Bay, Guam). Pharm: Cytotoxic (HT29, IC50 = 49 μmol/L, control Paclitaxel, IC50 = 0.003 μmol/L; HeLa, IC50 = 49 μmol/L, Paclitaxel, IC50 = 0.0026 μmol/L). Ref: L. A. Salvador, et al, JNP, 2011, 74, 917

N O

O

O

N O

O O

O

H N

O

N

706 Veraguamide G Type: Simple cyclic depsipeptides. C37H62N4O8 Colorless amorphous solid, [α]D20 = −48° (c = 0.17, MeOH). Source: Cyanobacterium Symploca cf. hydnoides (Cetti Bay, Guam). Pharm: Cytotoxic (HT29, IC50 = 2.7 μmol/L, control Paclitaxel, IC50 = 0.003 μmol/L; HeLa, IC50 = 2.3 μmol/L, Paclitaxel, IC50 = 0.0026 μmol/L). Ref: L. A. Salvador, et al, JNP, 2011, 74, 917

N

O

O

O

H N

N O O O

O

O

N

707 Viequeamide A Type: Simple cyclic depsipeptides. C42H69N5O10 Source: Cyanobacterium Rivularia sp. (Playa de la Chiva, Vieques I., Puerto Rico). Pharm: Cytotoxic (H460, high toxic). Ref: P. D. Boudreau, et al, JNP, 2012, 75, 1560

1.14 Simple Cyclic Depsipeptides

293

N O

O N

O O N

O

O

O

NH

NH

O HO

O

708 Wewakamide A Type: Simple cyclic depsipeptides. C53H86N8O10 Source: Cyanobacterium Lyngbya semiplena (Wewak Bay, Papua New Guinea). Pharm: Toxic (brine shrimp, potent). Ref: B. Han, et al, J. Microbiol. Biotechnol., 2011, 21, 930

O

H N O

HN

O

O N H

N

O

O

N

O O N H

O N

O N

709 Wewakpeptin A Type: Simple cyclic depsipeptides. C52H85N7O11 Amorph. solid, [α]D26 = −45° (c = 0.4, CHCl3). Source: Cyanobacterium Lyngbya semiplena (Papua New Guinea). Pharm: Cytotoxic (NCI-H460, LC50 = 0.49 μmol/L; neuro-2a, LC50 = 0.65 μmol/L). Ref: B. Han, et al, JOC, 2005, 70, 3133

294

1 Peptides

O

N

N O

O

N

O

O

O N

O

N

O

H N

O

H

NH O

O 8

7

710 Wewakpeptin B Type: Simple cyclic depsipeptides. C52H89N7O11 Amorph. solid, [α]D26 = −53° (c = 0.47, CHCl3). Source: Cyanobacterium Lyngbya semiplena (Papua New Guinea). Pharm: Cytotoxic (NCI-H460, LC50 = 0.20 μmol/L; neuro-2a, LC50 = 0.43 μmol/L). Ref: B. Han, et al, JOC, 2005, 70, 3133

O

N

N O

O

N

O

O

O N

N

O O

H N

O

H

NH O

8

O

7

711 Wewakpeptin C Type: Simple cyclic depsipeptides. C54H81N7O11 Amorph. solid, [α]D26 = −56° (c = 0.27, CHCl3). Source: Cyanobacterium Lyngbya semiplena (Papua New Guinea). Pharm: Cytotoxic (NCI-H460, LC50 = 10.7 μmol/L; neuro-2a, LC50 = 5.9 μmol/L). Ref: B. Han, et al, JOC, 2005, 70, 3133

1.14 Simple Cyclic Depsipeptides

295

O

N

N O

O

N

O

O

O N

N

O O

H N

O

H

NH O

O 8

7

712 Wewakpeptin D Type: Simple cyclic depsipeptides. C54H85N7O11 Amorph. solid, [α]D26 = −65° (c = 0.6, CHCl3). Source: Cyanobacterium Lyngbya semiplena (Papua New Guinea). Pharm: Cytotoxic (NCI-H460, LC50 = 1.9 μmol/L; neuro-2a, LC50 = 3.5 μmol/L). Ref: B. Han, et al, JOC, 2005, 70, 3133

O

N

N O

O

N

O

O

O N

N

O O

H N

O

H

NH O

8

O

7

713 Yanucamide A Type: Simple cyclic depsipeptides. C33H47N3O7 Colorless amorphous solid, [α]D25 = −33° (c = 0.1, MeOH). Source: Cyanobacteria Lyngbya majuscula and Schizothrix sp. (assemblage, Fiji). Pharm: Toxic (brine shrimp, strong). Ref: N. Sitachitta, et al, JNP, 2000, 63, 197

296

1 Peptides

H N O

N O

O O

O

O

N H

O

H

714 Yanucamide B Type: Simple cyclic depsipeptides. C34H49N3O7 Colorless amorphous solid, [α]D25 = −31° (c = 0.1, MeOH). Source: Cyanobacteria Lyngbya majuscula and Schizothrix sp. (assemblage, Fiji). Pharm: Toxic (brine shrimp, strong). Ref: N. Sitachitta, et al, JNP, 2000, 63, 197

H N O

N O

O O

O

O

N H

O

H

715 Zygosporamide Type: Simple cyclic depsipeptides. C36H50N4O6 Powder, [α]D20 = −112° (c = 0.26, MeCN). Source: Marine-derived fungus Zygosporium masonii from an unidentified cyanobacterium (off Maui, Hawaii). Pharm: Cytotoxic (NCI’s 60 cell line panel, median GI50 = 9.1 μmol/L; SF268, GI50 = 6.5 nmol/L, high selective; RXF-393, GI50 = 5.0 nmol/L, high selective). Ref: D. -C. Oh, et al, Tet. Lett., 2006, 47, 8625

O

O

NH

O

O

N H O

HN H N O

1.15 Cyclic Lipodepsipeptides

297

1.15 Cyclic Lipodepsipeptides 716 Antillatoxin Type: Cyclic lipodepsipeptides. C28H45N3O5 Colorless oil, [α]D = −140° (Nat., c = 0.13, MeOH), [α]D = −147° (Syn., c = 0.23, MeOH). Source: Cyanobacterium Lyngbya majuscula (Curaçao). Pharm: Anticancer-Cell-Effect (model: primary rat cerebellar granule cells, mechanism: voltage-gated Sodium channel VGSC) (Li, 2001); anticancer-CellEffect (model: CHL-1610, mechanism: Sodium channel activation) (Cao, 2010); ichthyotoxin; neurotoxin; toxin (most ichthyotoxic metabolites isolated to date from a marine plant; LD50 (goldfish) = 0.005 or 0.05 μg/mL). Ref: J. Orjala, et al, JACS, 1995, 117, 8281│J. D. White, et al, JACS, 1999, 121, 1106│E Yokokawa, et al, Tet. Lett., 1999, 40, 1915│F. Yokokawa, et al, Tetrahedron, 2000, 56, 1759│W. I. Li, Proc. Natl. Acad. Sci. USA, 2001, 98, 7599│W. I. Li, et al, JNP, 2004, 67, 559│K. Okura, et al, Angew. Chem., Int. Ed., 2010, 49, 329│H. Choi, et al, JNP, 2010, 73, 1411 O O

N H H N

N O

5R

O

4R

O

717 Antillatoxin B Type: Cyclic lipodepsipeptides. C33H47N3O5 Oil, [α]D23 = −113.8° (c = 0.21, MeOH). Source: Cyanobacterium Lyngbya majuscula (Puerto Rico and Dry Tortugas National Park, Florida). Pharm: Anticancer-Cell-Effect (model: neuro-2a, mechanism: Sodium channel activation); ichthyotoxin; neurotoxin. Ref: L. M. Nogle, et al, JNP, 2001, 64, 983

O

N O

O

N H H N

O

5R 4R

O

718 Arenamide A Type: Cyclic lipodepsipeptides. C36H57N5O7 Cryst., mp 225 °C, [α]D25 = −76.3° (c = 0.08, MeOH). Source: Marine-derived bacterium Salinispora arenicola CNT-088. Pharm: NFκB inhibitor (blocked TNF-induced NF-κB activation in dose- and timedependent manner with IC50 = 3.7 μmol/L); inhibits NO and PGE2 production (LPSinduced RAW 264.7); cytotoxic (HCT116, IC50 = 13.2 μg/mL; cultured RAW cells,

298

1 Peptides

inactive); anti-inflammatory and chemoprevention. Ref: R. N. Asolkar, et al, JNP, 2009, 72, 396 O

H N O

O

O

N H

HN

O

O

NH HN O

719 Arenamide B Type: Cyclic lipodepsipeptides. C34H53N5O7 Cryst., mp 232 °C, [α]D25 = −96.3° (c = 0.27, MeOH). Source: Marine-derived bacterium Salinispora arenicola CNT-088. Pharm: NFκB inhibitor (blocked TNF-induced NF-κB activation in dose- and timedependent manner with IC50 = 1.7 μmol/L); inhibits NO and PGE2 production (LPSinduced RAW 264.7); cytotoxic (HCT116, IC50 = 19.2 μg/mL; cultured RAW cells, inactive); anti-inflammatory and chemoprevention. Ref: R. N. Asolkar, et al, JNP, 2009, 72, 396 O

H N O

O

O

N H

HN

O

O

NH HN O

720 Arenamide C Type: Cyclic lipodepsipeptides. C32H57N5O7S Powder, [α]D25 = −45° (c = 0.09, MeOH). Source: Marine-derived bacterium Salinispora arenicola CNT-088 (sediment, Great Astrolabe Reef, Fiji). Pharm: NF-κB inhibitor; cytotoxic. Ref: R. N. Asolkar, et al, JNP, 2009, 72, 396; 2010, 73, 796 O

H N

S O

O

O

N H O N H

HN H N O

O

1.15 Cyclic Lipodepsipeptides

299

721 Bacillus pumilus KMM 1364 Lipodepsipeptide A Type: Cyclic lipodepsipeptides. C53H93N7O13 Source: Marine-derived bacterium Bacillus pumilus KMM 1364 from ascidian Halocynthia aurantium. Pharm: Surfactant. Ref: N. I. Kalinovskaya, et al, Mar. Biotechnol., 2002, 4, 179 HO

O H N

H N

O

O

O

HN O

O

O

NH

O

O

HN N H

N H

O

O HO

722 Bacillus pumilus KMM 1364 Lipodepsipeptide B Type: Cyclic lipodepsipeptides. C53H93N7O13 Source: Marine-derived bacterium Bacillus pumilus KMM 1364 from ascidian Halocynthia aurantium. Pharm: Surfactant. Ref: N. I. Kalinovskaya, et al, Mar. Biotechnol., 2002, 4, 179 HO O

H N

H N

O

O

O O

HN O

O NH O

O

HN N H

N H

O

O HO

723 Bacillus pumilus KMM 1364 Lipodepsipeptide C Type: Cyclic lipodepsipeptides. C54H95N7O13 Source: Marine-derived bacterium Bacillus pumilus KMM 1364 from ascidian Halocynthia aurantium. Pharm: Surfactant. Ref: N. I. Kalinovskaya, et al, Mar. Biotechnol., 2002, 4, 179

300

1 Peptides

HO O

H N

H N

O

O

O O

HN O

O NH

HN

O

O

O

N H

N H

O HO

724 Bacillus pumilus KMM 1364 Lipodepsipeptide D Type: Cyclic lipodepsipeptides. C54H95N7O13 Source: Marine-derived bacterium Bacillus pumilus KMM 1364 from ascidian Halocynthia aurantium. Pharm: Surfactant. Ref: N. I. Kalinovskaya, et al, Mar. Biotechnol., 2002, 4, 179 HO O

H N

H N

O

O

O O

HN O

O NH O

O

HN N H

N H

O

O HO

725 Bacillus pumilus KMM 1364 Lipodepsipeptide E Type: Cyclic lipodepsipeptides. C55H97N7O13 Source: Marine-derived bacterium Bacillus pumilus KMM 1364 from ascidian Halocynthia aurantium. Pharm: Surfactant. Ref: N. I. Kalinovskaya, et al, Mar. Biotechnol., 2002, 4, 179

1.15 Cyclic Lipodepsipeptides

301

HO O

H N

H N

O

O

O O

HN O

O NH O

HN

O

O

N H

N H

O HO

726 Bacillus pumilus KMM 1364 Lipodepsipeptide F Type: Cyclic lipodepsipeptides. C56H99N7O13 Source: Marine-derived bacterium Bacillus pumilus KMM 1364 from ascidian Halocynthia aurantium. Pharm: Surfactant. Ref: N. I. Kalinovskaya, et al, Mar. Biotechnol., 2002, 4, 179 HO O

H N

H N

O

O

O O

HN O

O NH O

O

HN N H

N H

O

O HO

727 Bacillus pumilus KMM 1364 Lipodepsipeptide G Type: Cyclic lipodepsipeptides. C56H99N7O13 Source: Marine-derived bacterium Bacillus pumilus KMM 1364 from ascidian Halocynthia aurantium. Pharm: Surfactant. Ref: N. I. Kalinovskaya, et al, Mar. Biotechnol., 2002, 4, 179

302

1 Peptides

HO O

H N

O

H N

O

O O

HN O

O NH O

HN

O

N H

N H

O

O HO

728 Dolastatin 14 Type: Cyclic lipodepsipeptides. C59H92N8O11 Amorph., mp 123–125 °C, [α]D24 = −146° (c = 0.14, MeOH). Source: Cyanobacterium Symploca laeteviridis, sea hare Dolabella auricularia. Pharm: Cytotoxic (NCI PS system P388 cells, ED50 = 0.022 μg/mL). Ref: G. R. Pettit, et al, JOC, 1990, 55, 2989│G. R. Pettit, et al, Tetrahedron, 1993, 49, 9151 O

O

N

N

N O

O

O

O O

NH2

N

N O

O N O

N H

O

729 Halobacillin Type: Cyclic lipodepsipeptides. C53H94N8O12 Non–cryst. solid, [α]D = −10.6° (c = 2.8, MeOH). Source: Marine bacterium Bacillus sp. CND-914 (from sediment core, Gulf of California). Pharm: Cytotoxic (HCT116, IC50 = 0.98 μg/mL). Ref: J. A. Trischman, et al, Tet. Lett., 1994, 35, 5571

1.15 Cyclic Lipodepsipeptides

303

H2N O

H N

H N

O

O HN

O O

O

O H

HN O

NH O

O

N H

N H

COOH

730 Hassallidin A Type: Cyclic lipodepsipeptides. C62H99N11O24 Amorph. solid. Source: Cyanobacterium Hassallia sp. Pharm: Antifungal (all tested Candida spp. (22 samples) and Cryptococcus neoformansisolates (7 samples), MIC = 4–8 μg/mL, independently from the species). Ref: T. Neuhof, et al, JNP, 2005, 68, 695│T. Neuhof, et al, Biochem. Biophys. Res. Commun., 2006, 349, 740 NH2

O NH2

O

O

N

HN O HN

N H

O O

O O

O

HO

OH

O

O

OH

HO OH H N

O

O

N H

O NH

N H HO

OH

H N

39

O

OH

OH

731 Homophymine A Type: Cyclic lipodepsipeptides. C73H127N15O24 [α]D = +9.3° (c = 0.48, MeOH). Source: Lithistid sponge Homophymia sp. (shallow waters off east coast of New Caledonia). Pharm: Anti-HIVs (assay with PBMC cells infected by HIV-1 III B strain); cytoprotective agent (infection production inhibitor, IC50 = 75 nmol/L); cytotoxic (uninfected PBMC cells, IC50 = 1.19 μmol/L; infected PBMC cells, almost sixteen times more effective); cytotoxic (KB, IC50 = 7.3 nmol/L; MCF7, IC50 = 23.6 nmol/L; resistant MCF7, IC50 = 22.9 nmol/L; HCT116, IC50 = 6.0 nmol/L; HCT15, IC50 = 22.5 nmol/L; HT29, IC50 = 70.0 nmol/L; OVCAR-8, IC50 = 5.4 nmol/L; SK-OV-3, IC50 = 7.5 nmol/L; PC3,

304

1 Peptides

IC50 = 4.2 nmol/L; Vero, IC50 = 5.0 nmol/L; MRC-5, IC50 = 11.0 nmol/L; HL60, IC50 = 24.1 nmol/L, antiproliferative; resistant HL60, IC50 = 22.4 nmol/L; K562, IC50 = 24.0 nmol/L; MiaPaCa, IC50 = 31.4 nmol/L; SF268, IC50 = 9.9 nmol/L; A549, IC50 = 8.3 nmol/L; MDA231, IC50 = 10.9 nmol/L; MDA435, IC50 = 39.0 nmol/L; HepG2, IC50 = 68.6 nmol/L; EPC, IC50 = 5.0 nmol/L) (Zampella, 2008); cytotoxic (a panel of cell lines including hmn cancer, Vero cell lines, IC50 = 2 nmol/ L–100 nmol/L, special potent for PC3 and SK-OV-3; further studies were found to undergo apoptosis through a caspase independent pathway). Ref: A. Zampella, et al, JOC, 2008, 73, 5319│A. E. Wright, Current Opinion in Biotechnology 2010, 21, 801│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev) O

O O

OH

HO

NH

O

NH2

OH

N H

O

HN O OH

N

NH2 HOOC

OH

O

H N

O

N H

O O

O

O

O

H N

NH2

HN

N

H N O

O

NH

O

O NH2

732 Homophymine A1 Type: Cyclic lipodepsipeptides. C73H128N16O23 Amorph. solid, [α]D = +5.2° (c = 0.96, MeOH). Source: Lithistid sponge Homophymia sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 7.1 nmol/L; MCF7, IC50 = 12.4 nmol/L; resistant MCF7, IC50 = 13.5 nmol/L; HCT116, IC50 = 6.1 nmol/L; HCT15, IC50 = 13.5 nmol/L; HT29, IC50 = 30.9 nmol/L; OVCAR-8, IC50 = 5.1 nmol/L; SK-OV-3, IC50 = 5.5 nmol/L; PC3, IC50 = 3.7 nmol/L; Vero, IC50 = 6.1 nmol/L; normal MRC-5, IC50 = 7.8 nmol/L; HL60, IC50 = 17.3 nmol/L, antiproliferative; resistant HL60, IC50 = 11.1 nmol/L; K562, IC50 = 12.8 nmol/L; MiaPaCa, IC50 = 19.2 nmol/L; SF268, IC50 = 6.3 nmol/L; A549, IC50 = 6.0 nmol/L; MDA231, IC50 = 8.4 nmol/L; MDA435, IC50 = 27.0 nmol/L; HepG2, IC50 = 91.4 nmol/L; EPC, IC50 = 7.8 nmol/L). Ref: A. Zampella, et al, Org. Biomol. Chem., 2009, 7, 4037

1.15 Cyclic Lipodepsipeptides

O

O

NH

O

NH2

O

OH

H 2N

OH

O

N

NH2

NH2

HN

O

O

O

O

H N

HOOC

OH

O

N H

O

HN O

OH

O

H N

N H

305

NH

N

H N O

O

O

O NH2

733 Homophymine B Type: Cyclic lipodepsipeptides. C72H125N15O24 Amorph. solid, [α]D = −1.3° (c = 0.57, MeOH). Source: Lithistid sponge Homophymia sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 18.0 nmol/L; MCF7, IC50 = 16.8 nmol/L; resistant MCF7, IC50 = 26.3 nmol/L; HCT116, IC50 = 13.8 nmol/L; HCT15, IC50 = 22.9 nmol/L; HT29, IC50 = 101.9 nmol/L; OVCAR-8, IC50 = 8.0 nmol/L; SK-OV-3, IC50 = 9.9 nmol/L; PC3, IC50 = 6.2 nmol/L; Vero, IC50 = 8.6 nmol/L; normal MRC-5, IC50 = 17.1 nmol/L; HL60, IC50 = 43.1 nmol/L, antiproliferative; resistant HL60, IC50 = 36.7 nmol/L; K562, IC50 = 26.7 nmol/L; MiaPaCa, IC50 = 62.0 nmol/L; SF268, IC50 = 17.2 nmol/L; A549, IC50 = 19.8 nmol/L; MDA231, IC50 = 17.0 nmol/L; MDA435, IC50 = 40.1 nmol/L; HepG2, IC50 = 99.0 nmol/L; EPC, IC50 = 8.0 nmol/L). Ref: A. Zampella, et al, Org. Biomol. Chem., 2009, 7, 4037 NH2

O

O O

OH

HO

NH

O

OH

N H

O

HN O OH

N

NH2 HOOC

OH

O

H N

O

N H

O O

O

O

O

H N

NH2

HN

N

H N O

O

NH

O

O NH2

306

1 Peptides

734 Homophymine B1 Type: Cyclic lipodepsipeptides. C72H126N16O23 Amorph. solid, [α]D = −1.5° (c = 0.5, MeOH). Source: Lithistid sponge Homophymia sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 16.4 nmol/L; MCF7, IC50 = 14.2 nmol/L; resistant MCF7, IC50 = 12.3 nmol/L; HCT116, IC50 = 11.4 nmol/L; HCT15, IC50 = 14.1 nmol/L; HT29, IC50 = 93.8 nmol/L; OVCAR-8, IC50 = 6.5 nmol/L; SK-OV-3, IC50 = 8.0 nmol/L; PC3, IC50 = 4.7 nmol/L; Vero, IC50 = 6.1 nmol/L; normal MRC-5, IC50 = 10.2 nmol/L; HL60, IC50 = 18.7 nmol/L, antiproliferative; resistant HL60, IC50 = 25.8 nmol/L; K562, IC50 = 16.6 nmol/L; MiaPaCa, IC50 = 22.2 nmol/L; SF268, IC50 = 11.7 nmol/L; A549, IC50 = 8.6 nmol/L; MDA231, IC50 = 18.2 nmol/L; MDA435, IC50 = 29.5 nmol/L; HepG2, IC50 = 100.3 nmol/L; EPC, IC50 = 6.6 nmol/L). Ref: A. Zampella, et al, Org. Biomol. Chem., 2009, 7, 4037 NH2

O

O O

OH

H 2N

NH

O

OH

N H

H N O

HN O OH

N

NH2 HOOC

OH

O

O

N H

O O

O

O

O

H N

NH2

HN

N

H N O

O

NH

O

O NH2

735 Homophymine C Type: Cyclic lipodepsipeptides. C74H129N15O24 Amorph. solid, [α]D = +5.7° (c = 0.45, MeOH). Source: Lithistid sponge Homophymia sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 8.5 nmol/L; MCF7, IC50 = 8.8 nmol/L; resistant MCF7, IC50 = 10.8 nmol/L; HCT116, IC50 = 4.9 nmol/L; HCT15, IC50 = 19.2 nmol/L; HT29, IC50 = 62.8 nmol/L; OVCAR-8, IC50 = 4.3 nmol/L; SK-OV-3, IC50 = 3.7 nmol/L; PC3, IC50 = 3.0 nmol/L; Vero, IC50 = 4.2 nmol/L; normal MRC-5, IC50 = 16.8 nmol/L; HL60, IC50 = 23.0 nmol/L, antiproliferative; resistant HL60, IC50 = 23.5 nmol/L; K562, IC50 = 22.5 nmol/L; MiaPaCa, IC50 = 25.9 nmol/L; SF268, IC50 = 13.6 nmol/L; A549, IC50 = 8.3 nmol/L; MDA231, IC50 = 16.2 nmol/L; MDA435, IC50 = 35.0 nmol/L; HepG2, IC50 = 72.1 nmol/L; EPC, IC50 = 9.3 nmol/L). Ref: A. Zampella, et al, Org. Biomol. Chem., 2009, 7, 4037

1.15 Cyclic Lipodepsipeptides

NH2

O

O O

OH

HO

NH

O

OH

O

N

NH2

NH2

HN

O

O

O

O

H N

HOOC

OH

O

N H

O

HN O

OH

O

H N

N H

307

NH

N

H N O

O

O

O NH2

736 Homophymine C1 Type: Cyclic lipodepsipeptides. C74H130N16O23 Amorph. solid, [α]D = +4.7° (c = 0.31, MeOH). Source: Lithistid sponge Homophymia sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 6.8 nmol/L; MCF7, IC50 = 6.3 nmol/L; resistant MCF7, IC50 = 5.4 nmol/L; HCT116, IC50 = 2.7 nmol/L; HCT15, IC50 = 17.2 nmol/L; HT29, IC50 = 38.2 nmol/L; OVCAR-8, IC50 = 2.6 nmol/L; SK-OV-3, IC50 = 2.4 nmol/L; PC3, IC50 = 2.6 nmol/L; Vero, IC50 = 3.1 nmol/L; normal MRC-5, IC50 = 8.0 nmol/L; HL60, IC50 = 14.6 nmol/L, antiproliferative; resistant HL60, IC50 = 17.1 nmol/L; K562, IC50 = 11.9 nmol/L; MiaPaCa, IC50 = 14.4 nmol/L; SF268, IC50 = 7.1 nmol/L; A549, IC50 = 6.2 nmol/L; MDA231, IC50 = 15.8 nmol/L; MDA435, IC50 = 20.3 nmol/L; HepG2, IC50 = 58.6 nmol/L; EPC, IC50 = 12.2 nmol/L). Ref: A. Zampella, et al, Org. Biomol. Chem., 2009, 7, 4037 NH2

O

O H 2N

O

OH

NH

O

OH

N H

O

HN O OH

N

NH2 HOOC

OH

O

H N

O

N H

O O

O

O

O

H N

NH2

HN

N

H N O

O

NH

O

O NH2

308

1 Peptides

737 Homophymine D Type: Cyclic lipodepsipeptides. C75H131N15O24 Amorph. solid, [α]D = +4.2° (c = 0.36, MeOH). Source: Lithistid sponge Homophymia sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 12.7 nmol/L; MCF7, IC50 = 19.6 nmol/L; Resistant MCF7, IC50 = 37.7 nmol/L; HCT116, IC50 = 19.8 nmol/L; HCT15, IC50 = 43.2 nmol/L; HT29, IC50 = 81.3 nmol/L; OVCAR-8, IC50 = 8.1 nmol/L; SK-OV-3, IC50 = 10.6 nmol/L; PC3, IC50 = 6.3 nmol/L; Vero, IC50 = 10.9 nmol/L; normal MRC-5, IC50 = 16.9 nmol/L; HL60, IC50 = 29.6 nmol/L; resistant HL60, IC50 = 24.9 nmol/L, antiproliferative; K562, IC50 = 35.3 nmol/L; MiaPaCa, IC50 = 37.4 nmol/L; SF268, IC50 = 17.9 nmol/L; A549, IC50 = 13.8 nmol/L; MDA231, IC50 = 18.9 nmol/L; MDA435, IC50 = 49.9 nmol/L; HepG2, IC50 = 78.7 nmol/L; EPC, IC50 = 11.1 nmol/L). Ref: A. Zampella, et al, Org. Biomol. Chem., 2009, 7, 4037 NH2

O

O O

OH

HO

NH

O

OH

N H

O

HN O OH

N

NH2 HOOC

OH

O

H N

O

N H

O O

O

O

O

H N

NH2

HN

N

H N O

O

NH

O

O NH2

738 Homophymine D1 Type: Cyclic lipodepsipeptides. C75H132N16O23 Amorph. solid, [α]D = +1.9° (c = 0.65, MeOH). Source: Lithistid sponge Homophymia sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 10.6 nmol/L; MCF7, IC50 = 3.5 nmol/L; resistant MCF7, IC50 = 3.5 nmol/L; HCT116, IC50 = 1.8 nmol/L; HCT15, IC50 = 11.4 nmol/L; HT29, IC50 = 32.2 nmol/L; OVCAR-8, IC50 = 1.6 nmol/L; SK-OV-3, IC50 = 1.4 nmol/L; PC3, IC50 = 1.4 nmol/L; Vero, IC50 = 1.8 nmol/L; normal MRC-5, IC50 = 10.5 nmol/L; HL60, IC50 = 13.1 nmol/L; resistant HL60, IC50 = 21.9 nmol/L, antiproliferative; K562, IC50 = 12.9 nmol/L; MiaPaCa, IC50 = 17.6 nmol/L; SF268, IC50 = 7.9 nmol/L; A549, IC50 = 5.0 nmol/L; MDA231, IC50 = 11.1 nmol/L; MDA435, IC50 = 23.4 nmol/L; HepG2, IC50 = 80.4 nmol/L; EPC, IC50 = 7.7 nmol/L). Ref: A. Zampella, et al, Org. Biomol. Chem., 2009, 7, 4037

1.15 Cyclic Lipodepsipeptides

NH2

O

O O

OH

H 2N

NH

O

OH

O

O

O

O

H N

HOOC

OH

NH2

HN

O N

NH2

O

N H

O

HN O

OH

O

H N

N H

309

NH

N

H N O

O

O

O NH2

739 Homophymine E Type: Cyclic lipodepsipeptides. C76H133N15O24 Amorph. solid, [α]D = +5.5° (c = 0.43, MeOH). Source: Lithistid sponge Homophymia sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 6.0 nmol/L; MCF7, IC50 = 14.2 nmol/L; resistant MCF7, IC50 = 15.6 nmol/L; HCT116, IC50 = 5.5 nmol/L; HCT15, IC50 = 27.2 nmol/L; HT29, IC50 = 35.1 nmol/L; OVCAR-8, IC50 = 4.6 nmol/L; SK-OV-3, IC50 = 4.2 nmol/L; PC3, IC50 = 3.9 nmol/L; Vero, IC50 = 7.0 nmol/L; normal MRC-5, IC50 = 9.5 nmol/L; HL60, IC50 = 23.3 nmol/L, antiproliferative; resistant HL60, IC50 = 21.4 nmol/L; K562, IC50 = 22.2 nmol/L; MiaPaCa, IC50 = 18.1 nmol/L; SF268, IC50 = 8.1 nmol/L; A549, IC50 = 9.6 nmol/L; MDA231, IC50 = 13.3 nmol/L; MDA435, IC50 = 38.3 nmol/L; HepG2, IC50 = 60.5 nmol/L; EPC, IC50 = 9.5 nmol/L). Ref: A. Zampella, et al, Org. Biomol. Chem., 2009, 7, 4037 NH2

O

O O

OH

HO

NH

O

OH

N H

O

HN O OH

N

NH2 HOOC

OH

O

H N

O

N H

O O

O

O

O

H N

NH2

HN

N

H N O

O

NH

O

O NH2

310

1 Peptides

740 Homophymine E1 Type: Cyclic lipodepsipeptides. C76H134N16O23 Amorph. solid, [α]D = +3.2° (c = 0.62, MeOH). Source: Lithistid sponge Homophymia sp. (New Caledonia). Pharm: Cytotoxic (KB, IC50 = 12.5 nmol/L; MCF7, IC50 = 3.9 nmol/L; resistant MCF7, IC50 = 7.1 nmol/L; HCT116, IC50 = 2.3 nmol/L; HCT15, IC50 = 10.1 nmol/L; HT29, IC50 = 31.8 nmol/L; OVCAR-8, IC50 = 4.0 nmol/L; SK-OV-3, IC50 = 2.7 nmol/L; PC3, IC50 = 3.5 nmol/L; Vero, IC50 = 4.4 nmol/L; normal MRC-5, IC50 = 12.3 nmol/L; HL60, IC50 = 20.5 nmol/L, antiproliferative; resistant HL60, IC50 = 23.2 nmol/L; K562, IC50 = 17.8 nmol/L; MiaPaCa, IC50 = 10.6 nmol/L; SF268, IC50 = 10.1 nmol/L; A549, IC50 = 11.4 nmol/L; MDA231, IC50 = 20.0 nmol/L; MDA435, IC50 = 37.0 nmol/L; HepG2, IC50 = 62.8 nmol/L; EPC, IC50 = 29.0 nmol/L). Ref: A. Zampella, et al, Org. Biomol. Chem., 2009, 7, 4037 NH2

O H 2N

O

OH

NH

O

OH

N H

H N O

HN O OH

N

NH2 HOOC

OH

O

O

N H

O O

O

O

O

H N

NH2

HN

N

H N O

O

NH

O

O NH2

741 Kahalalide F Type: Cyclic lipodepsipeptides. C75H124N14O16 White powder, [α]D = −8° (c = 4.32, MeOH). Source: Sacoglossan Elysia rufescens (Hawaii) which feeds on green alga Bryopsis sp. Pharm: Anti-AIDS (in vitro against AIDS OI Pathogens); anti-HIV-2 (mink lung cells HIV-2, 0.5 μg/mL); immunosuppressive (mixed lymphocyte reaction (MLR) assay, IC50 = 3 μg/mL, lymphocyte viability (LCV), IC50 = 23 μg/mL); antituberculosis (Mycobacterium tuberculosis H37Rv, 12.5 μg/mL, InRt = 67%); cytotoxic (A549, IC50 = 2.5 μg/mL, HT29, IC50 = 0.25 μg/mL, CV-1, IC50 = 0.25 μg/mL, LoVo, IC50 < 1.0 μg/mL, P388, IC50 = 10 μg/mL, KB, IC50 > 10 μg/mL); antineoplastic (Phase II clin. trial, 2004); antiviral (mink lung cell HSV-2, 0.5 μg/mL, 95% reduction); antifungal (50 μg/6 mm disk: Aspergillus oryzae, IZD = 19 mm; Penicillium notatum, IZD = 26 mm; Trichophyton mentagrophytes, IZD = 34 mm; Saccharomyces cerevisiae, inactive; Candida albicans, IZD = 16 mm). Ref: M. T. Hamann, et al, JACS, 1993, 115, 5825│M. T. Hamann, et al, JOC, 1996, 61, 6594│G. Goetz, et al,

1.15 Cyclic Lipodepsipeptides

311

Tetrahedron, 1999, 55, 7739│A. E. -S. Khalid, et al, Tetrahedron, 2000, 56, 949│ A. López-Macià, et al, JACS, 2001, 123, 11398 NH2 O

HN H

H

HN

O

O O

N H

NH

O

O O

H

O

N O

NH

H H N

O

O Ph

NH

N H

O

HN

O

OH

N H

O

HN

O

N H

742 Kahalalide R Type: Cyclic lipodepsipeptides. C77H126N14O17 Amorph. solid, [α]D25 = −18° (c = 0.35, MeOH). Source: Sacoglossan Elysia grandifolia. Pharm: Cytotoxic (MCF7, higher activity than Kahalalide F). Ref: M. Ashour, et al, JNP, 2006, 69, 1547│S. Tilvi, et al, J. Mass Spectrom., 2007, 42, 70

O

H 2N

O N H

O

H

5

N H

H

O

N HN O

NH

O

O

HN

O

O

NH O N H

NH H N

O

O

NH

H N

O

O NH HOOC

O

5'

312

1 Peptides

743 Kailuin A Type: Cyclic lipodepsipeptides. C35H63N5O9 Clear oil liquid, [α]D = +8.6° (c = 1.0, MeOH). Source: An unidentified marine-derived bacterium BH-107 from driftwood (Kailua beach, Oahu). Pharm: Cytotoxic (A549, GI50 = 3 μg/mL, MCF7, GI50 = 3 μg/mL, HT29, GI50 = 3 μg/mL). Ref: G. G. Harrigan, et al, Tetrahedron, 1997, 53, 1577

H N

OH

HN O O

O

O

H N

HN

H N

OH O

O O

744 Kailuin B Type: Cyclic lipodepsipeptides. C37H67N5O9 Oil, [α]D = +9.3° (c = 1 MeOH). Source: Marine-derived bacterium Vibrio sp. (Okinawa), an unidentified marine-derived bacterium BH-107 (from driftwood, Kailua beach, Oahu). Pharm: Algicide (dinofiagellate Prorocentrum micans, strong); cytotoxic (A549, GI50 = 2 μg/mL, MCF7, GI50 = 2 μg/mL, HT29, GI50 = 3 μg/mL). Ref: G. G. Harrigan, et al, Tetrahedron, 1997, 53, 1577│R. Raju, et al, Tet. Lett., 2012, 53, 6905

H N

HN O O

O

O

OH H N OH

HN

H N

O

O O

745 Kailuin C Type: Cyclic lipodepsipeptides. C37H67N5O9 Clear oil liquid, [α]D = +10.0° (c = 1.0, MeOH). Source: An unidentified marine-derived bacterium BH-107 from driftwood (Kailua beach, Oahu). Pharm: Cytotoxic (A549, GI50 = 3 μg/mL, MCF7, GI50 = 4 μg/mL, HT29, GI50 = 3 μg/mL). Ref: G. G. Harrigan, et al, Tetrahedron, 1997, 53, 1577

1.15 Cyclic Lipodepsipeptides

H N

HN O

O O

OH H N

O HN

H N

313

OH O

O O

746 Kailuin D Type: Cyclic lipodepsipeptides. C39H69N5O9 Clear oil liquid, [α]D = +9.5° (c = 1.0, MeOH). Source: An unidentified marine-derived bacterium BH-107 from driftwood (Kailua beach, Oahu). Pharm: Cytotoxic (A549, GI50 = 2 μg/mL, MCF7, GI50 = 3 μg/mL, HT29, GI50 = 2 μg/mL). Ref: G. G. Harrigan, et al, Tetrahedron, 1997, 53, 1577

H N

OH

HN O

O O

O

H N

HN

H N

OH O

O O

747 Kailuin E Type: Cyclic lipodepsipeptides. C39H71N5O9 Source: Marine-derived bacteria Vibrio sp. (Okinawa) and Vibrio sp. G1363. Pharm: Algicide; surfactant. Ref: Y. Kawabata, et al, Japan. Pat., 2000, 245497; CA, 133, 221694w

O H N

HN O

O

NH

HO

O O

HN H N

H

O

H O

OH

314

1 Peptides

748 Malevamide E Type: Cyclic lipodepsipeptides. C60H94N8O11 Amorph. solid, [α]D25 = −100° (c = 0.057, CH2Cl2). Source: Cyanobacterium Symploca laeteviridis Pharm: Anticancer-Cell-Effect (model: HEK, mechanism: Calcium influx inhibition, IC50 (estimated) = 9 μmol/L). Ref: B. Adams, et al, JNP, 2008, 71, 750 O N

N O O

O N

O

O

H N

N

O

N O

O N

O

N H

O

749 Massetolide A Type: Cyclic lipodepsipeptides. C55H97N9O16 Solid, mp 237–238 °C (dec), [α]D = +45.9° (EtOH). Source: Marine-derived bacterium Pseudomonas sp. various marine and terrestrial bacterium Pseudomonas fluorescens. Pharm: Antituberculosis (Mycobacterium tuberculosis, MIC = 5–10 μg/mL); antimycobacterial (Mycobacterium avium-intracellulare, MIC = 2.5–5 μg/mL). Ref: J. Gerard, et al, JNP, 1997, 60, 223│A. E. -S. Khalid, et al, Tetrahedron, 2000, 56, 949 O HN HN

O

O O

NH

NH O

OH

OH O

NH O

HO

O

H N

O O

N H

N H

H N O

OH

O

750 Massetolide B Type: Cyclic lipodepsipeptides. C56H99N9O16 Solid. Source: Marine-derived bacterium Pseudomonas sp. MK90e85 and MK91CC8 (cultures, from unidentified red alga and marine tube worm, British Columbia). Pharm: Antimicrobial. Ref: J. Gerard, et al, JNP, 1997, 60, 223

1.15 Cyclic Lipodepsipeptides

315

O HN HN

O

O

O

OH

NH OH NH NH

O HO

O O O

N H

O

H N

H N

N H

O

O

OH

O

751 Massetolide C Type: Cyclic lipodepsipeptides. C57H101N9O16 Solid. Source: Marine-derived bacterium Pseudomonas sp. MK90e85 and MK91CC8 (cultures, from unidentified red alga and marine tube worm, British Columbia). Pharm: Antimicrobial. Ref: J. Gerard, et al, JNP, 1997, 60, 223 O HN HN

O

O

O

OH

NH OH NH NH

O HO

O O O

N H

O

H N O

N H

H N O

OH

O

752 Massetolide D Type: Cyclic lipodepsipeptides. C55H97N9O16 Solid. Source: Marine-derived bacterium Pseudomonas sp. MK90e85 and MK91CC8 (cultures, from unidentified red alga and marine tube worm, British Columbia). Pharm: Antimicrobial. Ref: J. Gerard, et al, JNP, 1997, 60, 223 O HN HN

O

O

O

OH

NH OH NH O

NH

O O O

HO N H

O

H N O

O

N H

H N O

OH

316

1 Peptides

753 Massetolide E Type: Cyclic lipodepsipeptides. C53H93N9O16 Solid. Source: Marine-derived bacterium Pseudomonas sp. MK90e85 and MK91CC8 (cultures, from unidentified red alga and marine tube worm, British Columbia). Pharm: Antimicrobial. Ref: J. Gerard, et al, JNP, 1997, 60, 223 O HN HN

O

O O

NH

NH O

NH

O

OH

OH

O

HO

O

H N

N H

O O

N H

H N O

OH

O

754 Massetolide F Type: Cyclic lipodepsipeptides. C54H95N9O16 Solid. Source: Marine-derived bacterium Pseudomonas sp. MK90e85 and MK91CC8 (cultures, from unidentified red alga and marine tube worm, British Columbia). Pharm: Antimicrobial. Ref: J. Gerard, et al, JNP, 1997, 60, 223 O HN HN

O

O O

NH

NH O

OH

OH O

NH O

HO N H

O

O

H N O

N H

H N O

OH

O

755 Massetolide G Type: Cyclic lipodepsipeptides. C55H97N9O16 Solid. Source: Marine-derived bacterium Pseudomonas sp. MK90e85 and MK91CC8 (cultures, from unidentified red alga and marine tube worm, British Columbia). Pharm: Antimicrobial. Ref: J. Gerard, et al, JNP, 1997, 60, 223

1.15 Cyclic Lipodepsipeptides

317

O HN HN

O

O O

NH

NH O

NH

O

OH

OH

O

HO

O

H N

O O

N H

H N

N H

O

OH

O

756 Massetolide H Type: Cyclic lipodepsipeptides. C56H99N9O16 Solid. Source: Marine-derived bacterium Pseudomonas sp. MK90e85 and MK91CC8 (cultures, from unidentified red alga and marine tube worm, British Columbia). Pharm: Antimicrobial. Ref: J. Gerard, et al, JNP, 1997, 60, 223 O HN HN

O NH

O

NH O

NH

O O O

HO N H

O

OH

OH O

H N O

N H

H N O

OH

O

757 Mirabamide B Type: Cyclic lipodepsipeptides. C72H111ClN12O25 Amorph. powder, [α]D20 = −2° (c = 0.1, MeOH). Source: Lithistid sponge Siliquariaspongia mirabilis (Nama I., southeast of Chuuk Lagoon, Federated States of Micronesia). Pharm: Cytotoxic (HCT116, IC50 = 2.22 μmol/L). Ref: A. Plaza, et al, JNP, 2007, 70, 1753│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev)

318

1 Peptides

HO NH2 Cl

O

H O

HN

4''

O O HO

O

HO

O

O

O

HN

OH

O O

O

OH OH

NH

O

N H

NH

H

N

H

HN

O O

4'''

O

N

OH

H

NH HN

H N O

O

O

758 Mirabamide C Type: Cyclic lipodepsipeptides. C66H104ClN13O21 Amorph. powder, [α]D20 = −1.5° (c = 0.06, MeOH). Source: Lithistid sponge Siliquariaspongia mirabilis (Nama I., southeast of Chuuk Lagoon, Federated States of Micronesia), sponge Stelletta calvosa (Torres Strait, Queensland, Australia). Pharm: Anti-HIV (HIV-1 neutralization assay, host cell TZM-bl cell line, HXB2 (T-cell tropic) viral strain, IC50 = 140 nmol/L; SF162 (macrophage-tropic) viral strain, IC50 = 1.01 μmol/L); anti-HIV (HIV-1 fusion assay, LAV (T-cell tropic) viral strain, IC50 = 1.3 μmol/L); anti-HIV (HIV-1 neutralization assay, host cell TZM-bl cell line, IC50 = 2.2 μmol/L); anti-HIV (HIV-1 neutralization assay, YU2-V3 viral strain, IC50 = 123 nmol/L). Ref: A. Plaza, et al, JNP, 2007, 70, 1753│Z. Lu, et al, JNP, 2011, 74, 185│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev) HO H N

H O

O

O HO

N H

O HN

NH2 Cl

O H

OH H NH2

4''

N H

O 4'''

H

N

O

OH

O

HN

NH

O O O

O O

NH H N

O

H N

N

H

OH

O O

759 Mirabamide D Papuamide A 4′′′-O-α-L-rhamnopyranoside Type: Cyclic lipodepsipeptides. C72H115N13O25 Amorph. powder, [α]D20 = −1.5° (c = 0.06, MeOH). Source: Lithistid

1.15 Cyclic Lipodepsipeptides

319

sponge Siliquariaspongia mirabilis (Nama I., southeast of Chuuk Lagoon, Federated States of Micronesia). Pharm: Anti-HIV (HIV-1 neutralization assay, host cell TZM-bl cell line, HXB2 (T-cell tropic) viral strain, IC50 = 189 nmol/L; SF162 (macrophagetropic) viral strain, IC50 = 1.31 μmol/L); anti-HIV (HIV-1 fusion assay, LAV (T-cell tropic) viral strain, IC50 = 3.9 μmol/L); anti-HIV (HIV-1 neutralization assay, host cell TZM-bl cell line, IC50 = 3.9 μmol/L). Ref: A. Plaza, et al, JNP, 2007, 70, 1753│P. L. Winder, et al, Mar. Drugs, 2011, 9, 2643 (rev) HO H H N O HO

NH2

O

O HN

N H

O

O

N H

OH

O

4''

H

N H

O

H NH2

O

HN

O O

NH

OH OH

O OH N H

H N

H N

O

O O

HO NH

O

O

4'''

O

O

760 Stellatolide A Type: Cyclic lipodepsipeptides. C66H107N15O22 Source: Sponge Ecionemia acervus (Madagascar). Pharm: Cytotoxic (A549, natural, GI50 = 0.08 μmol/L, synthetic, GI50 = 0.08 μmol/L; HT29, natural, GI50 = 0.43 μmol/L, synthetic, GI50 = 0.38 μmol/L; MDA-MB-231, natural, GI50 = 0.21 μmol/L, synthetic, GI50 = 0.26 μmol/L). Ref: M. J. Martíın, et al, JACS, 2014, 136, 6754 NH2

O

OH H 2N O

HN

OH

O N H O

H N O OH

O N H NH2

O

O

O

H N

O

N H

HN

O

O

O N O

O N H

O

NH

O N O NH2

OH

320

1 Peptides

761 Stellatolide B Type: Cyclic lipodepsipeptides. C65H105N15O22 Source: Sponge Ecionemia acervus (Madagascar). Pharm: Cytotoxic (A549, GI50 = 0.64 μmol/L; HT29, GI50 = 1.15 μmol/L; MDA-MB-231, GI50 = 070 μmol/L). Ref: M. J. Martíın, et al, JACS, 2014, 136, 6754 NH2

O

OH H 2N O

OH

O

H N

N H O

HN

O

O N H NH2

OH

O

O

O

H N

O

N H

HN

O

O

O N

O

O

O

NH

O N

N H

O NH2

OH

762 Stellatolide C Type: Cyclic lipodepsipeptides. C66H109N15O23 Source: Sponge Ecionemia acervus (Madagascar). Pharm: Cytotoxic (A549, GI50 = 4.73 μmol/L; HT29, GI50 > 6.75 μmol/L; MDA-MB-231, GI50 > 6.75 μmol/L). Ref: M. J. Martíın, et al, JACS, 2014, 136, 6754 O

OH H 2N O

HN

OH

O N H O

H N O

O N H NH2

NH2 O

O

H N

O

N H

O HO

HN

O

OH N O

OH

O

O

O

N H

O

NH

N O NH2

OH

763 Stellatolide D Type: Cyclic lipodepsipeptides. C66H107N15O21 Source: Sponge Ecionemia acervus (Madagascar). Pharm: Cytotoxic (A549, GI50 = 0.21 μmol/L; HT29, GI50 = 0.71 μmol/L; MDA-MB-231, GI50 = 0.31 μmol/L). Ref: M. J. Martíın, et al, JACS, 2014, 136, 6754

1.15 Cyclic Lipodepsipeptides

O OH

O H 2N O

N H O

HN

H N O

NH2

O

O

NH2

OH

O

O

H N

N H

321

N H

O

O HN

O

O N

O

O

O

NH

O N

N H

O NH2

OH

764 Stellatolide E Type: Cyclic lipodepsipeptides. C65H105N15O22 Source: Sponge Ecionemia acervus (Madagascar). Pharm: Cytotoxic (A549, GI50 = 0.90 μmol/L; HT29, GI50 = 2.69 μmol/L; MDA-MB-231, GI50 = 1.60 μmol/L). Ref: M. J. Martíın, et al, JACS, 2014, 136, 6754 O

OH H 2N O

HN

OH

O N H O

H N O OH

NH2

O N H NH2

O

O

O

H N

O

N H

HN

O

O

O N O

O N H

O

NH

O N O NH2

OH

765 Stellatolide F Type: Cyclic lipodepsipeptides. C66H104N14O21 Source: Sponge Ecionemia acervus (Madagascar). Pharm: Cytotoxic (A549, GI50 = 1.23 μmol/L; HT29, GI50 > 6.48 μmol/L; MDA-MB-231, GI50 = 2.14 μmol/L). Ref: M. J. Martíın, et al, JACS, 2014, 136, 6754

322

1 Peptides

O OH

O H 2N O

N H O

HN

NH2

O

H N

N H

O

O

OH

O

O

H N

N H

O

O HN

O

O N

O

O

O

NH

O N

N H

O NH2

OH

766 Stellatolide G Type: Cyclic lipodepsipeptides. C66H104N14O22 Source: Sponge Ecionemia acervus (Madagascar). Pharm: Cytotoxic (A549, HT29 and MDA-MB-231, all GI50 > 6.41 μmol/ L). Ref: M. J. Martíın, et al, JACS, 2014, 136, 6754 NH2

O

OH H 2N O

HN

OH

O N H O

H N O OH

O N H

O

O

O

H N

O

N H

HN

O

O

O N O

O N H

O

NH

O N O NH2

OH

767 Thalassospiramide A Type: Cyclic lipodepsipeptides. C48H75N7O13 Oil, [α]D = −29° (c = 0.07, MeCN). Source: Marine bacterium Thalassospira sp. CNJ-328. Pharm: Immunosuppressant. Ref: D. -C. Oh, et al, Org. Lett., 2007, 9, 1525

1.15 Cyclic Lipodepsipeptides

OH

O

OH

7

N H HO

O

H N

N H

NH O

O

NH

O

O

H N

323

O N

O O

OH

768 Viscosin Type: Cyclic lipodepsipeptides. C54H95N9O16 Needles or powder, mp 270–273 °C, [α]D29 = −168.3° (c = 1, EtOH). Source: Marine-derived bacterium Pseudomonas sp. from an unidentified marine tube worm. Pharm: Antituberculosis (Mycobacterium tuberculosis, MIC = 10–20 μg/mL); antimycobacterial (Mycobacterium aviumintracellulare, MIC = 5–10 μg/mL). Ref: J. Gerard, et al, JNP, 1997, 60, 223│ A. E. -S. Khalid, et al, Tetrahedron, 2000, 56, 949 O HN O

HN NH

O

O

OH NH

NH O O O OH HN

OH

O

O

H N O

O

N H

H N O

OH

769 Sungsanpin Type: Cyclic lipodepsipeptides. C77H109N17O20 Source: Marine-derived streptomycete Streptomyces sp. (deep sea sediment, Jeju I., R. O. Korea). Pharm: Cytotoxic (cell invasion assay, inhibits A549). Ref: S. Um, et al, JNP, 2013, 76, 873

O OH O

O O

NH O N H

N H

H N O OH

O

O N H

N H

O

N H HO

N H

NH

H N

O O

N H

O O

N H

OH

HN HN O O N H

N

O NH2

324

1 Peptides

1.16 Cyclic Depsipeptides with Thiazole 770 Apratoxin A Type: Cyclic depsipeptides with thiazole. C45H69N5O8S Amorph. solid, [α]D25 = −161° (c = 1.3, MeOH). Source: Cyanobacterium Lyngbya majuscula (Guam). Pharm: Anticancer-Cell-Effect (model: HeLa, mechanism: cell cycle inhibition) (Ma, 2006); Anticancer-Cell-Effect (model: U2OS, mechanism: reversibly inhibits secretory pathway by preventing cotranslational translocation) (Liu, 2009); cytotoxic (hmn tumor cell lines, IC50 = 0.36–0.52 nmol/L) (Luesch, 2001); antineoplastic (in vivo, a colon tumor, marginally active; a mammary tumor, ineffective) (Luesch, 2001); cytotoxic (KB, IC50 = 0.52 nmol/L; LoVo, IC50 = 0.36 nmol/L) (Luesch, 2002); cytotoxic (MTT assay, U2OS, IC50 = 10 nmol/L; HT29, IC50 = 1.4 nmol/L; HeLa, IC50 = 10 nmol/L) (Matthew, 2008); cytotoxic (HCT116, IC50 = 1 ng/mL (1.21 nmol/L)) (Tidgewell, 2010); G1 cell cycle arrest and induction of apoptosis. Ref: H. Luesch, et al, JACS, 2001, 123, 5418│H. Luesch, et al, Bioorg. Med. Chem. 2002, 10, 1973│D. Ma, et al, Chemistry, 2006, 12, 7615│S. Matthew, et al, JNP, 2008, 71, 1113│Y. Liu, et al, Apratoxin a. Mol. Pharmacol. 2009, 76, 91│K. Tidgewell, et al, Chem Bio Chem, 2010, 11, 1458│H. Choi, et al, JNP, 2010, 73, 1411 S

H N N O

N

O O N

OH

O O

O

12

H

O

N

771 Apratoxin A sulfoxide Type: Cyclic depsipeptides with thiazole. C45H69N5O9S Source: Cyanobacterium Moorea producens (Nabq Mangroves, Gulf of Aqaba, Red Sea). Pharm: Cytotoxic (NCI-H460). Ref: C. C. Thornburg, et al, JNP, 2013, 76, 1781 O S H N

O

O

N

O N

N O O

O N

O

OH

1.16 Cyclic Depsipeptides with Thiazole

325

772 Apratoxin B Type: Cyclic depsipeptides with thiazole. C44H67N5O8S Amorph. solid, [α]D25 = −73° (c = 0.2, MeOH). Source: Cyanobacterium Lyngbya sp. (Guam and Palau). Pharm: Cytotoxic (KB, IC50 = 21.3 nmol/L; LoVo, IC50 = 10.8 nmol/L). Ref: H. Luesch, et al, Bioorg. Med. Chem. 2002, 10, 1973 O

S

H N N N

O O HN

O

OH O

O

12

H

O

N

773 Apratoxin C Type: Cyclic depsipeptides with thiazole. C44H67N5O8S Amorph. solid, [α]D25 = −171° (c = 0.22, MeOH). Source: Cyanobacterium Lyngbya sp. (Guam and Palau). Pharm: Cytotoxic (KB, IC50 = 1.0 nmol/L; LoVo, IC50 = 0.73 nmol/L). Ref: H. Luesch, et al, Bioorg. Med. Chem. 2002, 10, 1973 O

S

H N N N

O O N

O

OH O

O

12

H

N

O

774 Apratoxin D Type: Cyclic depsipeptides with thiazole. C48H75N5O8S Pale yellow powder, [α]D25 = −95.1° (c = 0.13, MeOH). Source: Cyanobacteria Lyngbya majuscula and Lyngbya sordida Pharm: Cytotoxic (MTT assay, H460, IC50 = 2.6 nmol/L). Ref: M. Gutierrez, et al, JNP, 2008, 71, 1099

326

1 Peptides

O

S

H N N

O O N

N O

OH

O

O

H

12

H

N

O

S

775 Apratoxin E Type: Cyclic depsipeptides with thiazole. C43H65N5O7S Amorph. solid, [α]D20 = −69° (c = 0.12, MeOH). Source: Cyanobacterium Lyngbya bouillonii (Palmyra, Guam). Pharm: Cytotoxic (MTT assay, U2OS, IC50 = 59 nmol/L; HT29, IC50 = 21 nmol/L; HeLa, IC50 = 72 nmol/L). Ref: S. Matthew, et al, JNP, 2008, 71, 1113 O

S

H N N N

O O N

O O

O

12

H

N

O

776 Apratoxin F Type: Cyclic depsipeptides with thiazole. C44H69N5O8S [α] = −249°. Source: Cyanobacterium Lyngbya bouillonii (Palmyra Atoll, Central Pacific Ocean). Pharm: Cytotoxic (hemocytometer counting assay, HCT116, IC50 = 31 ng/mL (36.7 nmol/L)); cytotoxic (H460, IC50 = 2 nmol/L). Ref: K. Tidgewell, et al, Chem Bio Chem, 2010, 11, 1458

1.16 Cyclic Depsipeptides with Thiazole

327

O

S

H N N N

O O N

O

OH

O

O

12

H

N

O

777 Apratoxin G Type: Cyclic depsipeptides with thiazole. C43H67N5O8S [α] = −206°. Source: Cyanobacterium Lyngbya bouillonii (Palmyra Atoll, Central Pacific Ocean). Pharm: Cytotoxic (hemocytometer counting assay, HCT116, IC50 = 31 ng/mL (mixture of apratoxins F and G)); cytotoxic (H460, IC50 = 14 nmol/L). Ref: K. Tidgewell, et al, Chem Bio Chem, 2010, 11, 1458 O

S

H N N N

O O N

O

OH

O

O

12

N

O

778 Apratoxin H Type: Cyclic depsipeptides with thiazole. C46H71N5O8S Source: Cyanobacterium Moorea producens (Nabq Mangroves, Gulf of Aqaba, Red Sea). Pharm: Cytotoxic (NCI-H460, much more potent than apratoxin A sulfoxide). Ref: C. C. Thornburg, et al, JNP, 2013, 76, 1781

328

1 Peptides

S H N

O

N

O

N

OH

O

O

O

O

N

O

N

779 Deacetylhectochlorin Type: Cyclic depsipeptides with thiazole. C25H32Cl2N2O8S2 Amorph. solid, [α]D20 = −26° (c = 0.1, MeOH). Source: Sea hare Bursatella leachii. Pharm: Stimulator of actin assembly (potent); cytotoxic (KB, ED50 = 0.31 μmol/L; NCI-H187, ED50 = 0.32 μmol/L; BC, ED50 = 1.03 μmol/L). Ref: S. Suntornchashwej, et al, JNP, 2005, 68, 951 OH

S

O N O

O O

HO

Cl

Cl

N O

S

780 (E)-Dehydroapratoxin A Type: Cyclic depsipeptides with thiazole. C45H67N5O7S Semisynthetic compound, colorless amorphous solid, [α]D25 = −133° (c = 0.30, MeOH). Source: Cyanobacterium Lyngbya sp. Pharm: Cytotoxic (KB, IC50 = 37.6 nmol/L; LoVo, IC50 = 85.1 nmol/L). Ref: H. Luesch, et al, Bioorg. Med. Chem., 2002, 10, 1973 S

H N

O

N

O O N

N O

O

O N

O

1.16 Cyclic Depsipeptides with Thiazole

329

781 Grassypeptolide A Type: Cyclic depsipeptides with thiazole. C56H79N9O10S2 Amorph. solid, [α]D20 = +76° (c = 0.1, CH2Cl2). Source: Cyanobacterium Lyngbya confervoides (Florida Keys). Pharm: Cytotoxic (HT29, IC50 = 1.22 μmol/L, control Taxol, IC50 = 0.0022 μmol/L, HeLa, IC50 = 1.01 μmol/L, Taxol, IC50 = 0.0017 μmol/L). Ref: J. C. Kwan, et al, JOC, 2010, 75, 8012

N N O O

O

N

O O HN O

H SO

O O N H

HO

N

28

N

S

NH

N

782 Grassypeptolide B Type: Cyclic depsipeptides with thiazole. C55H77N9O10S2 Colorless amorphous solid, [α]D20 = +109°. Source: Cyanobacterium Lyngbya confervoides. (Florida Keys). Pharm: Cytotoxic (HT29, IC50 = 4.97 μmol/L, control Taxol, IC50 = 0.0022 μmol/L, HeLa, IC50 = 2.93 μmol/L, Taxol, IC50 = 0.0017 μmol/L). Ref: J. C. Kwan, et al, JOC, 2010, 75, 8012

N N O O

O

N

O O HN

N

O O O HO

N H

28

N

H S

SO N

NH

783 Grassypeptolide C Type: Cyclic depsipeptides with thiazole. C56H79N9O10S2 Colorless amorphous solid, [α]D20 = +18°. Source: Cyanobacterium Lyngbya confervoides. (Florida Keys). Pharm: Cytotoxic (HT29, IC50 = 0.0767 μmol/L, control Taxol, IC50 = 0.0022 μmol/L, HeLa,

330

1 Peptides

IC50 = 0.0446 μmol/L, Taxol, IC50 = 0.0017 μmol/L). Ref: J. C. Kwan, et al, JOC, 2010, 75, 8012

N N O

O

O N

O O HN

N

O O O HO

N H

28

S

SO NH

N

N

784 Grassypeptolide D Type: Cyclic depsipeptides with thiazole. C57H81N9O10S2 Colorless amorphous solid, [α]D21 = +25.9° (c = 0.15, CH2Cl2). Source: Cyanobacterium Leptolyngbya sp. (SS Thistlegorm shipwreck, Red Sea). Pharm: Cytotoxic (HeLa, IC50 = 335 nmol/L; neuro-2a, IC50 = 599 nmol/L). Ref: C. C. Thornburg, et al, JNP, 2011, 74, 1677

N N O O

O O

N

O

HN O 7R

HO

N H

N O O

S

11R

N

N

S

O NH

785 Grassypeptolide E Type: Cyclic depsipeptides with thiazole. C57H81N9O10S2 Colorless amorphous solid, [α]D21 = +13.2° (c = 0.15, CH2Cl2). Source: Cyanobacterium Leptolyngbya sp. (SS Thistlegorm shipwreck, Red Sea). Pharm: Cytotoxic (HeLa, IC50 = 192 nmol/L; neuro-2a, IC50 = 407 nmol/L). Ref: C. C. Thornburg, et al, JNP, 2011, 74, 1677

1.16 Cyclic Depsipeptides with Thiazole

331

N N O O

O O

N

O

HN O 7S

HO

N H

N O O

S

O

11S

NH

N

N

S

786 Grassypeptolide F Type: Cyclic depsipeptides with thiazole. C60H79N9O9S2 Source: Cyanobacterium Lyngbya majuscula (Ngerderrak Reef, Palau). Pharm: Transcription factor AP-1 inhibitor. Ref: W. L. Popplewell, et al, JNP, 2011, 74, 1686

N N O

O

O

O

N

O

HN N

O O O N H

N

S N

S

O NH

787 Grassypeptolide G Type: Cyclic depsipeptides with thiazole. C59H77N9O9S2 Source: Cyanobacterium Lyngbya majuscula (Ngerderrak Reef, Palau). Pharm: Transcription factor AP-1 inhibitor. Ref: W. L. Popplewell, et al, JNP, 2011, 74, 1686

332

1 Peptides

N N O

O

O

O

N

O

HN N

O O O N H

S

NH

N

N

S

O

788 Halipeptin A Type: Cyclic depsipeptides with thiazole. C31H54N4O7S Amorph. solid, [α]D = −16.6° (c = 0.03, CHCl3). Source: Sponge Haliclona sp. Pharm: Anti-inflammatory (potent). Ref: A. Randazzo, et al, JACS, 2001, 123, 10870│C. D. Monica, et al, Tet. Lett., 2002, 43, 5707

S O

HN N O

O

N

OH H 5'

H O

H N O

O

789 Hectochlorin Type: Cyclic depsipeptides with thiazole. C27H34Cl2N2O9S2 Pale yellow solid [α]D25 = −8.7° (c = 1.04, MeOH). Source: Cyanobacterium Lyngbya majuscula, sea hare Bursatella leachii. Pharm: Anticancer-Cell-Effect (model: CA46, IC50 = 0.02 μmol/L, normal PtK2, IC50 = 0.3 μmol/L, mechanism: cell cycle inhibition) (Marquez, 2002); antifungal; cytotoxic (CA46, induces arrest in G2/M phase); actin polymerisation promoter (EC50 = (20 ± 0.6)μmol/L) (Marquez, 2002); stimulator of actin assembly (potent); cytotoxic (KB, ED50 = 0.86 μmol/L; NCI-H187, ED50 = 1.20 μmol/L). Ref: B. L. Marquez, et al, JNP, 2002, 65, 866│S. Suntornchashwej, et al, JNP, 2005, 68, 951│M. Costa, et al, Mar. Drugs, 2012, 10, 2181 (rev)

1.16 Cyclic Depsipeptides with Thiazole

OH

S

O

333

N O

O

O O

O

Cl

Cl

N O

S O

790 Hoiamide A Type: Cyclic depsipeptides with thiazole. C44H71N5O10S3 Source: Cyanobacteria Lyngbya majuscula and Phormidium gracile (assemblage, Papua New Guinea). Pharm: Anticancer-Cell-Effect (model: primary cultures of neocortical neurons from embryonic mice, mechanism: Sodium channel VGSC activator); Sodium channel VGSC activator (activation of mouse neuroblastoma cells, EC50 = 1.7 μmol/L); Ca2+ oscillation inhibitor (EC50 = 45.6 nmol/L); cytotoxic (H460, IC50 = 11.2 μmol/L; neuro-2a, IC50 = 2.1 μmol/L). Ref: H. Choi, et al, JNP, 2010, 73, 1411 S S

O

N

N

NH N

S

HO O O

O

H N O

O

H

OH O

OH

791 Hoiamide B Type: Cyclic depsipeptides with thiazole. C45H73N5O10S3 Source: An unidentified cyanobacterium PNG-4-28-06-1 (assemblage, Gallows Reef, Papua New Guinea, 2006). Pharm: Anticancer-Cell-Effect (model: primary cultures of neocortical neurons from embryonic mice, mechanism: Sodium channel VGSC activator); Sodium channel VGSC activator (activation of mouse neuroblastoma cells, EC50 = 3.9 μmol/L); Ca2+ oscillation inhibitor (EC50 = 79.8 nmol/L); cytotoxic (H460, IC50 = 8.3 μmol/L; neuro-2a, inactive). Ref: H. Choi, et al, JNP, 2010, 73, 1411

334

1 Peptides

S O

S

N

N

NH S

N HO

O O

O

O

H N

OH O

H

O

OH

792 Largazole Type: Cyclic depsipeptides with thiazole. C29H42N4O5S3 Amorph. solid, [α]D20 = +22° (c = 0.1, MeOH). Source: Cyanobacterium Symploca sp. (Florida). Pharm: Cytotoxic (MTT assay, differential growth inhibition, MDA-MB-231, GI50 = 7.7 nmol/L, NMuMG, GI50 = 122 nmol/L; U2OS, GI50 = 55 nmol/L, NIH3T3, GI50 = 480 nmol/L); cytotoxic (MTT assay, A549 and HCT116); histone deacetylase inhibitor; antiproliferative. Ref: K. Taori, et al, JACS, 2008, 130, 1806│X. Zeng, et al, Org. Lett., 2010, 12, 1368 S O

S N

N O

O

HN

NH

O O S

793 Lyngbyabellin A Type: Cyclic depsipeptides with thiazole. C29H40Cl2N4O7S2 Cryst. (CH2Cl2/ 6-methylheptane), mp 150–152 °C, [α]D27 = −74° (c = 0.5, CHCl3). Source: Cyanobacterium Lyngbya majuscula (Guam and the Dry Tortugas National Park, Florida). Pharm: Cytotoxic (KB, IC50 = 0.03 μg/mL; LoVo, IC50 = 0.50 μg/mL); antineoplastic (in vivo, toxic to mice, lethal dose = 2.4–8.0 mg/kg; at 1.2–1.5 mg/kg sublethal doses, no antitumor activity against C38 or M16); disruptor of cellular microfilament network (normal fibroblasts, 0.01–5.0 μg/mL); anticancer-Cell-Effect (model: CA46, mechanism: cell cycle inhibition) (Marquez, 2002); anticancer-CellEffect (model: rat aorta A-10 cells, mechanism: microfilament disruption) (Luesch, 2000). Ref: H. Luesch, et al, JNP, 2000, 63, 611; 1437│K. E. Milligan, et al, JNP, 2000, 63, 1440│F. Yokokawa, et al, Tet. Lett., 2001, 42, 4171│B. L. Marquez, et al, JNP, 2002, 65, 866

1.16 Cyclic Depsipeptides with Thiazole

335

O H

N H

HN

S

O

N

N

S

O

O

O Cl

HO

O

Cl

794 Lyngbyabellin B Tortugamide Type: Cyclic depsipeptides with thiazole. C28H40Cl2N4O7S2 Amorph. solid, [α]D25 = −152° (c = 0.06, CHCl3), [α]D = +33° (c = 0.2, CH2Cl2). Source: Cyanobacterium Lyngbya majuscula (Guam and the Dry Tortugas National Park, Florida). Pharm: Cytotoxic (KB, IC50 = 0.10 μg/mL, LoVo, IC50 = 0.83 μg/mL); cytotoxic (CA46, induces arrest in G2/M phase); anticancer-Cell-Effect (model: CA46, IC50 = 0.1 μmol/L, normal kindey cells of kangaroo rat Potorous tridictylis PtK2 cells, IC50 = 1.0 μmol/L, mechanism: cell cycle inhibition) (Marquez, 2002); actin polymerisation promoter (EC50 = (20 ± 0.6)μmol/L) (Marquez, 2002); antifungal (Candida albicans, LD50 = 3.0 ppm); LD50 (brine shrimp) = 3.0 μmol/L. Ref: H. Luesch, et al, JNP, 2000, 63, 611│H. Luesch, et al, JNP, 2000, 63, 1437│K. E. Milligan, et al, JNP, 2000, 63, 1440│B. L. Marquez, et al, JNP, 2002, 65, 866 O N H

HN O S HO

S N

N O O

O

O Cl Cl

795 Lyngbyabellin C Type: Cyclic depsipeptides with thiazole. C24H30Cl2N2O8S2 Amorph. solid, [α]D25 = −10° (c = 0.1, CHCl3). Source: Cyanobacterium Lyngbya sp. Pharm: Cytotoxic (KB, IC50 = 2.1 μmol/L; LoVo, IC50 = 5.3 μmol/L). Ref: H. Luesch, et al, Tetrahedron, 2002, 58, 7959

336

1 Peptides

OH O

S N

O S

N O

O

O

Cl

Cl

O HO

796 Lyngbyabellin D Type: Cyclic depsipeptides with thiazole. C38H55Cl2N3O13S2 Powder, [α]D25 = +20° (c = 0.4, CHCl3). Source: Cyanobacterium Lyngbya sp. Pharm: Cytotoxic (KB, IC50 = 0.1 μmol/L). Ref: P. G.Williams, et al, JNP, 2003, 66, 595 O

O

HO O

S O

O NH

N O

N

S

O

H

O

O

O Cl

Cl

O HO

797 Obyanamide Type: Cyclic depsipeptides with thiazole. C30H41N5O6S Powder, [α]D27 = +20° (c = 0.04, MeOH). Source: Cyanobacterium Lyngbya confervoides. Pharm: Cytotoxic (KB, IC50 = 0.58 μg/mL; LoVo). Ref: P. G. Williams, et al, JNP, 2002, 65, 29 O N

HN

NH S

O N

O

O

O

N O

1.17 Cyclic Depsipeptides with Oxazole and Thiazole 798 TP-1161 Type: Cyclic depsipeptides with oxazole and thiazole. C50H47N15O13S3 Source: Marine-derived bacterium Nocardiopsis sp. (sediment, Trondheim Fjord, Norway).

1.18 Cyclic Depsipeptides with AHP

337

Pharm: Antibacterial (a range of gram-positive bacteria including VREF, MIC = 1 μg/mL, potent); gene cluster for biosynthesis was identified, isolated and analysed. Ref: K. Engelhardt, et al, Appl. Environ. Microbiol., 2010, 76, 4969; 7093 O N H

N O

N H

O

O

N

N S

HN HO

O

H N

O

O

NH O

NH

HN O

O

N

N O

S

S NH

HN N O

1.18 Cyclic Depsipeptides with AHP 799 Bouillomide A Type: Cyclic depsipeptides with AHP. C49H68N8O12 Amorph. solid, [α]D20 = −16° (c = 0.02, MeOH). Source: Cyanobacteria Lyngbya semiplena (Tumon Bay, Guam) and Lyngbya bouillonii (Guam). Pharm: Anticancer-Cell-Effect (model: elastase and chymotrypsin, mechanism: serine proteases inhibition); serine protease selective inhibitor (elastase, IC50 = 1.9 μmol/L; chymotripsin, IC50 = 0.17 μmol/L; trypsin, 100 μmol/L inactive) (Rubio, 2010); serine protease selective inhibitor (elastase, IC50 = 0.21 μmol/L) (Kwan, 2009). Ref: J. C. Kwan, et al, Mar. Drugs, 2009, 7, 528│B. K. Rubio, et al, Tet. Lett., 2010, 51, 6718 O HO O

N O N

HO

O

O

N H

O H N

HN

O

N H O

H N

NH O

O

338

1 Peptides

800 Bouillomide B Lyngbyastatin 10 Type: Cyclic depsipeptides with AHP. C49H67BrN8O12 Amorph. solid, [α]D20 = −36° (c = 0.009, MeOH). Source: Cyanobacteria Lyngbya semiplena (Tumon Bay, Guam) and Lyngbya bouillonii (Guam). Pharm: Anticancer-Cell-Effect (model: elastase and chymotrypsin, mechanism: serine proteases inhibition); serine protease selective inhibitor (elastase, IC50 = 1.0 μmol/L; chymotripsin, IC50 = 9.3 μmol/L; trypsin, 100 μmol/L inactive) (Rubio, 2010); serine protease selective inhibitor (elastase, IC50 = 0.12 μmol/L) (Kwan, 2009). Ref: J. C. Kwan, et al, Mar. Drugs, 2009, 7, 528│B. K. Rubio, et al, Tet. Lett., 2010, 51, 6718 Br O HO O

N O

O H N

N

O

O

N H

N H

HN

H N

NH O

O

O

O

HO

801 Cyanopeptolin 954 Type: Cyclic depsipeptides with AHP. C46H63ClN8O12 Amorph. powder. Source: Cyanobacterium Microcystis aeruginosa NIVA Cya 43. Pharm: Chymotrypsin inhibitor. Ref: E. Von Elert, et al, JNP, 2005, 68, 1324 Cl

3'

HO

H N N

O

O

O

HO

N

O

N H

N H

O O

O

O

O

NH2 HN

O

NH

802 Cyanopeptolin 963 A Type: Cyclic depsipeptides with AHP. C49H69N7O13 Amorph. solid. Source: Cyanobacterium Microcystis sp. PCC 7806 Pharm: Chymotrypsin inhibitor. Ref: B. Bister, et al, JNP, 2004, 67, 1755

1.18 Cyclic Depsipeptides with AHP

H N N

O

O

O

O HO

O

O N

O

339

H N

N H O

O

O

NH

N H

OH

OH

803 Dolastatin 13 Type: Cyclic depsipeptides with AHP. C46H63N7O12 Cryst. (CH2Cl2/hexane), mp 286–289 °C, [α]D = +94° (c = 0.01, MeOH). Source: Sea hare Dolabella auricularia. Pharm: Cell growth Inhibitor (PS, ED50 = 0.013 μg/mL). Ref: G. R. Pettit, et al, JACS, 1989, 111. 5015

O

OH

O O N H

N

O

O

O H N

N

H N

HN

O

O NH

O

O

HO

804 Kurahamide Type: Cyclic depsipeptides with AHP. C55H77N9O15 Source: Cyanobacterium Lyngbya sp. [Syn. Moorea sp.] (assemblage, consisting mostly of Lyngbya sp.). Pharm: Proteases elastase inhibitor (strong); chymotrypsin inhibitor (strong). Ref: A. Iwasaki, et al, Bull. Chem. Soc. Jpn., 2014, 87, 609 OH

O

O

N O N

HO

O

O

N H H N

O HN

N H

O

O O

O

O

H N

N H

O H N

O

340

1 Peptides

805 Largamide D Type: Cyclic depsipeptides with AHP. C56H82BrN9O17 Amorph. powder, [α]D20 = −43.5° (c = 0.26, MeOH). Source: Cyanobacteria Lyngbya cf. confervoides and Oscillatoria sp. Pharm: Serine protease inhibitor (chymotrypsin, IC50 = (0.083 ± 0.008)μmol/L, control Molassamide, IC50 = 234 nmol/L; elastase, IC50 = (0.045 ± 0.003)μmol/L, Molassamide, IC50 = 32 nmol/L); chymotrypsin inhibiyor (IC50 = 10 μmol/L). Ref: A. Plaza, et al, JOC, 2006, 71, 6898│S. Matthews, et al, Mar. Drugs, 2010, 8, 1803 Br 3''

N

H N H OH

O HO

OH

O

N

O

HO

O O

O

O NH

N H

O N H

O

HO O

H N O

NH

N H

HO

806 Largamide D oxazolidine Type: Cyclic depsipeptides with AHP. C56H80BrN9O16 Colorless amorphous solid, [α]D20 = −35° (c = 0.1, MeOH). Source: Cyanobacterium Lyngbya cf. confervoides (Port Everglades inlet, Fort Lauderdale, Florida). Pharm: Serine protease inhibitor (chymotrypsin, IC50 = (0.928 ± 0.093)μmol/L, control Molassamide, IC50 = 234 nmol/L; elastase, IC50 = (1.52 ± 0.08)μmol/L, Molassamide, IC50 = 32 nmol/L). Ref: A. Plaza, et al, JOC, 2006, 71, 6898│S. Matthews, et al, Mar. Drugs, 2010, 8, 1803 OH O

O H N

HN O OH O

O N H

H HN N O

N OH O O

N O

N

H N

O

O OH Br OH

1.18 Cyclic Depsipeptides with AHP

341

807 Largamide E Type: Cyclic depsipeptides with AHP. C56H82ClN9O17 Amorph. powder, [α]D20 = −42.7° (c = 0.15, MeOH). Source: Cyanobacterium Oscillatoria sp. Pharm: Anticancer-CellEffect (model: α-chymotrypsin, mechanism: serine protease inhibition); serine protease selective inhibitor (chymotripsin, IC50 = 10.0 μmol/L; trypsin, inactive). Ref: A. Plaza, et al, JOC, 2006, 71, 6898; 2009, 74, 486 HO

Cl N

H N H OH O

O

O HO

N

O

HO

O

O

O

O NH

N H

N H

O

HO O

H N

NH O

N H

HO

808 Largamide F Type: Cyclic depsipeptides with AHP. C59H80BrN9O18 Amorph. powder, [α]D20 = −55° (c = 0.04, MeOH). Source: Cyanobacterium Oscillatoria sp. Pharm: Anticancer-CellEffect (model: α-chymotrypsin, mechanism: serine protease inhibition); serine protease selective inhibitor (chymotripsin, IC50 = 4.0 μmol/L; trypsin, inactive). Ref: A. Plaza, et al, JOC, 2006, 71, 6898; 2009, 74, 486 HO

Br N

HO

H N

O

H OH O

O

O HO

N

O

N H

O

O NH

O N H

O

HO O

H N O

N H

NH

OH HO

809 Largamide G Type: Cyclic depsipeptides with AHP. C60H82BrN9O18 Amorph. powder, [α]D20 = −70° (c = 0.04, MeOH). Source: Cyanobacterium Oscillatoria sp. Pharm: Anticancer-CellEffect (model: α-chymotrypsin, mechanism: serine protease inhibition); serine

342

1 Peptides

protease selective inhibitor (chymotripsin, IC50 = 25.0 μmol/L; trypsin, inactive). Ref: A. Plaza, et al, JOC, 2006, 71, 6898; 2009, 74, 486 HO

Br N

HO

H N

O

H OH O

O

O HO

N

O

O

O

O NH

N H

H N

N H

O

HO O

O

N H

NH

OH HO

810 Lyngbyastatin 4 Type: Cyclic depsipeptides with AHP. C53H68N8O18S Amorph. powder, [α]D20 = +8.4° (c = 0.25, MeOH). Source: Cyanobacterium Lyngbya confervoides. Pharm: AnticancerCell-Effect (model: bovine pancreatic α-chymotrypsin and porcine pancreatic elastase, mechanism: serine protease inhibition); serine protease selective inhibitor (elastase, IC50 = 0.03 μmol/L; chymotripsin, IC50 = 0.30 μmol/L; trypsin, 30 μmol/L inactive); elastase inhibitor; chymotrypsin inhibitor. Ref: S. Matthew, et al, JNP, 2007, 70, 124

HO

O S

O

HO

O OH

H N

N

O O

O HO

N

O N H

O

O

O O

O NH

NH

O N H

NH

OH

811 Lyngbyastatin 5 Type: Cyclic depsipeptides with AHP. C53H68N8O15 Amorph. solid. Source: Cyanobacteria Lyngbya confervoides and Lyngbya spp. (Florida). Pharm: AnticancerCell-Effect (model: porcine pancreatic elastase, mechanism: serine protease inhibition);

1.18 Cyclic Depsipeptides with AHP

343

serine protease selective inhibitor (elastase, IC50 = 3.2 μmol/L; chymotripsin, IC50 = 2.8 μmol/L; trypsin, 30 μmol/L inactive); elastase inhibitor. Ref: K. Taori, et al, JNP, 2007, 70, 1593 OH OH

HO H N N

O O

O

O

O

O

O

O N

HO

O

O

NH

NH

N H NH

N H

OH

812 Lyngbyastatin 6 Type: Cyclic depsipeptides with AHP. C54H70N8O18S Amorph. powder. Source: Cyanobacteria Lyngbya spp. Pharm: Anticancer-Cell-Effect (model: porcine pancreatic elastase, mechanism: serine protease inhibition); serine protease selective inhibitor (elastase, IC50 = 2.0 μmol/L; chymotripsin, IC50 = 2.5 μmol/L; trypsin, 30 μmol/L inactive); elastase inhibitor. Ref: K. Taori, et al, JNP, 2007, 70, 1593 HO HO

O

O

S

O OH

H N

N

O O

O

O

N

O N H

O

O

O

O N H

O O

NH

NH

NH

OH

813 Lyngbyastatin 8 Type: Cyclic depsipeptides with AHP. C47H64N8O12 Amorph. solid, [α]D20 = −4° (c = 0.02, MeOH). Source: Cyanobacterium Lyngbya semiplena. Pharm: AnticancerCell-Effect (model: porcine pancreatic elastase, mechanism: serine protease inhibition);

344

1 Peptides

serine protease selective inhibitor (elastase, IC50 = 0.12 μmol/L). Ref: J. C. Kwan, et al, Mar. Drugs, 2009, 7, 528 OH NH

O

30

O O

O

O O

N H

N O

O H N

N

NH

N H HN

O

O

HO

814 Microviridin A Type: Cyclic depsipeptides with AHP. C85H100N16O24 Amorph. solid, [α]D = +21.7° (c = 0.95, MeOH). Source: Cyanobacterium Microcystis viridis. Pharm: Tyrosinase inhibitor. Ref: M. O. Ishitsuka, et al, JACS, 1990, 112, 8180

NH OH

O H

N H H O N

O O H N H

H N O

O N H

H N O

O HO

HN

H O

NH N H

O

H

H

O

O HN

H

O

NH H

O HN

H N

OH O O

H

H N H

COOH

O O

N H

O

H

815 Microviridin B Type: Cyclic depsipeptides with AHP. C84H106N16O24 Amorph. powder, [α]D23 = +153° (c = 0.1, MeOH). Source: Cyanobacterium Microcystis aeruginosa NIES-298. Pharm: Elastase inhibitor. Ref: T. Okino, et al, Tetrahedron, 1995, 51, 10679

1.18 Cyclic Depsipeptides with AHP

345

H N O H N

O O H N H

H N

N H

O

O

H N

O

H

HO

O

NH

OH

O

OH

O

O N H

O

NH HN

O O O

N

NH

NH

N H

COOH

N H

H

OO N H

O O

O

H

816 Microviridin C Type: Cyclic depsipeptides with AHP. C85H110N16O25 Amorph. powder, [α]D23 = −2° (c = 0.06, MeOH). Source: Cyanobacterium Microcystis aeruginosa NIES-298 Pharm: Elastase inhibitor. Ref: T. Okino, et al, Tetrahedron, 1995, 51, 10679

H N O H N

O O H N H

H N O

OH

O N H

O

H N

O

H

HO

O

O N

NH OO N H

O N H

OH NH

NH

OH

O HN

O O O

H NH

N H

O O N H

COOH

O

H

817 Microviridin D Type: Cyclic depsipeptides with AHP. C84H107N17O26S Amorph. powder, [α]D = +66° (c = 0.1, MeOH). Source: Cyanobacteria Oscillatoria agardhii NIES 204 and NIES 26 (freshwater). Pharm: Serine protease inhibitor. Ref: H. J. Shin, et al, Tetrahedron, 1996, 52, 8159│M. Murakami, et al, Phytochemistry, 1997, 45, 1197

346

1 Peptides

H N OH

O O

O H N H

NH2

O

H N

N H

O

O

H N

O H N

O

H

HO

O

O N H

O

OH NH

NH

H

OO

NH

N H

N H

S

OH

HN

O O O

N

NH

O

O O N H

COOH

O

818 Microviridin E Type: Cyclic depsipeptides with AHP. C82H100N14O24 Amorph. powder, [α]D20 = +12° (c = 0.1, MeOH). Source: Cyanobacteria Oscillatoria agardhii NIES 204 and NIES 26 (freshwater). Pharm: Serine protease inhibitor. Ref: H. J. Shin, et al, Tetrahedron, 1996, 52, 8159│M. Murakami, et al, Phytochemistry, 1997, 45, 1197 O HN

O

O HO O N H

H N O H O

NH N

OO HN H HO

O OH

O

HO NH

N H

NH

O

NH

O

OO HN

O N H

H N H

O O N H

COOH

O

819 Molassamide Type: Cyclic depsipeptides with AHP. C48H66N8O13 Amorph. powder, [α]D25 = −2.7° (c = 0.21, MeOH). Source: Cyanobacterium Dichothrix utahensis. Pharm: AnticancerCell-Effect (model: bovine pancreatic α-chymotrypsin and porcine pancreatic elastase, mechanism: serine protease inhibition); serine protease selective inhibitor (elastase, IC50 = 0.032 μmol/L; chymotripsin, IC50 = 0.234 μmol/L; trypsin, 10 μmol/L inactive). Ref: S. P. Gunasekera, et al, JNP, 2010, 73, 459

1.18 Cyclic Depsipeptides with AHP

347

HO

H N

N O

O HO

O O

O

N

O

O

O

N H H

NH

N H

O

H N

N H

O

HO

820 Oscillapeptin A Type: Cyclic depsipeptides with AHP. C56H77N7O18S Amorph. powder, [α]D20 = −31.5° (c = 0.18, MeOH). Source: Cyanobacterium Oscillatoria agardhii NIES 204 (freshwater). Pharm: Chymotrypsin inhibitor (IC50 = 2.2 μg/mL); elastase inhibitor (IC50 = 0.3 μg/mL). Ref: H. J. Shin, et al, Tet. Lett., 1995, 36, 5235│Y. Itou, et al, Tetrahedron, 1999, 55, 6871 O

H N N

O H

O O HO

H

N

O N H

O O

O N H

O NH

O

H N O

O

O S OH O

OH OH

821 Oscillapeptin B Type: Cyclic depsipeptides with AHP. C57H79N7O18S Powder, [α]D = −30.2° (c = 0.2, MeOH). Source: Cyanobacterium Oscillatoria agardhii NIES 204 (freshwater). Pharm: Chymotrypsin inhibitor (IC50 = 2.1 μg/mL); elastase inhibitor (IC50 = 0.05 μg/mL). Ref: H. J. Shin, et al, Tet. Lett., 1995, 36, 5235│Y. Itou, et al, Tetrahedron, 1999, 55, 6871

348

1 Peptides

O

H N N

O H

O O HO

H

O O

O

N

O N H

O

O

O

NH

N H

O

H N

O S OH O

OH OH

822 Oscillapeptin C Type: Cyclic depsipeptides with AHP. C55H79N7O14 Powder, [α]D = −26.6° (c = 0.05, MeOH). Source: Cyanobacterium Oscillatoria agardhii NIES 205 (freshwater). Pharm: Chymotrypsin inhibitor (IC50 = 3.0 μg/mL). Ref: Y. Itou, et al, Tetrahedron, 1999, 55, 6871

O O O HN O N H

H

O O O

O

11

28

N H NH H

N H

OH

O

O

N

O

H N

49 52

OH

OH

823 Oscillapeptin D Type: Cyclic depsipeptides with AHP. C54H77N7O17S Powder, [α]D = −23.4° (c = 0.05, MeOH). Source: Cyanobacterium Oscillatoria agardhii NIES 205 (freshwater). Pharm: Chymotrypsin inhibitor (IC50 = 2.2 μg/mL); elastase inhibitor (IC50 = 30 μg/mL). Ref: Y. Itou, et al, Tetrahedron, 1999, 55, 6871

1.18 Cyclic Depsipeptides with AHP

H N N

H

O H

O

O

O

O HO

N

O

11

349

O

N H

O

28

O

O

NH

N H

O

H N

H

O S OH O

49 52

OH OH

824 Oscillapeptin E Type: Cyclic depsipeptides with AHP. C55H75N7O17S Powder, [α]D = −25.1° (c = 0.05, MeOH). Source: Cyanobacterium Oscillatoria agardhii NIES 205 (freshwater). Pharm: Chymotrypsin inhibitor (IC50 = 3.0 μg/mL); elastase inhibitor (IC50 = 3.0 μg/mL). Ref: H. J. Shin, et al, Tet. Lett., 1995, 36, 5235│Y. Itou, et al, Tetrahedron, 1999, 55, 6871

H N N

O H

O O HO

H

N

O N H

O O

O N H

O

O

H N O

NH

O

O S

OH

O

OH OH

825 Oscillapeptin F Type: Cyclic depsipeptides with AHP. C51H76N8O16S Powder, [α]D = −56.1° (c = 1, MeOH). Source: Cyanobacterium Oscillatoria agardhii NIES 596 (freshwater). Pharm: Trypsin inhibitor (IC50 = 0.2 μg/mL); plasmin inhibitor (IC50 = 0.03 μg/mL). Ref: Y. Itou, et al, Tetrahedron, 1999, 55, 6871

350

1 Peptides

H N N

O H

H

O

O

O

O HO

O

N

O

N H

O

O

H N

N H

O

O

NH

O S

OH

O NH2 OH

826 Oscillapeptin J Type: Cyclic depsipeptides with AHP. C47H68N10O18S Amorph. powder. Source: Cyanobacterium Planktothrix rubescens (freshwater). Pharm: Toxin (crustaceans). Ref: J. F. Blom, et al, JNP, 2003, 66, 431 OH

H N N

OH

O H

O O HO

H

N

O

O

O

O

N H

O

OH

H N O

NH

O

N H

O S

OH

O NH N H

OH NH2

827 Salinamide A Type: Cyclic depsipeptides with AHP. C51H69N7O15 Pale yellow solid, mp 221–225 °C (dec), [α]D = −26° (c = 0.97, CDCl3). Source: Marine-derived streptomycete Streptomyces sp. CNB-091 from scyphomedusa Cassiopeia xamachana (surface, Florida Keys). Pharm: Anti-inflammatory; antibacterial (gram-positive bacteria Streptococcus pneumonia and Staphylococcus pyrogenes, MIC = 4 μg/mL). Ref: J. A. Trischman, et al, JACS, 1994, 116, 757│B. S. Moore, et al, JOC, 1999, 64, 1145

1.18 Cyclic Depsipeptides with AHP

351

HO O O

OH O HN

O N

O O

O

O

N H

HN

Ph O

H N

O

NH O

N H O O

828 Salinamide B Type: Cyclic depsipeptides with AHP. C51H70ClN7O15 Cryst., mp 239–241 °C (melt), [α]D = −65° (c = 0.57, CDCl3). Source: Marine-derived streptomycete Streptomyces sp. CNB-091 from scyphomedusa Cassiopeia xamachana (surface, Florida Keys). Pharm: Anti-inflammatory; antibacterial (gram-positive bacteria Streptococcus pneumoniae, MIC = 4 μg/mL, Staphylococcus pyrogenes, MIC = 2 μg/mL). Ref: J. A. Trischman, et al, JACS, 1994, 116, 757│B. S. Moore, et al, JOC, 1999, 64, 1145 HO O O

OH O HN

O

N H

HN

O N

O O

O

H N

Ph O

NH O

N H

Cl O O

OH

829 Somamide A Type: Cyclic depsipeptides with AHP. C48H67N7O12S Oil, [α]D22 = −2.5° (c = 0.08, MeOH). Source: Cyanobacteria Lyngbya majuscula and Schizothrix sp. (assemblage, Fiji). Pharm: Antibiotic. Ref: L. M. Nogle, et al, JNP, 2001, 64, 716

352

1 Peptides

OH

O

O

N

O

O

N H

O HN

H N

N

H N

O

N H

O

O O

O

HO

S

830 Somamide B Type: Cyclic depsipeptides with AHP. C46H62N8O12 Oil, [α]D22 = −19.2° (c = 0.05, MeOH). Source: Cyanobacteria Lyngbya majuscula and Schizothrix sp. (assemblage). Pharm: Serine protease selective inhibitor (elastase, IC50 = 9.5 μmol/L; chymotripsin, IC50 = 4.2 μmol/L; trypsin, 30 μmol/L inactive). Ref: L. M. Nogle, et al, JNP, 2001, 64, 716│K. Taori, et al, JNP, 2007, 70, 1593 OH

O

O

N

O

O

N H

O HN

H N

N

H N

O

N H

O

O O

O

HO

NH2

831 Tasipeptin A Type: Cyclic depsipeptides with AHP. C45H71N7O10 Amorph. powder, [α]D24 = −23° (c = 1.5, MeOH). Source: Cyanobacterium Symploca sp. NIH304 (Palau, Oceania). Pharm: Cytotoxic (KB, IC50 = 0.93 μmol/L). Ref: P. G. Williams, et al, JNP, 2003, 66, 620

H N

O

N O

O

O

O O HO

N

O N H

N H

O NH

H N O

1.18 Cyclic Depsipeptides with AHP

353

832 Tasipeptin B Type: Cyclic depsipeptides with AHP. C40H62N6O9 Amorph. powder, [α]D21 = −13° (c = 0.7, MeOH). Source: Cyanobacterium Symploca sp. NIH304 (Palau, Oceania). Pharm: Cytotoxic (KB, IC50 = 0.82 μmol/L). Ref: P. G. Williams, et al, JNP, 2003, 66, 620

H N

O

N O

O

O

O O HO

N

O

N H

O NH

N H

833 Vitilevuamide Type: Cyclic depsipeptides with AHP. C77H114N14O21S Amorph. solid. Source: Ascidians Didemnum cucculiferum and Polysyncraton lithostrotum. Pharm: Anticancer-Cell-Effect (MMOA: Inhibits polymn. of tubulin dimers to microtubules). Ref: Pat. Coop. Treaty (WIPO), 1998, 98 13 063│A. M. Fernandez, et al., Pure Appl. Chem., 1998, 70, 2130│M. C. Edler, et al., Biochem. Pharmacol., 2002, 63, 707 H N NH

O

H N

O O O

HN

O

OH

NH O

O

O

N H

N S

OH

O O

O

HN

NH

OH O

O

O HN

H N O

O H N

O

O N H

N

354

1 Peptides

1.19 Depsipeptides with Pyridazine 834 Pandanamide B Type: Depsipeptides with pyridazine. C31H46N6O9 Source: Marine-derived streptomycete Streptomyces sp. (sediment, Padana Nahua, Papua New Guinea). Pharm: Cytotoxic (JurKat-T lymphocyte cells). Ref: D. E. Williams, et al, Org. Lett., 2011, 13, 3936

HN

O

H N O

H N

N O

O

OH

O

O

H N

O

N H

HO

835 Piperazimycin A Type: Depsipeptides with pyridazine. C31H47ClN8O10 Amorph. powder, [α]D = −45° (c = 0.3, CHCl3). Source: Marine-derived streptomycete Streptomyces sp. CNQ-593 and Act8015. Pharm: Cytotoxic (monolayer proliferation assay: bladder BXF-1218L, IC50 = 0.113 μg/mL, IC70 = 0.176 μg/mL; BXF-T24, IC50 = 0.098 μg/mL, IC70 = 0.159 μg/mL; glioblastoma CNXF-498NL, IC50 = 0.088 μg/mL, IC70 = 0.149 μg/mL; CNXF-SF268, IC50 = 0.097 μg/mL, IC70 = 0.156 μg/mL; colon CXF-HCT116, IC50 = 0.105 μg/mL, IC70 = 0.163 μg/mL; CXF-HT29, IC50 = 0.098 μg/mL, IC70 = 0.154 μg/mL; stomach GXF-251L, IC50 = 0.123 μg/mL, IC70 = 0.201 μg/mL; head and neck HNXF-536L, IC50 = 0.871 μg/mL, IC70 = 1.405 μg/mL; lung LXF-1121L, IC50 = 0.105 μg/mL, IC70 = 0.167 μg/mL; LXF-289L, IC50 = 0.117 μg/mL, IC70 = 0.187 μg/mL; LXF-526L, IC50 = 0.123 μg/mL, IC70 = 0.190 μg/mL; LXF-529L, IC50 = 0.103 μg/mL, IC70 = 0.167 μg/mL; LXF-629L, IC50 = 0.102 μg/mL, IC70 = 0.166 μg/mL; LXF-H460, IC50 = 0.098 μg/mL, IC70 = 0.154 μg/mL; breast MAXF401NL, IC50 = 0.110 μg/mL, IC70 = 0.177 μg/mL; MAXF-MCF7, IC50 = 0.103 μg/mL, IC70 = 0.165 μg/mL; melanoma MEXF-276L, IC50 = 0.127 μg/mL, IC70 = 0.207 μg/mL; MEXF-394NL, IC50 = 0.098 μg/mL, IC70 = 0.158 μg/mL; MEXF-462NL, IC50 = 0.107 μg/mL, IC70 = 0.175 μg/mL; MEXF-514L, IC50 = 0.125 μg/mL, IC70 = 0.186 μg/mL; MEXF-520L, IC50 = 0.111 μg/mL, IC70 = 0.182 μg/mL; ovary OVXF-1619L, IC50 = 0.127 μg/mL, IC70 = 0.202 μg/mL; OVXF-899L, IC50 = 1.102 μg/mL, IC70 = 1.818 μg/mL; OVXF-OVCAR3, IC50 = 0.113 μg/mL, IC70 = 0.184 μg/mL; pancreas PAXF-1657L, IC50 = 0.125 μg/mL, IC70 = 0.212 μg/mL; PAXF-PANC1, IC50 = 0.100 μg/mL, IC70 = 0.163 μg/mL; prostate PRXF-22RV1, IC50 = 0.092 μg/mL, IC70 = 0.157 μg/mL; PRXF-DU145, IC50 = 0.105 μg/mL, IC70 = 0.163 μg/mL; PRXF-LNCAP, IC50 = 0.118 μg/mL, IC70 = 0.176 μg/mL; PRXF-PC3M, IC50 = 0.099 μg/mL, IC70 = 0.157 μg/mL; mesothelioma PXF-1752L, IC50 = 0.110 μg/mL, IC70 = 0.173 μg/mL; kidney RXF-1781L,

1.19 Depsipeptides with Pyridazine

355

IC50 = 0.143 μg/mL, IC70 = 0.252 μg/mL; RXF-393NL, IC50 = 0.103 μg/mL, IC70 = 0.163 μg/mL; RXF-486L, IC50 = 1.129 μg/mL, IC70 = 1.798 μg/mL; RXF-944L, IC50 = 0.096 μg/mL, IC70 = 0.161 μg/mL; uterus UXF-1138L, IC50 = 0.101 μg/mL, IC70 = 0.162 μg/mL; mean IC50 = 0.130 μg/mL, mean IC70 = 0.210 μg/mL); toxic (brine shrimp microwell assay, 10 μg/mL, mortality rate 20%); antibacterial (agar diffusion assay, 40 μg/disc (diameter 9 mm), Bacillus subtilis, IZD = 14 mm; Staphylococcus aureus, IZD = 22 mm; Streptomyces viridochromogenes (Tü 57), IZD = 26 mm; Escherichia coli, IZD = 17 mm; Mucor miehei, IZD = 15 mm). Ref: E. D. Miller, et al, JOC, 2007, 72, 323│K. A. Shaaban, et al, J. Antibiot., 2008, 61, 736 HO

NH N

HN

O O

HN

OH

O O O

N

O O

NH

N HN

8

OH

Cl

836 Piperazimycin B Type: Depsipeptides with pyridazine. C31H47ClN8O9 Amorph. powder, [α]D = −91° (c = 0.08, CHCl3). Source: Marine-derived streptomycetes Streptomyces sp. CNQ-593 and Act8015. Pharm: Antibacterial (agar diffusion assay, 40 μg/disc (diameter 9 mm), Bacillus subtilis, IZD = 14 mm; Staphylococcus aureus, IZD = 21 mm; Streptomyces viridochromogenes, IZD = 25 mm; Escherichia coli, IZD = 16 mm; Mucor miehei, IZD = 15 mm); antifungal (agar diffusion assay, 40 μg/disc (diameter 9 mm), Candida albicans, IZD = 14 mm); anti-microalgal (agar diffusion assay, 40 μg/disc (diameter 9 mm), Chlorella vulgaris, IZD = 16 mm; Chlorella sorokiniana, IZD = 14 mm; Scenedesmus subspicatus, IZD = 0 mm; Rhizoctonia solani, active; Pythium ultimum, high active). Ref: E. D. Miller, et al, JOC, 2007, 72, 323│K. A. Shaaban, et al, J. Antibiot., 2008, 61, 736 H N

HO O

O

8

O HN

N

N NH

O O

O O

N H HO

Cl N N H

356

1 Peptides

1.20 Monocyclic β-Lactams 837 Monamphilectine A Type: Monocyclic β-lactams. C26H39N3O2 Yellowish oil, [α]D20 = −105.9° (c = 0.34, CHCl3). Source: Sponge Hymeniacidon sp. (Mona I., Puerto Rico, (W67°53′22′′ N18° 52′12′′)). Pharm: Antimalarial (potent). Ref: S. J. Wratten, et al, Tet. Lett., 1978, 4345│E. Aviles, et al, Org. Lett., 2010, 12, 5290 H N

O N O

H H

H NC

1.21 Lipopeptides 838 Gageostatin A Type: Lipopeptides. C52H93N7O14 Amorphous solid, [α]D27 = +52° (c = 0.1, MeOH). Source: Marine-derived bacterium Bacillus subtilis (sediment, Korea waters). Pharm: Antifungal (Rhizoctonia solani, MIC = 4 μg/mL, control Amphotericin B, MIC = 1 μg/mL; Colletotrichum acutatum, MIC = 8 μg/mL, Amphotericin B, MIC = 1 μg/mL; Botrytis cinera, MIC = 4 μg/mL; Amphotericin B, MIC = 1 μg/mL); antifungal (mixture of Gageostatin A+Gageostatin B: Rhizoctonia solani, MIC = 4 μg/mL; Colletotrichum acutatum, MIC = 4 μg/mL; Botrytis cinera, MIC = 4 μg/mL); antibacterial (mixture of Gageostatin A+Gageostatin B: gram-positive bacteria: Staphylococcus aureus, MIC = 8 μg/mL, Bacillus subtilis, MIC = 16 μg/mL; gramnegative bacteria: Salmonella typhi, MIC = 32 μg/mL, Pseudomonas aeruginosa, MIC = 8 μg/mL); antibacterial (gram-positive bacteria: Staphylococcus aureus, MIC = 16 μg/mL, control Azithromycin, MIC = 2 μg/mL, Bacillus subtilis, MIC = 16 μg/mL, Azithromycin, MIC = 2 μg/mL; gram-negative bacteria: Salmonella typhi, MIC = 16 μg/mL, Azithromycin, MIC = 2 μg/mL, Pseudomonas aeruginosa, MIC = 16 μg/mL, Azithromycin, MIC = 2 μg/mL); cytotoxic (MDA-MB-231, GI50 = 14.9 μg/mL, control Adriamycin, GI50 = 0.56 μg/mL; HCT15, GI50 = 11.4 μg/mL, Adriamycin, GI50 = 0.33 μg/mL; PC3, GI50 = 10.8 μg/mL, Adriamycin, GI50 = 0.91 μg/mL; NCI-H23, GI50 = 11.2 μg/mL, Adriamycin, GI50 = 0.71 μg/mL; NUGC-3, GI50 = 11.8 μg/mL, Adriamycin, GI50 = 0.53 μg/mL; ACHN, GI50 = 11.5 μg/mL, Adriamycin, GI50 = 0.51 μg/mL). Ref: F. S. Tareq, et al, Mar. Drugs, 2014, 12, 871

1.21 Lipopeptides

O

357

OH

O O HO O

HO

O

H N

N H

N H

O

O

H N

N H

O

OH

O

H N

N H

O

7

839 Gageostatin B Type: Lipopeptides. C53H95N7O14 Amorphous solid, [α]D27 = +53° (c = 0.1, MeOH). Source: Marine-derived bacterium Bacillus subtilis (sediment, Korea waters). Pharm: Antifungal (Rhizoctonia solani, MIC = 8 μg/mL, control Amphotericin B, MIC = 1 μg/mL; Colletotrichum acutatum, MIC = 8 μg/mL, Amphotericin B, MIC = 1 μg/mL; Botrytis cinera, MIC = 8 μg/mL; Amphotericin B, MIC = 1 μg/mL); antibacterial (gram-positive bacteria: Staphylococcus aureus, MIC = 16 μg/mL, control Azithromycin, MIC = 2 μg/mL, Bacillus subtilis, MIC = 32 μg/mL, Azithromycin, MIC = 2 μg/mL; gram-negative bacteria: Salmonella typhi, MIC = 32 μg/mL, Azithromycin, MIC = 2 μg/mL, Pseudomonas aeruginosa, MIC = 16 μg/mL, Azithromycin, MIC = 2 μg/mL); cytotoxic (MDA-MB-231, GI50 = 16.1 μg/mL, control Adriamycin, GI50 = 0.56 μg/mL; HCT15, GI50 = 18.3 μg/mL, Adriamycin, GI50 = 0.33 μg/mL; PC3, GI50 = 19.4 μg/mL, Adriamycin, GI50 = 0.91 μg/mL; NCI-H23, GI50 = 11.7 μg/mL, Adriamycin, GI50 = 0.71 μg/mL; NUGC-3, GI50 = 13.9 μg/mL, Adriamycin, GI50 = 0.53 μg/mL; ACHN, GI50 = 18.4 μg/mL, Adriamycin, GI50 = 0.51 μg/mL); cytotoxic (mixture of Gageostatin A+Gageostatin B: MDA-MB-231, GI50 = 10.5 μg/mL; HCT15, GI50 = 10.9 μg/mL; PC3, GI50 = 12.0 μg/mL; NCI-H23, GI50 = 4.6 μg/mL, significant activity; NUGC-3, GI50 = 10.1 μg/mL; ACHN, GI50 = 10.7 μg/mL). Ref: F. S. Tareq, et al, Mar. Drugs, 2014, 12, 871 OH

O O O HO O

N H

HO

O

H N O

N H

O

H N O

N H

O

H N O

N H

OH 5

840 Gageostatin C Type: Lipopeptides. C51H89N7O13 Amorphous solid, [α]D27 = +16° (c = 0.1, MeOH). Source: Marine-derived bacterium Bacillus subtilis (sediment, Korea waters). Pharm: Antifungal (Rhizoctonia solani, MIC = 32 μg/mL, control Amphotericin B, MIC = 1 μg/mL; Colletotrichum acutatum, MIC = 16 μg/mL, Amphotericin B, MIC = 1 μg/mL; Botrytis cinera, MIC = 32 μg/mL; Amphotericin B, MIC = 1 μg/mL); antibacterial (gram-positive bacteria: Staphylococcus aureus, MIC = 64 μg/mL,

358

1 Peptides

control Azithromycin, MIC = 2 μg/mL, Bacillus subtilis, MIC = 32 μg/mL, Azithromycin, MIC = 2 μg/mL; gram-negative bacteria: Salmonella typhi, MIC = 32 μg/mL, Azithromycin, MIC = 2 μg/mL, Pseudomonas aeruginosa, MIC = 64 μg/mL, Azithromycin, MIC = 2 μg/mL); cytotoxic (MDA-MB-231, GI50 = 11.2 μg/mL, control Adriamycin, GI50 = 0.56 μg/mL; HCT15, GI50 = 23.2 μg/mL, Adriamycin, GI50 = 0.33 μg/mL; PC3, GI50 = 11.7 μg/mL, Adriamycin, GI50 = 0.91 μg/mL; NCI-H23, GI50 = 10.9 μg/mL, Adriamycin, GI50 = 0.71 μg/mL; NUGC-3, GI50 = 10.5 μg/mL, Adriamycin, GI50 = 0.53 μg/mL; ACHN, GI50 = 12.3 μg/mL, Adriamycin, GI50 = 0.51 μg/mL). Ref: F. S. Tareq, et al, Mar. Drugs, 2014, 12, 871

O HO

N H

O

OH

O

O HO H N

O N H

O

O

H N O

N H

O

H N O

N H

3

841 Gageotetrin A Type: Lipopeptides. C25H46N2O7 Amorphous solid. Source: Marine-derived bacterium Bacillus subtilis (sediment, Korea waters). Pharm: Antibacterial (Staphylococcus aureus, MIC = 0.03 μmol/L; Bacillus subtilis, MIC = 0.03 μmol/L; Salmonella typhi, MIC = 0.06 μmol/L; Pseudomonas aeruginosa, MIC = 0.06 μmol/L; control Azithromycin, all MICs = 0.01 μmol/L); antifungal (Rhizoctonia solani, MIC = 0.06 μmol/L; Colletotrichum acutatum, MIC = 0.03 μmol/L; Botrytis cinera, MIC = 0.03 μmol/L; control Amphotericin B, all MICs = 0.01 μmol/L). Ref: F. S. Tareq, et al, Org. Lett., 2014, 16, 928 O

OH

O HO

HTDA

Glu

Leu

O

H N O

N H

OH 7

842 Gageotetrin B Type: Lipopeptides. C39H72N4O8 Amorphous solid. Source: Marine-derived bacterium Bacillus subtilis (sediment, Korea waters). Pharm: Antibacterial (Staphylococcus aureus, MIC = 0.04 μmol/L; Bacillus subtilis, MIC = 0.02 μmol/L; Salmonella typhi, MIC = 0.02 μmol/L; Pseudomonas aeruginosa, MIC = 0.04 μmol/L; control Azithromycin, all MICs = 0.01 μmol/L); antifungal (Rhizoctonia solani, MIC = 0.02 μmol/L; Colletotrichum acutatum, MIC = 0.01 μmol/L; Botrytis cinera, MIC = 0.01 μmol/L; control Amphotericin B, all MICs = 0.01 μmol/L) motility inhibition and lytic activities (zoospores of Phytophthora capsici, 0.02 μmol/L, motility inhibition: 15 min, InRt = 55%, 30 min, InRt = 65%, 45 min, InRt = 75%, 60 min, InRt = 100%; lytic activity). Ref: F. S. Tareq, et al, Org. Lett., 2014, 16, 928

1.21 Lipopeptides

O

O O

Leu1

Leu2

H N O

O

Leu3

OMeGlu

OH

O

H N

N H

359

N H

O

7

843 Gageotetrin C Type: Lipopeptides. C38H70N4O8 Amorphous solid. Source: Marine-derived bacterium Bacillus subtilis (sediment, Korea waters). Pharm: Antibacterial (Staphylococcus aureus, MIC = 0.04 μmol/L; Bacillus subtilis, MIC = 0.04 μmol/L; Salmonella typhi, MIC = 0.02 μmol/L; Pseudomonas aeruginosa, MIC = 0.02 μmol/L; control Azithromycin, all MICs = 0.01 μmol/L); antifungal (Rhizoctonia solani, MIC = 0.02 μmol/L; Colletotrichum acutatum, MIC = 0.02 μmol/L; Botrytis cinera, MIC = 0.01 μmol/L; control Amphotericin B, all MICs = 0.01 μmol/L); motility inhibition and lytic activities (zoospores of Phytophthora capsici, 0.02 μmol/L, motility inhibition: 30 min, InRt = 40%, 45 min, InRt = 60%, 60 min, InRt = 70%; failed to lyse zoospores). Ref: F. S. Tareq, et al, Org. Lett., 2014, 16, 928 O Leu2

Leu1

O

O

H N

Glu

HDDA

OH

O

H N

N H

O

OH

Leu3

N H

O

4

844 Ggeopeptide A Type: Lipopeptides. C37H68N4O9 Amorphous solid, [α]D27 = −21° (c = 0.1, MeOH). Source: Marine-derived bacterium Bacillus subtilis (sediment, Korea waters). Pharm: Antifungal (pathogenic fungi Rhizoctonia solani, Botrytis cinerea, and Colletotrichum acutatum, MIC = 0.02–0.06 μmol/L, significant, promising candidates for development of non-cytotoxic antifungal agents); motility inhibition and lytic activities (zoospores of late blight pathogen Phytophthora capsici, significant); antibacterial (gram-positive and -negative bacteria, MIC = 0.04–0.08 μmol/L, potent). Ref: F. S. Tareq, et al, J. Agric. Food Chem., 2014, 62, 5565

O HO

O

H N O

N H

O

O

H N O

OH

N H

OH 7

360

1 Peptides

845 Ggeopeptide B Type: Lipopeptides. C39H72N4O9 Amorphous solid, [α]D27 = −40° (c = 0.1, MeOH). Source: Marine-derived bacterium Bacillus subtilis (sediment, Korea waters). Pharm: Antifungal (pathogenic fungi Rhizoctonia solani, Botrytis cinerea, and Colletotrichum acutatum, MIC = 0.02–0.06 μmol/L, significant, promising candidates for development of non-cytotoxic antifungal agents); motility inhibition and lytic activities (zoospores of late blight pathogen Phytophthora capsici, significant); antibacterial (gram-positive and -negative bacteria, MIC = 0.04–0.08 μmol/L, potent). Ref: F. S. Tareq, et al, J. Agric. Food Chem., 2014, 62, 5565 O

O

O

O H N

HO

O

O H N

N H

OH

N H

O

8

846 Ggeopeptide C Type: Lipopeptides. C37H68N4O9 Amorphous solid, [α]D27 = −20° (c = 0.1, MeOH). Source: Marine-derived bacterium Bacillus subtilis (sediment, Korea waters). Pharm: Antifungal (pathogenic fungi Rhizoctonia solani, Botrytis cinerea, and Colletotrichum acutatum, MIC = 0.02–0.06 μmol/L, significant, promising candidates for development of non-cytotoxic antifungal agents); motility inhibition and lytic activities (zoospores of late blight pathogen Phytophthora capsici, significant); antibacterial (gram-positive and -negative bacteria, MIC = 0.04–0.08 μmol/L, potent). Ref: F. S. Tareq, et al, J. Agric. Food Chem., 2014, 62, 5565

O HO

O

H N O

N H

O

O

H N O

N H

OH 4

OH

847 Ggeopeptide D Type: Lipopeptides. C38H70N4O9 Amorphous solid, [α]D27 = −70° (c = 0.05, MeOH). Source: Marine-derived bacterium Bacillus subtilis (sediment, Korea waters). Pharm: Antifungal (pathogenic fungi Rhizoctonia solani, Botrytis cinerea, and Colletotrichum acutatum, MIC = 0.02–0.06 μmol/L, significant, promising candidates for development of non-cytotoxic antifungal agents); motility inhibition and

1.21 Lipopeptides

361

lytic activities (zoospores of late blight pathogen Phytophthora capsici, significant); antibacterial (gram-positive and -negative bacteria, MIC = 0.04–0.08 μmol/L, potent). Ref: F. S. Tareq, et al, J. Agric. Food Chem., 2014, 62, 5565

O

O

H N

HO

N H

O

O

H N

N H

O

O

OH 5

OH

848 Kurahyne Type: Lipopeptides. C47H78N6O7 Source: Cyanobacterium Lyngbya sp. [Syn. Moorea sp.] (assemblage, consisting mostly of Lyngbya sp.). Pharm: Cytotoxic (HeLa, inhibitor of the cell line and inducer of apoptosis). Ref: A. Iwasaki, et al, RSC Adv., 2014, 4, 12840

O

O N

N

N

N

N O

O

O

O

N

O

849 Mojavensin A Type: Lipopeptides. C50H77N13O14 Source: Marine-derived bacterium Bacillus mojavensis from oyster Pinctada martensii (Weizhou I., Guangxi, China). Pharm: Antifungal. Ref: Z. Ma, et al, J. Antibiot., 2012, 65, 317

6

H N

HN

NH2

O

H 2N

O O

O

HN

NH

O OH

O H2 N

H N

O

O

O O

NH O

H N

N

NH2 O

O

NH2

362

1 Peptides

850 Mollemycin A Type: Lipopeptides. C59H96N8O24 Source: Marine-derived streptomycete Streptomyces sp. (sediment, South Molle I., Queensland, Australia). Pharm: Antibacterial (certain gram-positive and -negative bacteria), antiplasmodial (DSPF and MDRPF clones, extremely potent). Ref: R. Raju, et al, Org. Lett., 2014, 16, 1716

HO O

O O

O

O N

O

NH

OH

HO N

O

O

N

N H

O

N

O O

N O

OH OH

H N

OH

O O

O

O O OH

851 Peptidolipin B Type: Lipopeptides. C59H107N7O11 Source: Marine-derived actinomycete Nocardia sp. from ascidian Trididemnum orbiculatum (Florida Keys). Pharm: Antibacterial (MRSA and MSSA, modest). Ref: T. P. Wyche, et al, JNP, 2012, 75, 735

O O

O

N H

O

HO N H

O

H N

N H

O 21

O

H N O

N

O N H

O

1.21 Lipopeptides

363

852 Peptidolipin D Type: Lipopeptides. C63H115N7O11 Source: Marine-derived actinomycete Nocardia sp. from ascidian Trididemnum orbiculatum (Florida Keys). Pharm: Antibacterial (MRSA and MSSA, moderate). Ref: T. P. Wyche, et al, JNP, 2012, 75, 735

O O

O

N H

O

HO N H

O

H N

N H

O 25

O

N

O

H N

N H

O

O

853 Viridamide A Type: Lipopeptides. C46H79N5O10 Oil, [α]D = −107.4° (c = 0.05, CHCl3). Source: Cyanobacterium Oscillatoria nigroviridis OSC3L. Pharm: Antitrypanosomal (Trypanosoma cruzi, IC50 = 1.1–1.5 μmol/L); antileishmanial (Leishmania mexicana, IC50 = 1.1–1.5 μmol/L); antiplasmodial (Plasmodium falciparum). Ref: T. L. Simmons, et al, JNP, 2008, 71, 1544│A. M. S. Mayer et al, Comparative Biochemistry and Physiology, Part C 153, 2011, 191 (rev)

O N

H H N O

O

O N H

N O

O O

O N

O

H

O

854 Viridamide B Type: Lipopeptides. C45H77N5O10 Oil, [α]D = −98° (c = 0.1, CHCl3). Source: Cyanobacterium Oscillatoria nigroviridis OSC3L. Pharm: Antitrypanosomal (Trypanosoma cruzi, IC50 = 1.1–1.5 μmol/L); antileishmanial (Leishmania mexicana, IC50 = 1.1–1.5 μmol/L); antiplasmodial (Plasmodium falciparum). Ref: T. L. Simmons, et al, JNP, 2008, 71, 1544│A. M. S. Mayer et al, Comparative Biochemistry and Physiology, Part C 153, 2011, 191 (rev)

364

1 Peptides

O N

O

O

H H N

N

N H

O

O

O

O O N

O

H

O

1.22 Lipopeptides with Thiazole 855 Hoiamide C Type: Lipopeptides with thiazole. C37H62N4O7S3 Source: Cyanobacteria Lyngbya majuscula and Phormidium gracile (assemblage, reef wall near Pigeon I., Papua New Guinea). Pharm: Toxic (brine shrimp, LC50 = 1.3 μmol/L). Ref: H. Choi, et al, JNP, 2010, 73, 1411 S S

S

N N

N

H N

HO

O

O

O OH

O

OH

856 Lyngbyabellin N Type: Lipopeptides with thiazole. C40H58Cl2N4O11S2 Source: Cyanobacterium Moorea bouillonii (Strawn I., Palmyra Atoll, Central Pacific Ocean). Pharm: Cytotoxic (HCT116, strong). Ref: H. Choi, et al, EurJOC, 2012, 27, 5141 O

O N

O

N O O

H N

S O

S

O O

O

O

O

Cl

Cl

N

2 Others 2.1 Aminoacids 857 (S)-2,5-Diaminopentanoic acid Type: Protein α-aminoacids. C5H12N2O2 Cryst. (EtOH/Et2O), mp 140 °C, [α]D25 = +11.5°. Source: Green algae Ulva lactuca, Codium decorticatum and Enteromorpha intestinalis, terrestrial plants (free state), terrestrial fungi (component of proteins). Pharm: Treatment of hyperammonaemia and liver disorders. Ref: CRC Press, DNP on DVD, 2012, version 20.2 NH 2 OH

H 2N O

858 α-Allokainic acid α-Allokaininic acid Type: Non-protein α-aminoacids. C10H15NO4 mp 238–242 °C, [α]D20 = +7.7° (c = 1.3, H2O). Source: Red alga Digenea simplex. Pharm: Neurophysiological activity (mammals, potent); anthelminthic; antibacterial. Ref: I. Nitta, et al, Nature (London), 1958, 181, 761│A. Barco, et al, JOC, 1992, 57, 6279│C. Agami, et al, JOC, 1994, 59, 7937 O OH O N H

OH

859 Betonicine Achillein Type: Non-protein α-aminoacids. C7H13NO3 Prisms (EtOH), mp 252 °C (dec), [α]D15 = –36.6° (H2O). Source: Sponge Latrunculia magnifica. Pharm: Antiinflammatory. Ref: Y. Kashman, et al, Tetrahedron, 1985, 41, 1905 OH –

O

N

+

O

https://doi.org/10.1515/9783110655834-002

366

2 Others

860 Carnosadine Type: Non-protein α-aminoacids. C6H12N4O2 Hygroscopic powder. Source: Red alga Grateloupia carnosa. Pharm: Anti-inflammatory. Ref: T. Wakamiya, et al, Tetrahedron, 1984. 40, 235│T. Wakamiya, et al, Tet. Lett., 1984, 25, 4411│D. J. Aitken, et al, Tetrahedron, 1993, 49, 6375 O NH

NH2

HO

N H

NH2

861 5,6-Dibromoabrine Type: Non-protein α-aminoacids. C12H12Br2N2O2 Light brown powder. Source: Sponges Hyrtios sp. and Smenospongia sp. Pharm: PLA2 inhibitor (bee venom PLA2, IC50 = (0.30 ± 0.01)mmol/L); antioxidant (Oxygen Radical Absorbance Capacity (ORAC) = (0.07 ± 0.01), significant). Ref: D. Tasdemir, et al, Zh. Neorg. Khim., 2002, 57, 914│A. Longeon, et al, Mar. Drugs, 2011, 9, 879 O Br

OH

Br

N H

HN

862 N-[[3,4-Dihydro-3S-hydroxy-2S-methyl-2-(4′R-methyl-3′S-pentenyl)2H-1-benzopyran-6-yl]carbonyl]- threonine Type: Non-protein α-aminoacids. C21H29NO6 Source: Marine-derived streptomycete Streptomyces xiamenensis (mangrove sediment, Fujian, China). Pharm: Anti-fibrosis (inhibits proliferation of WI26, blocks adhesion of THP-1 to a monolayer of WI26, and reduces contractile capacity of WI26 cells in three-dimensional free-floating collagen gels; it might indeed have therapeutic potential against fibrosis). Ref: M. -J. Xu, et al, Mar. Drugs, 2012, 10, 639 COOH HO

NH OH

O O

863 (–)-Kainic acid Type: Non-protein α-aminoacids. C10H15NO4 Cryst. +1H2O (EtOH aq), mp 253–254 °C (dec), [α]D24 = –14.8° (c = 1, H2O). Source: Red algae Digenea simplex, Alsidium

2.1 Aminoacids

367

helminthochorton and Centroceras clavulatum. Pharm: Glutamate receptor agonist; neurotoxin; anthelmintic. Ref: S. Murakami, et al, J. Pharm. Soc., Jpn., 1953, 73, 1026│G. A. Kraus, et al, Tet. Lett., 1983, 24, 3427│S. Takano, et al, J. Chem. Soc., Chem. Commun., 1992, 169│J. Cooper, et al, JCS Perkin 1, 1992, 553│S. Yoo, et al, Tet. Lett., 1993, 34. 3435│A. F. Parsons, Tetrahedron, 1996, 52, 4149 O OH O N H

OH

864 4ʹ-Methoxyasperphenamate Type: Non-protein α-aminoacids. C33H32N2O5 Source: Marine-derived fungus Aspergillus elegans from soft coral Sarcophyton sp., (Weizhou coral reef, Giuangxi, China). Pharm: Antibacterial (Staphylococcus epidermidis, modest). Ref: C. -J. Zheng, et al, Mar. Drugs, 2013, 11, 2054 O O O

N H

O

NH O

865 Ovothiol A Type: Non-protein α-aminoacids. C7H11N3O2S Source: Starfish Evasterias troschelii (eggs), cephalopod squid Loligo vulgaris, urchin Paracentrotus lividus, marine polychaete worm Platynereis dumerilii. Pharm: PLA2 inhibitor; oxidoreductase stimulator; redox-active compd; pheromone (to release eggs). Ref: A. Palumbo, et al, Tet. Lett., 1982, 23, 3207│I. Röhl, et al, Z. Naturforsch., Sect. C, 1999, 54, 1145 OH

O H 2N

H SH

N

N

368

2 Others

866 Ovothiol B Type: Non-protein α-aminoacids. C8H13N3O2S Source: Scallop Chlamys hastata. Pharm: PLA2 inhibitor; oxidoreductase stimulator. Ref: E. Turner, et al, Biochemistry, 1987, 26, 4028 O

OH

N H

H SH N

N

867 Ovothiol C Type: Non-protein α-aminoacids. C9H15N3O2S Source: Urchins Strongylocentrotus purpuratus and Paracentrotus lividus. Pharm: Oxidoreductase stimulator. Ref: E. Turner, et al, Biochemistry, 1987, 26, 4028 O

OH

N

H SH N

N

868 Pygmeine Ramalin Type: Non-protein α-aminoacids. C11H15N3O4 Pale yellow powder, mp 144–146 °C (dec), [α]D20 = –2° (c = 1, MeOH). Source: Marine-derived lichen Lichina pygmaea and marine-derived fungus Ramalina terebrata. Pharm: Antioxidant; antibacterial. Ref: C. Roullier, et al, Bioorg. Med. Chem. Lett., 2010, 20, 4582│B. Paudel, et al, Z. Naturforsch., C, 2010, 65, 34

H N

OH

O N H

O OH NH2

869 Echinobetaine A Type: β-Aminoacids. C8H17NO3 [α]D22 = –49° (c = 0.6, MeOH). Source: Sponge Echinodictyum sp. Pharm: Nematocide. Ref: R. J. Capon, et al, JNP, 2005, 68, 179

2.1 Aminoacids

369

–

O

O O

N

+

870 Erinacean Type: β-Aminoacids. C8H9N5O3 Amorph. powder. Source: Sponge Isodictya erinacea (Antarctic). Pharm: Cytotoxic (L5178Y, LD50 = 50 μg/mL); antibacterial (Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli). Ref: B. Moon, et al, JNP, 1998, 61, 116 O HN

OH H N

N

O N H

N

871 3-N-(1Z-Propenyl)-palythine Usujirene Type: Mycosporins. C13H20N2O5 Source: Red alga Palmaria palmata, dinoflagellate Alexandrium excavatum, sponges Dysidea sp. and Prochloron sp. (symbiont). Pharm: Growth factor; UV protectant. Ref: Sekikawa, et al, Jpn. J. Phycol., 1986, 34, 185│J. I. Carreto, et al, J. Plankton Res., 1990, 12, 909 O H N

N Z

O OH

3

HO

OH

872 Aspergillamide A (1998) Type: Miscellaneous modified aminoacids. C28H34N4O3 Amorph. powder, [α]D = –26.2° (c = 3.05, MeOH). Source: Marine-derived fungus Aspergillus sp. (sediment, Saline lake, Bahamas). Pharm: Cytotoxic (HCT116, IC50 = 16 μg/mL). Ref: S. G. Toske, et al, Tetrahedron, 1998, 54, 13459 9Z

N H

Ph HN

O N

O

O NH

370

2 Others

873 Aspergillusol A JBIR-25 Type: Miscellaneous modified aminoacids. C22H24N2O10 Amorph. yellow solid. Source: Marine-derived fungi Aspergillus aculeatus CRI323-04 (Ton Sai Bay, Phi-Phi I., Krabi province, Thailand) and Hyphomycetes sp. CR28109. Pharm: α-Glucosidase inhibitor; antioxidant. Ref: N. Ingavat, et al, JNP, 2009, 72, 2049│K. Motohashi, et al, J. Antibiot., 2009, 62, 703 HO

N

OH

O

OH O

O OH

O

HO

N

OH

874 Dolastatin C Type: Miscellaneous modified aminoacids. C35H57N5O6 Amorph. powder, [α]D25 = –136° (c = 0.066, MeOH). Source: Sea hare Dolabella auricularia. Pharm: Cytotoxic (weak). Ref: H. Sone, et al, Tet. Lett., 1993, 34, 8445│H. Sone, et al, Tet. Lett., 1993, 34, 8449

O

H

O

N O

H

H

N

N O

O

NH2

N H

O

875 Ethyl tumonoate A Type: Miscellaneous modified aminoacids. C21H37NO4 Source: Cyanobacterium Oscillatoria margaritifera. Pharm: Cytotoxic (MTT assay, 10 μg/mL, H460); antiinflammatory (NO assay, RAW264.7, IC50 = 9.8 μmol/L (3.6 μg/mL) with little or no cytotoxicity); Ca2+ oscillations inhibitor (neocortical neurons, 10 μmol/L, nearly complete inhibition). Ref: N. Engene, et al, JNP, 2011, 74, 1737 O OH

O

O

N

876 N-[14-Methyl-3-(13-methyl-4-tetradecenoyloxy)pentadecanoyl]glycine Type: Miscellaneous modified aminoacids. C33H61NO5 Amorph. solid, [α]D25 = –3.4° (c = 0.87, MeOH). Source: Marine bacterium Cytophaga sp. (seawater isolate). Pharm: N-type Ca2+ channel blocker. Ref: T. Morishita, et al, J. Antibiot., 1997, 50, 457

2.1 Aminoacids

371

H N

O

OH

O

O O

877 Purpuroine A Type: Miscellaneous modified aminoacids. C13H16Br3NO3 Source: Sponge Iotrochota purpurea (Sanya, Hainan, China). Pharm: Antimicrobial; kinase inhibitor. Ref: S. Shen, et al, Bioorg. Med. Chem., 2012, 20, 6924 Br

Br

Br N

O O

+

O

–

878 Purpuroine B Type: Miscellaneous modified aminoacids. C13H17Br2NO3 Source: Sponge Iotrochota purpurea (Sanya, Hainan, China). Pharm: Antimicrobial; kinase inhibitor. Ref: S. Shen, et al, Bioorg. Med. Chem., 2012, 20, 6924 Br

Br N

O O

+

O

–

879 Purpuroine C Type: Miscellaneous modified aminoacids. C13H16BrCl2NO3 Source: Sponge Iotrochota purpurea (Sanya, Hainan, China). Pharm: Antimicrobial; kinase inhibitor. Ref: S. Shen, et al, Bioorg. Med. Chem., 2012, 20, 6924 Br

Cl

Cl N

O O

+

O

–

372

2 Others

880 Purpuroine D Type: Miscellaneous modified aminoacids. C13H16Br2INO3 Source: Sponge Iotrochota purpurea (Sanya, Hainan, China). Pharm: Antimicrobial; kinase inhibitor. Ref: S. Shen, et al, Bioorg. Med. Chem., 2012, 20, 6924 Br

Br

I N

O

O

+

–

O

881 Purpuroine E Type: Miscellaneous modified aminoacids. C13H16Br2ClNO3 Source: Sponge Iotrochota purpurea (Sanya, Hainan, China). Pharm: Antimicrobial; kinase inhibitor. Ref: S. Shen, et al, Bioorg. Med. Chem., 2012, 20, 6924 Br

Br

Cl N

O O

+

– O

882 Purpuroine F Type: Miscellaneous modified aminoacids. C15H21I2NO3 Source: Sponge Iotrochota purpurea (Sanya, Hainan, China). Pharm: Antimicrobial; kinase inhibitor. Ref: S. Shen, et al, Bioorg. Med. Chem., 2012, 20, 6924 O I

I

N O

+

–

O

883 Purpuroine G Type: Miscellaneous modified aminoacids. C14H19I2NO3 Source: Sponge Iotrochota purpurea (Sanya, Hainan, China). Pharm: Antimicrobial; kinase inhibitor. Ref: S. Shen, et al, Bioorg. Med. Chem., 2012, 20, 6924

2.1 Aminoacids

373

OH I

I

N

+

–

O

O

884 Purpuroine H Type: Miscellaneous modified aminoacids. C15H21BrINO3 Source: Sponge Iotrochota purpurea (Sanya, Hainan, China). Pharm: Antimicrobial; kinase inhibitor. Ref: S. Shen, et al, Bioorg. Med. Chem., 2012, 20, 6924 O Br

I

N O

+

–

O

885 Purpuroine I Type: Miscellaneous modified aminoacids. C14H19BrINO3 Source: Sponge Iotrochota purpurea (Sanya, Hainan, China). Pharm: Antimicrobial; kinase inhibitor. Ref: S. Shen, et al, Bioorg. Med. Chem., 2012, 20, 6924 OH Br

I

N+

O

O

–

886 Purpuroine J Type: Miscellaneous modified aminoacids. C15H20BrN2O21+ Source: Sponge Iotrochota purpurea (Sanya, Hainan, China). Pharm: Antimicrobial; kinase inhibitor. Ref: S. Shen, et al, Bioorg. Med. Chem., 2012, 20, 6924 N

+

O O Br

N H

374

2 Others

887 Tumonoic acid A N-(3-Hydroxy-2,4-dimethyl-4-dodecenoyl)proline Type: Miscellaneous modified aminoacids. C19H33NO4 Pale yellow oil, [α] = –79° (c = 1.1, CHCl3). Source: Cyanobacteria Lyngbya majuscula and Schizothrix calcicola (assemblage), cyanobacterium Blennothrix cantharidosmum. Pharm: Ca2+ oscillations inhibitor (neocortical neurons, 10 μmol/L, partial inhibition). Ref: G. G. Harrigan, et al, JNP, 1999, 62, 464│B. R. Clark, et al, JNP, 2008, 71, 1530│N. Engene, et al, JNP 2011, 74, 1737 O N

OH OH

O

888 Tumonoic acid F N-(3-Acetoxy-2,4-dimethyldodecanoyl)proline Type: Miscellaneous modified aminoacids. C21H37NO5 Oil, [α] = –173.3° (c = 1.62, MeOH). Source: Cyanobacterium Blennothrix cantharidosmum. Pharm: Ca2+ oscillations inhibitor (neocortical neurons, 10 μmol/L, partial inhibition). Ref: B. R. Clark, et al, JNP, 2008, 71, 1530│N. Engene, et al, JNP, 2011, 74, 1737 O N

OH O O

O

889 Tumonoic acid I Type: Miscellaneous modified aminoacids. C27H47NO7 Oil, [α]D = –40.6° (c = 3, MeOH). Source: Cyanobacterium Blennothrix cantharidosmum. Pharm: Antimalarial (Plasmodium falciparum D6 and W2, IC50 = 2 μmol/L). Ref: B. R. Clark, et al, JNP, 2008, 71, 1530

O

O N

H O O

O O H

OH

2.2 Carbohydrates

375

2.2 Carbohydrates 890 Eodoglucomide A Type: gluco-Hexoses. C30H53NO12 Source: Marine-derived bacterium Bacillus licheniformis (sediment, Ieodo Reef, R. O. Korea). Pharm: Antimicrobial (broad spectrum, moderate). Ref: F. S. Tareq, et al, Org. Lett., 2012, 14, 1464 O O

OH O

HO

O

HO

O O

12

OH

N H

OH O

891 Eodoglucomide B Type: gluco-Hexoses. C29H51NO12 Source: Marine-derived bacterium Bacillus licheniformis (sediment, Ieodo Reef, R. O. Korea). Pharm: Antimicrobial (broad spectrum, moderate); cytotoxic (lung and stomach cancer cells). Ref: F. S. Tareq, et al, Org. Lett., 2012, 14, 1464 O O

OH O

HO

O

HO

O O

OH

12

N H

OH O

892 3-Amino-3-deoxy-D-glucose Type: 3-Amino-3-deoxysugars. C6H13NO5 Source: Marine bacterium Bacillus sp. (deep water). Pharm: Antimicrobial. Ref: N. Fusetani, et al, Experientia, 1987, 43, 464 OH O NH2

OH

OH OH

376

2 Others

893 N-Acetylneuraminic acid Aceneuramic acid; O-Sialic acid Type: 5-Amino-5-deoxysugars. C11H19NO9 mp 185–187 °C (dec). Source: Starfish Asterias rubens, and occurs in eggs, milk, colostrum, submaxillary mucin and meconium, Collocalia mucoid (most abundant source, the nest cementing glycoprotein substance of the Chinese Swiftlet), Pharm: Anti-inflammatory; antiviral; antitussive. Ref: CRC Press, DNP on DVD, 2012, version 20.2 O O NH

OH

O OH OH OH OH

OH

894 Kelletinin I Type: Tetritols. C32H26O12 Sol. MeOH, bases, Et2O; poorly sol. H2O. Source: Prosobranch Kelletia kelletii. Pharm: Antibacterial (Bacillus subtilis); cytotoxic (L1210, 0.4 μg/mL); DNA polymerase inhibitor; reverse transcriptase inhibitor. Ref: A. A. Tymiak, et al, JACS, 1983, 105, 7396 O OH

O O

OH

O O O

OH O

O

OH

895 Kelletinin A Buccinulin Type: Pentitols. C40H32O15 Source: Prosobranch Buccinulum corneum. Pharm: HIV reverse transcriptase (HIV-rt) inhibitor; antibacterial. Ref: G. Cimino, et al, JNP, 1987, 50, 1171

2.2 Carbohydrates

377

OH

OH O O H

O O

O

H

O

H

O

OH O OH

O O

OH

896 Kelletinin II Type: Pentitols. C33H30O12 Source: Prosobranch Kelletia kelletii. Pharm: Antibacterial (Bacillus subtilis); cytotoxic (L1210, 0.4 μg/mL). Ref: A. A. Tymiak, et al, JACS, 1983, 105, 7396 O O

OH O

H

OH

O O

H

O

OH O

O

OH

897 Sarcotride A Type: Cyclitols. C25H50O7 Light yellow oil, [α]D21 = ‒6° (c = 0.15, CH3OH). Source: Sponges Petrosia sp. (Korea waters) and Sarcotragus sp. Pharm: Inhibits SV40 DNA replication in vitro; cytotoxic (hmn solid carcinoma, A549, ED50 > 10 μg/mL, SK-OV-3, ED50 = 9.5 μg/mL, SK-MEL-2, ED50 > 10 μg/mL, XF498, ED50 = 9.8 μg/mL, HCT15, ED50 = 9.4 μg/mL). Ref: D. -K. Kim, et al, JNP, 1999, 62, 773│Y. Liu, et al, Bull. Korean Chem. Soc., 2002, 23, 1467 OH HO O

O OH

HO OH

9

378

2 Others

898 Istamycin A Antibiotic KA 7038I Type: Aminocyclitols. C17H35N5O5 Hemihydrate, mp 78–82 °C, [α]D25 = +120.5° (c = 1, H2O). Source: Marine-derived streptomycete Streptomyces tenjimariensis (psychrophilic, culture filtrate). Pharm: Antibacterial (gram-positive and -negative bacteria, especially aminoglycoside-resistant strains with exception of AAC3-producing organism; Escherichia coli K-12 C600 R135, MIC > 50 μg/mL; Pseudomonas sp., MIC = 50 μg/mL). Ref: D. Ikeda, et al, J. Antibiot., 1979, 32, 964; 1365│T. Deushi, et al, J. Antibiot., 1979, 32, 1061; 1066│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) H N NH2

O

OH NH2

O

N

H 2N

O

O

899 Istamycin B Type: Aminocyclitols. C17H35N5O5 Powder +1/2 H2O (carbonate salt), mp 112–114 °C (carbonate), [α]D25 = +165° (c = 0.4, H2O) (carbonate). Source: Marine-derived streptomycete Streptomyces tenjimariensis (psychrophilic, culture filtrate). Pharm: Antibacterial (gram-positive and -negative bacteria, especially aminoglycosideresistant strains with exception of AAC3-producing organism; Escherichia coli K-12 C600 R135, MIC = 25 μg/mL; Pseudomonas sp., MIC > 25 μg/mL); LD50 (mus, ivn) = 80–160 mg/kg. Ref: D. Ikeda, et al, J. Antibiot., 1979, 32, 964; 1365│M.D. Lebar, et al, NPR, 2007, 24, 774 (rev) H N O

H 2N

OH

NH2 O

N

H2N

O

O

900 Floridoside 2-O-α-D-Galactopyranosylglycerol Type: Disaccharides. C9H18O8 mp 128.5 °C, [α]D = +165° (c = 3.35, H2O). Source: Red algae Mastocarpus stellatus, Plocamium cartilagineum, Laurencia pinnatifida and Iridaea laminaroides. Pharm: Immune system activity (classical complement pathway activator, IC50 (apparent) = 5.9–9.3 μg/mL, MMOA: IgM mediated-effect). Ref: P. M. Abreu, et al, Phytochemistry, 1997, 45, 1601│A. Courtois, et al, Mar. Drugs 2008, 6, 407

2.2 Carbohydrates

379

HO HO

O OH

OH O OH

OH

901 Astebatherioside B Type: Polysaccharides. C34H53NO22 Source: Starfish Asterina bather (Cat Ba I., Haiphong, Vietnam). Pharm: IL-12 p40 production inhibitor (LPS-stimulated bone marrow-derived dendritic cells). Ref: N. P. Thao, et al, Bioorg. Med. Chem. Lett., 2013, 23, 1823 O HO

O

HO O HO

O

O

NH O

O O

OH

OH

O

OH

O

O

OH OH

HO OH

HO

902 Astebatherioside C Type: Polysaccharides. C18H27NO10 Source: Starfish Asterina bather (Cat Ba I., Haiphong, Vietnam). Pharm: IL-12 p40 production inhibitor (LPS-stimulated bone marrow-derived dendritic cells). Ref: N. P. Thao, et al, Bioorg. Med. Chem. Lett., 2013, 23, 1823 O O

O

NH O

HO OH

OH

O

OH OH

903 Astebatherioside D Type: Polysaccharides. C30H46O19 Source: Starfish Asterina bather (Cat Ba I., Haiphong, Vietnam). Pharm: IL-12 p40 protein production inhibitor (LPS-stimulated bone

380

2 Others

marrow-derived dendritic cells). Ref: N. P. Thao, et al, Bioorg. Med. Chem. Lett., 2013, 23, 1823 O HO

HO O

HO

O OH

O

O

O

O O

O OH

OH

OH

O

OH OH

2.3 Nucleosides 904 Adenosine 9-β-D-Ribofuranosyl-9H-purin-6-amin Type: Nucleosides. C10H13N5O4 Cryst. (H2O), mp 234–236 °C, [α]D11 = –61.7° (c = 0.7, H2O). Source: Sponge Dasychalina cyathina, widely distributed in nature, one of the four principal nucleosides of nucleic acid. Pharm: Cardioactive; antiarrhythmic; cardiac depressant; platelet aggregation inhibitor; anxiolytic. Ref: A. J. Weinheimer, et al, Lloydia, 1978, 41, 488 NH2 N

N

N

N

HO

O

OH OH

905 2ʹ-Deoxyadenosine Adenine deoxyriboside Type: Nucleosides. C10H13N5O3 mp 187–192°, [α]D20 = –27° (c = 0.4, H2O). Source: Sponge Dasychalina cyathina. Pharm: Cardioactive, coronary vasodilatory and asystolic agent. Ref: A. J. Weinheimer, et al, Lloydia, 1978, 41, 488 NH2 N

N

N

N HO

O

OH

2.3 Nucleosides

381

906 5ʹ-Deoxy-5-iodotubercidin Type: Nucleosides. C11H13IN4O3 Needles (Py), mp 227–228 °C (dec), [α]D25 = −55° (c = 0.2, MeOH). Source: Red alga Hypnea valendiae. Pharm: Pharmacologically active nucleoside: caused relaxation of muscles and hypothermia in mice and blocked polysynaptic and monosynaptic reflexes. Ref: R. Kazlauskas, et al, Aust. J. Chem., 1983, 36, 165 NH2

I

N N

N

O 1'

H OH

HO

907 Doridosine 1-Methylisoguanosine Type: Nucleosides. C11H15N5O5 Cryst. (H2O), mp 266–267 °C, mp 262–263 °C, [α]D24 = –65.4° (c = 1.0, DMSO), [α]D22 = –54.6° (c = 1.0, H2O). Source: Sponge Tedania digitata (Australia), nudibranch Anisodoris nobilis (California). Pharm: Anti-inflammatory; muscle relaxant; long-acting hypertensive; LD50 (mus, orl) = 1000 mg/kg. Ref: R. J. Quinn, et al, Tet. Lett., 1980, 21, 567│L. P. Davies, Trends Pharmacol. Sci., 1985, 6, 143 NH2 N

N O

N

N

HO O

OH OH

908 Kipukasin H Type: Nucleosides. C18H20N2O9 Source: Marine-derived fungus Aspergillus versicolor ATCC 9577. Pharm: Antibacterial (Staphylococcus epidermidis, MIC = 12.5 μmol/L). Ref: M. Chen, et al, Nat. Prod. Res., 2014, 28, 895 HO

HO O HO O O

O O

N O

N H

382

2 Others

909 Kipukasin I Type: Nucleosides. C18H20N2O9 Source: Marine-derived fungus Aspergillus versicolor ATCC 9577. Pharm: Antibacterial (Staphylococcus epidermidis, MIC = 12.5 μmol/L). Ref: M. Chen, et al, Nat. Prod. Res., 2014, 28, 895

O

HO

HO O O

HO

O O

N O

N H

910 3-Methylcytidine Type: Nucleosides. C10H15N3O5 mp 193–194 °C, (methanesulfonate). Source: Sponge Geodia barretti (psychrophilic, cold water). Pharm: Contractile activity (guinea-pig ileum assay, strong). Ref: G. Lidgren, et al, JNP, 1988, 51, 1277│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) NH

HO

O

N O

OH OH

911 3-Methyl-2ʹ-deoxycytidine Type: Nucleosides. C10H15N3O4 Cryst. (MeOH) (hydrochloride), mp 160 °C (hydrochloride). Source: Sponge Geodia barretti (psychrophilic, cold water). Pharm: Contractile activity (guinea-pig ileum assay, strong). Ref: G. Lidgren, et al, JNP, 1988, 51, 1277│M. D. Lebar, et al, NPR, 2007, 24, 774 (rev) NH N HO

O

N O

OH

2.3 Nucleosides

383

912 Mycalisine A Type: Nucleosides. C13H13N5O3 Oil, [α]D21 = –88° (c = 0.05, EtOH). Source: Sponge Mycale sp. Pharm: Cytotoxic (cell division inhibitor, starfish eggs). Ref: Y. Kato, et al, Tet. Lett., 1985, 26, 3483 N NH2 N N

N O

OH

O

913 Shimofuridin A Type: Nucleosides. C34H44N4O12 Solid (MeOH), mp 210 °C, [α]D19 = –186° (c = 1.4, Py). Source: Ascidian Aplidium multiplicatum (Okinawa). Pharm: Cytotoxic; antifungal; antibacterial (gram-positive bacteria); protein kinase inhibitor. Ref: Y. Doi, et al, Tetrahedron, 1994, 50, 8651 O N

HN

N

N

HO

O

OH O O O

OH

OH

O O

O

914 Spongosine Type: Nucleosides. C11H15N5O5 mp 191–192 °C, [α]D = –43.5° (NaOH aq). Source: An unidentified sponge (order Hadromerida, family Tethyidae). Pharm: Muscle relaxant; CNS depressant; cardioactive; anti-inflammatory; hypothermic. Ref: W. Bergman, et al, JOC, 1956, 21, 226│P. A. Searle, et al, JNP, 1994, 57, 1452

384

2 Others

NH2 N

N O HO

N

N O

OH OH

915 Thymidine-5ʹ-carboxylic acid Type: Nucleosides. C10H12N2O6 Cryst. (H2O), mp 263–265 °C (dec), mp 250–251 °C. Source: Ascidian Aplidium fuscum. Pharm: Thymidine inhibitor; thymidylate kinase inhibitor. Ref: N. Dematte, et al, Comp. Biochem. Physiol., B: Comp. Biochem., 1986, 84, 11 O NH N

O

HO

O

O

OH

916 Toyocamycin Type: Nucleosides. C12H13N5O4 Needles or prisms +1H2O, mp 243 °C, [α]D26 = –55.6° (c = 1, 0.1M HCl). Source: Sponges Jaspis spp., marine-derived streptomycetes Streptomyces sp. (soil sample, Chilkat River in Alaska, 2000), Streptomyces toyocaensis and Streptomyces fungicidicus from sponge Jaspis johnstoni. Pharm: Cytotoxic (P388, GI50 = 0.0023 μg/mL), antibacterial (gram-positive bacteria), LD50 (mus, orl) = 8 mg/kg. Ref: G. R. Pettit, et al, JNP, 2008, 71, 438 NH2

CN

N N

N HO

O

OH OH

917 Trachycladine A Kumusine Type: Nucleosides. C11H14ClN5O3 mp 210–213 °C, [α]D = –19.6° (c = 0.41, MeOH). Source: Sponge Trachycladus laevispirulifer (Western Australia). Pharm:

2.4 S-contaning Compounds

385

Cytotoxic (hmn in vitro: CCRF-CEM, IC50 = 0.4 μg/mL, HCT116, IC50 = 0.9 μg/mL, MCF7, IC50 = 0.2 μg/mL, MDA-MB-435, IC50 = 0.25 μg/mL, MDA-N, IC50 = 0.1 μg/mL); LD50 (brine shrimp) = 0.26 mg/mL. Ref: P. A. Searle, et al, JOC, 1995, 60, 4296│ T. Ichiba, et al, Tet. Lett., 1995, 36, 3977 NH2 N

N Cl

N

N O

OH OH

2.4 S-contaning Compounds 918 6-(2-Aminoethyl)-3,4-dimethoxybenzotrithiane 3,4-Dimethoxy-6-(2ʹ-N,N-dimethylaminoethyl)-5-(methylthio)benzotrithiane Type: Di-, tri-, poly-sulfides. C13H19NO2S4 Pale yellow oil (trifluoroacetate). Source: Ascidian Lissoclinum japonicum (Palau, Oceania). Pharm: Cytotoxic (V79, IC50 = 0.19 μmol/L (0.07 μg/mL), inhibits colony formation) (Wang, 2009); antibacterial (marine bacterium Ruegeria atlantica TUF-D, 50 μg/disk, IZD = 32.4 mm, 20 μg/disk, IZD = 23.3 mm, 5 μg/disk, IZD = 14.2 mm; gram-positive bacterium Staphylococcus aureus, IAM 12544T, 50 μg/disk, IZD = 10.3 mm, gram-negative bacterium Escherichia coli IAM 12119T, 50 μg/disk, IZD = 17.8 mm, 20 μg/disk, IZD = 14.4 mm,); antifungal (Mucor hiemalis IAM 6088, 50 μg/disk, IZD = 23.0 mm, 20 μg/disk, IZD = 17.4 mm, Saccharomyces cerevisiae IAM 1438T, 50 μg/disk, IZD = 11.8 mm, 20 μg/disk, inactive) (Liu, 2005); protein kinase C inhibitor. Ref: R. S. Campagnone, et al, Tetrahedron, 1994, 50, 12785│H. Liu, et al, Tetrahedron, 2005, 61, 8611│ W. Wang, et al, Tetrahedron, 2009, 65, 9598 O O

S

S

S

S

N

919 Antibiotic B 90063 Type: Di-, tri-, poly-sulfides. C28H30N4O6S2 Yellow cryst., mp 73–74 °C, mp 116–118 °C (+2MeOH). Source: Marine bacterium Blastobacter sp. SANK 71894 (Japan waters).

386

2 Others

Pharm: Endothelin converting enzyme inhibitor. Ref: S. Takaishi, et al, J. Antibiot., 1998, 51, 805 O O

O

S

N HN

NH N

S O

O

O

920 Bis(6-bromo-2-tryptaminyl) disulfide Type: Di-, tri-, poly-sulfides. C20H20Br2N4S2 Source: Prosobranch (Marine snail) Calliostoma canaliculatum (defensive mucus). Pharm: Potassium channel agonist; neurotoxin. Ref: W. P. Kelley, et al, J. Biol. Chem., 2003, 278, 34934 NH2

H2 N

S

S

N H

Br

N H

Br

921 Brocazine A Type: Di-, tri-, poly-sulfides. C19H20N2O7S2 Colorless crystals (MeOH), mp 230–232 °C, [α]D25 = −180° (c = 0.05, MeOH). Source: Mangrove-derived fungus Penicillium brocae MA-231 Pharm: Cytotoxic (DU145, IC50 = 4.2 μmol/L, control Paclitaxel, IC50 = 1.5 μmol/L; HeLa, IC50 = 6.8 μmol/L, Paclitaxel, IC50 = 5.0 μmol/L; HepG2, IC50 = 6.4 μmol/L, control Cisplatin, IC50 = 5.1 μmol/L; MCF7, IC50 = 5.5 μmol/L, Paclitaxel, IC50 = 1.8 μmol/L; NCI-H460, IC50 = 4.9 μmol/L, control Cefitinib, IC50 = 7.6 μmol/L; SGC7901, IC50 = 2.6 μmol/L, control Doxorubicin, IC50 = 2.9 μmol/L; SW1990, IC50 = 6.0 μmol/L, control Gemcitabine, IC50 = 2.2 μmol/L; SW480, IC50 = 2.0 μmol/L, Cisplatin, IC50 = 11.3 μmol/L; U251, IC50 = 5.2 μmol/L, Cefitinib, IC50 = 10.8 μmol/L). Ref: L. -H. Meng, et al, JNP, 2014, 77, 1921 O

H O N

O OH

H

H S

S

OH

N

O H O

2.4 S-contaning Compounds

387

922 Brocazine B Type: Di-, tri-, poly-sulfides. C18H18N2O6S2 White powder, [α]D25 = −206° (c = 0.31, MeOH). Source: Mangrove-derived fungus Penicillium brocae MA-231 Pharm: Cytotoxic (DU145, IC50 = 3.6 μmol/L, control Paclitaxel, IC50 = 1.5 μmol/L; HeLa, IC50 = 5.3 μmol/L, Paclitaxel, IC50 = 5.0 μmol/L; HepG2, IC50 = 5.5 μmol/L, control Cisplatin, IC50 = 5.1 μmol/L; MCF7, IC50 = 6.1 μmol/L, Paclitaxel, IC50 = 1.8 μmol/L; NCI-H460, IC50 = 4.0 μmol/L, control Cefitinib, IC50 = 7.6 μmol/L; SGC7901, IC50 = 2.4 μmol/L, control Doxorubicin, IC50 = 2.9 μmol/L; SW1990, IC50 = 6.4 μmol/L, control Gemcitabine, IC50 = 2.2 μmol/L; SW480, IC50 = 1.2 μmol/L, Cisplatin, IC50 = 11.3 μmol/L; U251, IC50 = 3.5 μmol/L, Cefitinib, IC50 = 10.8 μmol/L). Ref: L. -H. Meng, et al, JNP, 2014, 77, 1921 O

H O N

OH

H

H S

S

OH

N

O H

O

923 Brocazine E Type: Di-, tri-, poly-sulfides. C18H20N2O6S2 Colorless crystals (MeOH), mp 240–242 °C, [α]D25 = −208° (c = 0.24, MeOH). Source: Mangrove-derived fungus Penicillium brocae MA-231 Pharm: Cytotoxic (DU145, IC50 = 11.2 μmol/L, control Paclitaxel, IC50 = 1.5 μmol/L; HeLa, IC50 = 4.3 μmol/L, Paclitaxel, IC50 = 5.0 μmol/L; HepG2, IC50 = 5.6 μmol/L, control Cisplatin, IC50 = 5.1 μmol/L; MCF7, IC50 = 9.0 μmol/L, Paclitaxel, IC50 = 1.8 μmol/L; NCI-H460, IC50 = 12.4 μmol/L, control Cefitinib, IC50 = 7.6 μmol/L; SGC7901, IC50 = 3.3 μmol/L, control Doxorubicin, IC50 = 2.9 μmol/L; SW1990, IC50 = 2.1 μmol/L, control Gemcitabine, IC50 = 2.2 μmol/L; U251, IC50 = 6.1 μmol/L, Cefitinib, IC50 = 10.8 μmol/L). Ref: L. -H. Meng, et al, JNP, 2014, 77, 1921 OH

H O N

OH

H

H S

S

OH

N

O H

OH

924 Brocazine F Type: Di-, tri-, poly-sulfides. C18H18N2O6S2 White powder, [α]D25 = −210° (c = 1.35, MeOH). Source: Mangrove-derived fungus Penicillium brocae MA-231 Pharm: Cytotoxic

388

2 Others

(DU145, IC50 = 1.7 μmol/L, control Paclitaxel, IC50 = 1.5 μmol/L; HeLa, IC50 = 6.9 μmol/L, Paclitaxel, IC50 = 5.0 μmol/L; HepG2, IC50 = 2.9 μmol/L, control Cisplatin, IC50 = 5.1 μmol/L; MCF7, IC50 = 3.0 μmol/L, Paclitaxel, IC50 = 1.8 μmol/L; NCI-H460, IC50 = 8.9 μmol/L, control Cefitinib, IC50 = 7.6 μmol/L; SGC7901, IC50 = 8.0 μmol/L, control Doxorubicin, IC50 = 2.9 μmol/L; SW1990, IC50 = 5.9 μmol/L, control Gemcitabine, IC50 = 2.2 μmol/L; U251, IC50 = 5.3 μmol/L, Cefitinib, IC50 = 10.8 μmol/L). Ref: L. -H. Meng, et al, JNP, 2014, 77, 1921 O

H O N

OH

H

H S

S

OH

N

O H

OH

925 (R,R)-16,17-Dehydrodiscorhabdin W Type: Di-, tri-, poly-sulfides. C36H20Br2N6O4S2 [α]D = +80° (c = 0.02, MeOH). Source: Sponge Latrunculia wellingtonensis [Syn. Biannulata wellingtonesis] (Wellington, New Zealand). Pharm: Cytotoxic. Ref: T. Grkovic, et al, Tetrahedron, 2009, 65, 6335 O

O

H N

H N

H N

S

H N

S N

N

16 17

O

Br

Br

O

926 (S,S)-16,17-Dehydrodiscorhabdin W Type: Di-, tri-, poly-sulfides. C36H20Br2N6O4S2 [α]D = –120° (c = 0.02, MeOH). Source: Sponge Latrunculia wellingtonensis [Syn. Biannulata wellingtonesis] (Wellington, New Zealand). Pharm: Cytotoxic. Ref: T. Grkovic, et al, Tetrahedron, 2009, 65, 6335 O

O

H N

H N

H N

S

H N

S N

N

16 17

Br

O

O

Br

2.4 S-contaning Compounds

389

927 6-Deoxy-5a,6-didehydrogliotoxin Type: Di-, tri-, poly-sulfides. C13H12N2O3S2 White solid, [α]D25 = −4.6° (c = 0.03, MeOH). Source: Deep-sea fungus Penicillium sp. strain JMF034 (sediments of Suruga Bay, Japan). Pharm: Cytotoxic (P388, IC50 = 0.058 μmol/L); inhibitor of histone methyltransferase (HMT) G9A (IC50 = 55 μmol/L). Ref: Y. Sun, et al, JNP, 2011, 75, 111

O N

S

S

N

O OH

928 11-Deoxyverticillin A Type: Di-, tri-, poly-sulfides. C30H28N6O5S4 Yellow cryst. (CH2Cl2/MeOH). Source: Marine-derived fungus Penicillium sp. CNC-350 from green alga Avrainvillea longicaulis (Caribbean Sea). Pharm: Cytotoxic (HCT116, IC50 = 30 ng/mL). Ref: B. W. Son, et al, Nat. Prod. Lett., 1999, 13, 213

O S H H S N N

N O OH

N N S H H S N O

O

929 5a,6-Didehydrogliotoxin Type: Di-, tri-, poly-sulfides. C13H12N2O4S2 Source: Deep-sea fungus Penicillium sp. strain JMF034 (sediments of Suruga Bay, Japan). Pharm: Cytotoxic (P388, IC50 = 0.056 μmol/L); inhibitor of histone methyltransferase (HMT) G9A (IC50 = 2.6 μmol/L). Ref: Y. Sun, et al, JNP, 2011, 75, 111

O N HO

S

S

N

O OH

390

2 Others

930 11,11ʹ-Dideoxyverticillin A Type: Di-, tri-, poly-sulfides. C30H28N6O4S4 Solid, [α]D = +624.1°. Source: Marinederived fungus Penicillium sp. CNC-350 from green alga Avrainvillea longicaulis (Caribbean Sea). Pharm: Cytotoxic (HCT116, IC50 = 30 ng/mL). Ref: B. W. Son, et al, Nat. Prod. Lett., 1999, 13, 213

O S H H S N N

N

N N S H H S N O

O

O

931 N,N-Dimethyl-5-(methylthio)varacin 6-Amino-8,9-dimethoxy-N,N-dimethyl-7-(methylthio)benzopentathiepin Type: Di-, tri-, poly-sulfides. C13H19NO2S6 Pale yellow oil (trifluoroacetate). Source: Ascidian Lissoclinum japonicum. Pharm: Cytotoxic (V79, IC50 = 0.15 μmol/L (006 μg/mL), inhibits colony formation) (Wang, 2009); antibacterial (marine bacterium Ruegeria atlantica TUF-D, 50 μg/disk, IZD = 30.0 mm, 20 μg/disk, IZD = 24.5 mm, 5 μg/disk, IZD = 15.8 mm; gram-positive bacterium Staphylococcus aureus, IAM 12544T, 50 μg/disk, IZD = 14.2 mm, gram-negative bacterium Escherichia coli IAM 12119T, 50 μg/disk, IZD = 17.1 mm, 20 μg/disk, IZD = 13.1 mm); antifungal (Mucor hiemalis IAM 6088, 50 μg/disk, IZD = 26.2 mm, 20 μg/disk, IZD = 19.6 mm, Saccharomyces cerevisiae IAM 1438T, 50 μg/disk, IZD = 15.2 mm,, 20 μg/disk, IZD = 10.5 mm) (Liu, 2005). Ref: R. S. Campagnone, et al, Tetrahedron, 1994, 50, 12785│H. Liu, et al, Tetrahedron, 2005, 61, 8611│W. Wang, et al, Tetrahedron, 2009, 65, 9598 O O

S

S

S

S

S S

N

932 Gliotoxin Type: Di-, tri-, poly-sulfides. C13H14N2O4S2 Monoclinic cryst. (MeOH), mp 221 °C (dec), [α]D25 = –290° (c = 0.078, EtOH). Source: Marine-derived fungus Pseudallescheria sp.

2.4 S-contaning Compounds

391

from brown alga Agarum cribrosum (Korea waters), and occurs in both terrestrial and marine fungi. Pharm: Antibacterial (MRSA and MDRSA); antiviral; immunomodulating activity; LD50 (mus, orl) = 67 mg/kg, hepatotoxic. Ref: K. Yoshida, et al, Prog. Biochem. Pharmacol., 1988, 22, 66│X. F. Li, et al, J. Antibiot., 2006, 59, 248 O S N

N S H OH

OH

O

933 Gliotoxin Type: Di-, tri-, poly-sulfides. C13H14N2O4S2 [α]D25 = −440° (c = 0.11, MeOH). Source: Deep-sea fungus Penicillium sp. strain JMF034 (sediments of Suruga Bay, Japan). Pharm: Cytotoxic (P388, IC50 = 0.024 μmol/L); inhibitor of histone methyltransferase (HMT) G9A (IC50 = 6.4 μmol/L). Ref: Y. Sun, et al, JNP, 2011, 75, 111

O HO

H

N

S

S

N

O OH

934 Gliotoxin G Type: Di-, tri-, poly-sulfides. C13H14N2O4S4 Source: Deep-sea fungus Penicillium sp. strain JMF034 (sediments of Suruga Bay, Japan). Pharm: Cytotoxic (P388, IC50 = 0.020 μmol/L); inhibitor of histone methyltransferase (HMT) G9A (IC50 = 2.1 μmol/L). Ref: Y. Sun, et al, JNP, 2011, 75, 111

S

S O

HO

H

N

S N

O

S

OH

935 (+)-5-Hydroxy-4-(4-hydroxy-3-methoxyphenyl)-4-(2-imidazolyl)-1,2,3-trithiane Type: Di-, tri-, poly-sulfides. C13H14N2O3S3 Yellow gum, [α]D20 = +26° (c = 0.1, MeOH). Source: Ascidian Aplidium sp. (New Zealand). Pharm: Cytotoxic (P388, IC50 = 13 μg/mL). Ref: B. R. Copp, et al, Tet. Lett., 1989, 30, 3703

392

2 Others

OH HN N S

S

S OH O

936 (–)-5-Hydroxy-4-(4-hydroxy-3-methoxyphenyl)-4-(2-imidazolyl)1,2,3-trithiane Type: Di-, tri-, poly-sulfides. C13H14N2O3S3 [α]D20 = –26° (c = 0.1, MeOH). Source: Ascidian Hypsistozoa fasmeriana (New Zealand). Pharm: Cytotoxic (P388, IC50 = 21.6 μmol/L); antibacterial (Bacillus subtilis, 120 μg/disk, IZD = 4 mm); antifungal (Candida albicans, 120 μg/disk, IZD = 4 mm). Ref: A. N. Pearce, et al, JOC, 2001, 66, 8257 OH HN N S

S

S OH O

937 Lenthionine 1,2,3,5,6-Pentathiacycloheptane Type: Di-, tri-, poly-sulfides. C2H4S5 Crystal (CH2Cl2), mp 60–61 °C. Source: Red alga Chondria californica, mushroom Lentinus edodes. Pharm: Antibacterial (gram-positive and -negative bacteria); antifungal (Candida albicans); odour. Ref: K. Morita, et al, CPB, 1967, 15, 998│S. J. Wratten, et al, JOC, 1976, 41, 2465

S

S S

S

S

938 Leptosin A Type: Di-, tri-, poly-sulfides. C32H32N6O7S6 Pale yellow powder, mp 216–218 °C, [α]D = +237° (c = 0.49, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (in vitro, P388, ED50 = 1.85 × 10–3 μg/mL; control Mitomycin, ED50 = 4.40 × 10–2 μg/mL); antineoplastic (in vivo, ICR mouse S180, dose of 0.5 mg/kg, T/C = 260%). Ref: C. Takahashi, et al, JCS Perkin 1, 1994, 1859

2.4 S-contaning Compounds

393

OH O H H N N

S

S

S

S

N O

6

OH OH 6'

N N S H H

O S

N

O

939 Leptosin B Type: Di-, tri-, poly-sulfides. C32H32N6O7S5 Pale yellow powder, mp 210–213 °C, [α]D = +392° (c = 0.50, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (in vitro, P388, ED50 = 2.40 × 10–3 μg/mL; control Mitomycin, ED50 = 4.40 × 10–2 μg/mL). Ref: C. Takahashi, et al, JCS Perkin 1, 1994, 1859 OH O H H N N

S S

S

N O

6

OH OH 6'

N N S H H O

O S

N

940 Leptosin C Type: Di-, tri-, poly-sulfides. C32H32N6O7S4 Pale yellow powder, mp 208–210 °C, [α]D = +237° (c = 0.36, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (in vitro, P388, ED50 = 1.75 × 10–3 μg/mL; control Mitomycin, ED50 = 4.40 × 10–2 μg/mL); antineoplastic (in vivo, ICR mouse S180, dose of 0.25 mg/kg, T/C = 293%). Ref: C. Takahashi, et al, JCS Perkin 1, 1994, 1859

394

2 Others

OH O S H H N N

S

N O

6

OH OH 6'

N N S H H O

O S

N

941 Leptosin D Type: Di-, tri-, poly-sulfides. C25H24N4O3S2 Pale yellow powder, mp 190–192 °C, [α]D = +436° (c = 0.51, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. from brown alga Sargassum tortile. Pharm: Cytotoxic (in vitro, P388, ED50 = 8.60 × 10–2 μg/mL; control Mitomycin, ED50 = 4.40 × 10–2 μg/mL). Ref: C. Takahashi, et al, JCS Perkin 1, 1994, 1859 H N

OH O N H H O

N

S S

N

942 Leptosin E Type: Di-, tri-, poly-sulfides. C25H24N4O3S3 Pale yellow powder, mp 229–231 °C, [α]D = +563° (c = 0.32, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. from brown alga Sargassum tortile. Pharm: Cytotoxic (in vitro, P388, ED50 = 4.60 × 10–2 μg/mL; control Mitomycin, ED50 = 4.40 × 10–2 μg/mL). Ref: C. Takahashi, et al, JCS Perkin 1, 1994, 1859

2.4 S-contaning Compounds

395

H N

OH

N N S H H

O S S

O

N

943 Leptosin F Type: Di-, tri-, poly-sulfides. C25H24N4O3S4 Pale yellow powder, mp 219–221 °C, [α]D = +452° (c = 0.39, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. from brown alga Sargassum tortile. Pharm: Cytotoxic (in vitro, P388, ED50 = 5.60 × 10–2 μg/mL; control Mitomycin, ED50 = 4.40 × 10–2 μg/mL). Ref: C. Takahashi, et al, JCS Perkin 1, 1994, 1859 H N

OH

N NS S H H S S

O

O N

944 Leptosin G Type: Di-, tri-, poly-sulfides. C32H32N6O7S7 Pale yellow powder, mp 205–210 °C, [α]D24 = +481° (CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 4.6 × 10−3 μg/mL). Ref: C. Takahashi, et al, Phytochemistry, 1995, 38, 155│C. Takahashi, et al, Tetrahedron, 1995, 51, 3483 HO S O H H N N

N N H H O

S

N O S S OH OH S O S N S

396

2 Others

945 Leptosin G1 Type: Di-, tri-, poly-sulfides. C32H32N6O7S6 Powder, mp 210–212 °C, [α]D24 = +558° (CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 4.3 × 10−3 μg/mL). Ref: C. Takahashi, et al, Phytochemistry, 1995, 38, 155│C. Takahashi, et al, Tetrahedron, 1995, 51, 3483 HO

S

O

N

H H N N

S O S

OH OH

S O

N N H H

S N

O

S

946 Leptosin G2 Type: Di-, tri-, poly-sulfides. C32H32N6O7S5 Pale yellow powder, mp 210–215 °C, [α]D24 = +303° (CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 4.4 × 10−3 μg/mL). Ref: C. Takahashi, et al, Phytochemistry, 1995, 38, 155│C. Takahashi, et al, Tetrahedron, 1995, 51, 3483 HO O S S H H N N

N O

OH OH S N N H H O

O S N S

947 Leptosin H Type: Di-, tri-, poly-sulfides. C32H32N6O7S6 Pale yellow powder, mp 214–215 °C, [α]D24 = +298° (CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 3.0 × 10−3 μg/mL). Ref: C. Takahashi, et al, Phytochemistry, 1995, 38, 155│C. Takahashi, et al, Tetrahedron, 1995, 51, 3483

2.4 S-contaning Compounds

397

HO O S H H S N N

N O OH OH S O S

N N H H

N

O

S S

948 Leptosin I Type: Di-, tri-, poly-sulfides. C32H32N6O7S4 Pale yellow powder, mp 218–220 °C, [α]D24 = +212° (c = 0.13, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 1.13 μg/mL). Ref: C. Takahashi, et al, J. Antibiot., 1994, 47, 1242 OH O

3'

H H N N

HO

N N H H O

N O O S O S N

S S

949 Leptosin J Type: Di-, tri-, poly-sulfides. C32H32N6O7S4 Pale yellow powder, mp 215–216 °C, [α]D24 = +188° (c = 0.21, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 1.25 μg/mL). Ref: C. Takahashi, et al, J. Antibiot., 1994, 47, 1242

398

2 Others

OH O

3'

H H N N

N O O

HO

S O S

N N H H

N

O

S S

950 Leptosin K Type: Di-, tri-, poly-sulfides. C34H36N6O6S4 Prisms (EtOAc), mp 222–224 °C, [α]D25 = +76.7° (CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 3.8 × 10−3 μg/mL). Ref: C. Takahashi, et al, Phytochemistry, 1995, 38, 155│C. Takahashi, et al, Tetrahedron, 1995, 51, 3483

O H H N

S N

N S O OH OH

N N H H O

O S

S N

951 Leptosin K1 Type: Di-, tri-, poly-sulfides. C34H36N6O6S5 Pale yellow powder, mp 209–212 °C, [α]D25 = +88.9° (CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 2.2 × 10−3 μg/mL). Ref: C. Takahashi, et al, Phytochemistry, 1995, 38, 155│C. Takahashi, et al, Tetrahedron, 1995, 51, 3483

2.4 S-contaning Compounds

O S H H S N N

399

N O

OH OH S O

N N H H

S N

O

S

952 Leptosin K2 Type: Di-, tri-, poly-sulfides. C34H36N6O6S6 Pale yellow powder, mp 214–216 °C, [α]D25 = +482.8° (CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 2.1 × 10−3 μg/mL). Ref: C. Takahashi, et al, Phytochemistry, 1995, 38, 155│C. Takahashi, et al, Tetrahedron, 1995, 51, 3483

O H H N N

S

S

N O OH OH S

N N H H O

O N

S

S S

953 Leptosin M Type: Di-, tri-, poly-sulfides. C33H36N6O8S4 Pale yellow powder, mp 223–226 °C, [α]D = +478° (c = 0.1, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 1.05 μg/mL, control 5-FU, ED50 = 0.058 μg/mL); cytotoxic (panel of 39 hmn cancer cell lines, MG-MID Log10 GI50 (mol/L) = −5.25, Delta = 0.54, Range = 1.18); topoisomerase II inhibitor (IC50 = 59.1 μmol/L); kinases inhibitor (PTK and CaMKIII, 10 μg/mL, InRt = 30%–70%); topoisomerase II inhibitor (IC50 = 59.1 μmol/L). Ref: T. Yamada, et al, Tetrahedron, 2002, 58, 479

400

2 Others

OH O

N

H H N N 11'

HO

O

O OH

S

11

N N H H

O S N

O

S S

954 Leptosin M1 Type: Di-, tri-, poly-sulfides. C33H36N6O8S2 Pale yellow powder, mp 219–222 °C, [α]D = +140° (c = 0.18, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 1.4 μg/mL, control 5-FU, ED50 = 0.058 μg/mL). Ref: T. Yamada, et al, Tetrahedron, 2002, 58, 479 OH O

N

H H N N 11'

O

HO

OH

11

N N S S H H O

O

O N

955 Leptosin N Type: Di-, tri-, poly-sulfides. C33H36N6O8S4 Pale yellow powder, mp 226–228 °C, [α]D = +276° (c = 0.16, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 0.18 μg/mL, control 5-FU, ED50 = 0.058 μg/mL). Ref: T. Yamada, et al, Tetrahedron, 2002, 58, 479

2.4 S-contaning Compounds

401

OH O

N

H H N N 11'

HO

O

OH S

11

N N H H

O

O S N

O

S S

956 Leptosin N1 Type: Di-, tri-, poly-sulfides. C33H36N6O8S3 Pale yellow powder, mp 227–229 °C, [α]D = +347° (c = 0.14, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-4 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, ED50 = 0.19 μg/mL, control 5-FU, ED50 = 0.058 μg/mL). Ref: T. Yamada, et al, Tetrahedron, 2002, 58, 479 OH O

N

H H N N 11'

HO

O

O

OH

11

NS N H H S S N O

O

957 Leptosin O Type: Di-, tri-, poly-sulfides. C33H36N6O7S2 Pale yellow powder, mp 220–222 °C, [α]D24 = –99° (c = 0.08, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-N80 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, significant). Ref: T. Yamada, et al, Heterocycles, 2004, 63, 641

402

2 Others

OH

H N

O H

N N

O

OH OH

N H

H

O

N 3

N

O

S

S

958 Leptosin P Type: Di-, tri-, poly-sulfides. C33H36N6O7S2 Pale yellow powder, mp 233–235 °C, [α]D24 = +35° (c = 0.17, CHCl3). Source: Marine-derived fungus Leptosphaeria sp. OUPS-N80 from brown alga Sargassum tortile. Pharm: Cytotoxic (P388, significant). Ref: T. Yamada, et al, Heterocycles, 2004, 63, 641 OH

H N

O H

N N OH

O

OH

N H

H O

O

N 3

N S

S

959 Lissoclibadin 1 Type: Di-, tri-, poly-sulfides. C39H57N3O6S7 [α]D = –3.6° (c = 0.1, CHCl3) (tris(TFA) salt). Source: Ascidian Lissoclinum cf. badium. Pharm: Cytotoxic (V79, IC50 = 0.21 μmol/L (0.19 μg/mL), previous data 0.20 μmol/L (0.18 μg/mL), 0.40 μmol/L (0.35 μg/mL), inhibits colony formation; L1210, IC50 = 1.50 μmol/L (1.33 μg/mL), cell proliferation inhibitor) (Wang, 2009); antibacterial (marine bacterium Ruegeria atlantica TUF-D, 50 μg/disk, IZD = 23.4 mm, 20 μg/disk, IZD = 15.2 mm, 5 μg/disk, inactive; grampositive bacterium Staphylococcus aureus, IAM 12544T, 50 μg/disk, inactive, gram-negative bacterium Escherichia coli IAM 12119T, 50 μg/disk, inactive; antifungal (Mucor hiemalis IAM6088, 50 μg/disk, inactive, Saccharomyces

2.4 S-contaning Compounds

403

cerevisiae IAM 1438T, 50 μg/disk, inactive)) (Liu, 2005). Ref: H. Liu, et al, Tetrahedron, 2005, 61, 8611│W. Wang, et al, Tetrahedron, 2009, 65, 9598 N

N

S

S S

S O

O S

O

S

O

O N O

S

960 Lissoclibadin 2 Type: Di-, tri-, poly-sulfides. C26H38N2O4S5 Source: Ascidian Lissoclinum cf. badium. Pharm: Cytotoxic (V79, IC50 = 0.08 μmol/L (0.05 μg/mL), inhibits colony formation; L1210, IC50 = 2.04 μmol/L (1.23 μg/mL), cell proliferation inhibitor) (Wang, 2009); antibacterial (marine bacterium Ruegeria atlantica TUF-D, 50 μg/disk, IZD = 28.2 mm, 20 μg/disk, IZD = 21.2 mm, 5 μg/disk, IZD = 12.2 mm, gram-positive bacterium Staphylococcus aureus, IAM 12544T, 50 μg/disk, inactive, gram-negative bacterium Escherichia coli IAM 12119T, 50 μg/disk, inactive); antifungal (Mucor hiemalis IAM 6088, 50 μg/disk, IZD = 13.8 mm, 20 μg/disk, inactive, Saccharomyces cerevisiae IAM 1438T, 50 μg/disk, inactive) (Liu, 2005). Ref: H. Liu, et al, Tetrahedron, 2005, 61, 8611│W. Wang, et al, Tetrahedron, 2009, 65, 9598

N O 3

S

S S

O S S

5

6'

O

O N

961 Lissoclibadin 4 Type: Di-, tri-, poly-sulfides. C22H30N2O4S3 Source: Ascidian Lissoclinum cf. badium. Pharm: Cytotoxic (V79, IC50 = 0.71 μmol/L (0.34 μg/mL), inhibits colony formation; L1210, IC50 = 1.94 μmol/L (0.94 μg/mL), cell proliferation inhibitor). Ref: T. Nakazawa, et al, JNP, 2007, 70, 439│W. Wang, et al, Tetrahedron, 2009, 65, 9598

404

2 Others

N HO 3

S

S

O S

5

6'

O

HO N

962 Lissoclibadin 5 Type: Di-, tri-, poly-sulfides. C24H34N2O4S4 Source: Ascidian Lissoclinum cf. badium. Pharm: Cytotoxic (V79, IC50 = 0.058 μmol/L (0.031 μg/mL), inhibits colony formation; L1210, IC50 = 0.97 μmol/L (0.53 μg/mL); cell proliferation inhibitor). Ref: T. Nakazawa, et al, JNP, 2007, 70, 439

N HO 3

S

S S

O S

5

6'

O

O N

963 Lissoclibadin 6 Type: Di-, tri-, poly-sulfides. C24H34N2O4S3 Source: Ascidian Lissoclinum cf. badium. Pharm: Cytotoxic (V79, IC50 = 0.058 μmol/L (0.029 μg/mL), inhibits colony formation; L1210, IC50 = 0.63 μmol/L (0.32 μg/mL); cell proliferation inhibitor). Ref: T. Nakazawa, et al, JNP, 2007, 70, 439 N OH S

S

O

S

O O

N

2.4 S-contaning Compounds

405

964 Lissoclibadin 7 Type: Di-, tri-, poly-sulfides. C22H30N2O4S4 Source: Ascidian Lissoclinum cf. badium. Pharm: Cytotoxic (V79, IC50 = 0.17 μmol/L (0.09 μg/mL), inhibits colony formation; L1210, IC50 = 2.17 μmol/L (1.12 μg/mL), cell proliferation inhibitor). Ref: T. Nakazawa, et al, JNP, 2007, 70, 439│W. Wang, et al, Tetrahedron, 2009, 65, 9598 N

OH O

S

S

S

S

O OH

N

965 Lissoclibadin 8 Type: Di-, tri-, poly-sulfides. C52H76N4O8S12 Yellow film (tetrakis(trifluoroacetate) salt). Source: Ascidian Lissoclinum cf. badium (Manado, Indonesia). Pharm: Cytotoxic (V79, IC50 = 0.14 μmol/L (0.18 μg/mL), inhibits colony formation; L1210, IC50 = 2.00 μmol/L (2.54 μg/mL), cell proliferation inhibitor). Ref: W. Wang, et al, Tetrahedron, 2009, 65, 9598 O

O O

S

S

O

S S

N

N

S

S

S

S

N

N

S S S

O O

S

O O

966 Lissoclibadin 9 Type: Di-, tri-, poly-sulfides. C35H49N3O6S6 Yellow film (tetrakis (trifluoroacetate) salt). Source: Ascidian Lissoclinum cf. badium (Manado, Indonesia). Pharm: Cytotoxic (V79, IC50 = 0.63 μmol/L (0.50 μg/mL), inhibits colony formation; L1210, IC50 = 0.38 μmol/L (0.30 μg/mL), cell proliferation inhibitor). Ref: W. Wang, et al, Tetrahedron, 2009, 65, 9598

406

2 Others

N O

O

HO

HO

N

S S

S

S

S O

N O

S

967 Lissoclibadin 13 Type: Di-, tri-, poly-sulfides. C13H19NO2S3 Yellow film (bistrifluoroacetate salt), [α]D = –6.1° (c = 0.2, MeOH). Source: Ascidian Lissoclinum cf. badium (Manado, Indonesia). Pharm: Cytotoxic (V79, IC50 = 0.44 μmol/L (0.14 μg/mL), inhibits colony formation; L1210, IC50 = 2.20 μmol/L (0.70 μg/mL), cell proliferation inhibitor). Ref: W. Wang, et al, Tetrahedron, 2009, 65, 9598 N S O

S

S

OH

968 Lissoclibadin14 Isolissoclinotoxin B; 9-[2-(Dimethylamino)ethyl]-7-methoxy-6-benzopentathiepinol Type: Di-, tri-, poly-sulfides. C11H15NO2S5 Yellow film (bistrifluoroacetate salt). Source: Ascidians Lissoclinum cf. badium (Manado, Indonesia) and Lissoclinum cf. badium (Papua New Guinea). Pharm: Cytotoxic (V79, IC50 = 0.70 μmol/L (0.25 μg/mL), inhibits colony formation; L1210, IC50 = 1.80 μmol/L (0.64 μg/mL), cell proliferation inhibitor). Ref: J. A. Clement, et al, Bioorg. Med. Chem., 2008, 16, 10022│W. Wang, et al, Tetrahedron, 2009, 65, 9598 N S S S S S

O OH

969 lissoclinotoxin A 9-(2-Aminoethyl)-6-methoxy-7-benzopentathiepinol Type: Di-, tri-, poly-sulfides. C9H11NO2S5 Amorph. yellow solid, mp 245–250 °C. Source: Ascidian Lissoclinum perforatum. Pharm: Antimicrobial; antifungal. Ref: M. Litaudon, et al, Tet. Lett., 1991, 32, 911,│M. Litaudon, et al, Tetrahedron, 1994, 50, 5323

2.4 S-contaning Compounds

407

O S S

HO

S S S H 2N

970 lissoclinotoxin B 8,9,10,11-Tetrahydro-6-methoxy-1,2,3,4,5-pentathiepino[6,7-f]isoquinolin-7-ol Type: Di-, tri-, poly-sulfides. C10H11NO2S5 Pale yellow powder, mp 310–313 °C. Source: Ascidian Lissoclinum perforatum. Pharm: Antimicrobial; antiplasmodial. Ref: M. Litaudon, et al, Tet. Lett., 1991, 32, 911,│M. Litaudon, et al, Tetrahedron, 1994, 50, 5323 O S S

HO

S S S HN

971 Lissoclinotoxin D 4,10-Bis(2-aminoethyl)-1,7-dimethoxydibenzo[c,g][1,2,5,6]-tetrathiocin-2,8-diol Type: Di-, tri-, poly-sulfides. C18H22N2O4S4 Colorless amorph. solid. Source: Ascidian Lissoclinum sp. (Great Barrier Reef). Pharm: Antifungal (Candida albicans). Ref: P. A. Searle, et al, JOC, 1994, 59, 6600 NH2 O HO

S

S

S

S

OH O

NH2

972 Lissoclinotoxin F Type: Di-, tri-, poly-sulfides. C26H38N2O4S5 Light brown film (bis-TFA salt). Source: An unidentified ascidian (Philippines). Pharm: Cytotoxic (PTEN-deficient MDA-MB -468, IC50 = 1.5 μg/mL, note: PTEN is a identified tumor suppressor gene located on hmn chromosome 10q23.3); cytotoxic (V79, IC50 = 0.28 μmol/L (0.17 μg/mL), colony formation inhibitor) (Wang, 2009); antibacterial (marine bacterium Ruegeria atlantica TUF-D, 50 μg/disk, IZD = 20.0 mm, 20 μg/disk, IZD = 12.1 mm, 5 μg/disk, inactive; gram-positive bacterium Staphylococcus aureus, IAM 12544T, 50 μg/disk,

408

2 Others

inactive, gram-negative bacterium Escherichia coli IAM 12119T, 50 μg/disk, inactive); antifungal (Mucor hiemalis IAM 6088, 50 μg/disk, IZD = 18.0 mm, 20 μg/disk, IZD = 10.5 mm, Saccharomyces cerevisiae IAM 1438T, 50 μg/disk, inactive) (Liu, 2005). Ref: R. A. Davis, et al, Tetrahedron, 2003, 59, 2855│H. Liu, et al, Tetrahedron, 2005, 61, 8611│W. Wang, et al, Tetrahedron, 2009, 65, 9598

O

S

O

S

O

O S

S

S

N

N

973 Luteoalbusin A Type: Di-, tri-, poly-sulfides. C23H20N4O3S2 Source: Deep-sea fungus Acrostalagmus luteoalbus SCSIO F457 (sediment, South China Sea). Pharm: Cytotoxic (SF268, MCF7, NCI-H460 and HepG2, IC50 = 0.23–1.31 μmol/L). Ref: F. -Z. Wang, et al, Bioorg. Med. Chem. Lett., 2012, 22, 7265 H N

O S N

N S N H

H

O

OH

974 Luteoalbusin B Type: Di-, tri-, poly-sulfides. C23H20N4O3S3 Source: Deep-sea fungus Acrostalagmus luteoalbus SCSIO F457 (sediment, South China Sea). Pharm: Cytotoxic (SF268, MCF7, NCI-H460 and HepG2, IC50 = 0.23–1.31 μmol/L). Ref: F. -Z. Wang, et al, Bioorg. Med. Chem. Lett., 2012, 22, 7265 H N

O S N S

N S N H

H

O

OH

975 5-(Methylthio)varacin A Type: Di-, tri-, poly-sulfides. C11H15NO2S4 5-(Methylthio)varacin and 5-(Methylthio) varacin A is an inseparable mixture Source: Ascidian Lissoclinum sp. (Pohnpei I.,

2.4 S-contaning Compounds

409

Federated States of Micronesia). Pharm: PKC inhibitor. Ref: R. S. Compagnone, et al, Tetrahedron, 1994, 50, 12785 O O

S

S

S

S

NH2

976 Namenamicin Type: Di-, tri-, poly-sulfides. C43H62N2O14S5 Source: Ascidians Didemnum proliferum and Polysyncraton lithostrotum. Pharm: Cytotoxic (3Y1, IC50 = 13 pg/mL, control Adriamycin, IC50 = 13000 pg/mL; HeLa, IC50 = 34 pg/mL, Adriamycin, IC50 = 17000 pg/mL; P388, IC50 = 3.3 pg/mL, Adriamycin, IC50 = 52000 pg/mL); antibacterial. Ref: L. A. McDonald, et al, JACS, 1996, 118, 10898│N. Oku, et al, JACS, 2003, 125, 2044│U. Galm, et al, Chem. Rev., 2005, 105, 739 O

O

O NH HO S

S

S

O

S 4'

O OH

OO O HO

S OH

O

4''

NH O

977 Nereistoxin Type: Di-, tri-, poly-sulfides. C5H11NS2 Source: Annelid Polychaete worm Lumbriconereis heteropoda. Pharm: Insecticide. Ref: T. Okaichi, et al, Arg. Biol. Chem., 1962, 26, 224

S S

N

410

2 Others

978 Pentaporin A Type: Di-, tri-, poly-sulfides. C42H62O12S4 [α]D25 = –13.1° (c = 0.006, MeOH) (di-Na salt). Source: Bryozoan Pentapora fascialis. Pharm: Anthelmintic. Ref: S. Eisenbarth, et al, Tetrahedron, 2002, 58, 8461 OH 1'

HO

O

S

S

HO

O

O

S

O

O S OH O

OH

1''

OH

979 Polycarpamine A 3,4-Dihydro-1,6,7-trimethoxy-N,N-dimethyl-8-(methyldithio)-1H-2-benzothiopyran-5amine Type: Di-, tri-, poly-sulfides. C15H23NO3S3 Yellow oil. Source: Ascidian Polycarpa auzata. Pharm: Antifungal. Ref: N. Lindquist, et al, Tet. Lett., 1990, 31, 2389 N O S

O S

S

O H

980 Polycarpamine B Type: Di-, tri-, poly-sulfides. C14H19NO3S3 Yellow oil. Source: Ascidian Polycarpa auzata. Pharm: Antifungal. Ref: N. Lindquist, et al, Tet. Lett., 1990, 31, 2389 N O S

O S

S

O

981 Polycarpine Type: Di-, tri-, poly-sulfides. C22H24N6O2S2 Red rods (MeOH/CH2Cl2) or orange Amorph. solid, mp 201–204 °C. Source: Ascidians Polycarpa clavata (western Australia) and Polycarpa aurata (Chuuk State, Federated States of Micronesia). Pharm: Cytotoxic (Polycarpine dihydrochloride, HCT116, 0.9 μg/mL). Ref: H. Kang, et al, Tet. Lett., 1996, 37, 2369│S. A. Abas, et al, JOC, 1996, 61, 2709

2.4 S-contaning Compounds

411

NH2 O

N

N

S

S N

N

O

NH2

982 Rostratin A Type: Di-, tri-, poly-sulfides. C18H24N2O6S2 Gum, [α]D20 = –185° (c = 0.004, MeOH/ CH2Cl2). Source: Marine-derived fungus Exserohilum rostratum (whole broth). Pharm: Cytotoxic (HCT116, IC50 = 8.5 μg/mL). Ref: R. -X. Tan, et al, JNP, 2004, 67, 1374│ M. Saleem, et al, NPR, 2007, 24, 1142 (rev) HO

O

H S

N H OH

S

HO H

N H

O

OH

983 Rostratin B Type: Di-, tri-, poly-sulfides. C18H20N2O6S2 Gum, [α]D20 = –210° (c = 0.0004, MeOH/ CH2Cl2). Source: Marine-derived fungus Exserohilum rostratum. Pharm: Cytotoxic (HCT116, IC50 = 1.9 μg/mL). Ref: R. -X. Tan, et al, JNP, 2004, 67, 1374 O

H

O

5' 7'

9'

H OH

N

S S

OH H

N

7

9 5

O

H

O

984 Rostratin C Type: Di-, tri-, poly-sulfides. C20H24N2O8S2 Gum, [α]D20 = –167° (c = 0.002, MeOH/ CH2Cl2). Source: Marine-derived fungus Exserohilum rostratum. Pharm: Cytotoxic (HCT116, IC50 = 0.76 μg/mL). Ref: R. -X. Tan, et al, JNP, 2004, 67, 1374

412

2 Others

O

H

O

HO

O

H

7 9

S N

5'

N

9'

7'

H

S

O

H O

OH

O

5

985 Rostratin D Type: Di-, tri-, poly-sulfides. C18H20N2O6S4 Gum, [α]D20 = +108° (c = 0.007, MeOH/ CH2Cl2). Source: Marine-derived fungus Exserohilum rostratum. Pharm: Cytotoxic (HCT116, IC50 = 16.5 μg/mL). Ref: R. -X. Tan, et al, JNP, 2004, 67, 1374 O

H

O

OH

5' 7'

HS

9'

N

H OH

H

S

SH

N

S

7

9 5

O H

O

986 Shishijimicin A Type: Di-, tri-, poly-sulfides. C46H52N4O12S4 Source: Ascidian Didemnum proliferum. Pharm: Cytotoxic (3Y1, IC50 = 2.0 pg/mL, control Adriamycin, IC50 = 13000 pg/mL; HeLa, IC50 = 1.8 pg/mL, Adriamycin, IC50 = 17000 pg/mL; P388, IC50 = 0.47 pg/mL, Adriamycin, IC50 = 52000 pg/mL). Ref: N. Oku, et al, JACS, 2003, 125, 2044│ U. Galm, et al, Chem. Rev., 2005, 105, 739 O

O

O NH HO S

S

S

HO

O

S N H

N

4'

O OH OO

O 4''

NH O

2.4 S-contaning Compounds

413

987 Shishijimicin B Type: Di-, tri-, poly-sulfides. C45H50N4O12S3 Source: Ascidian Didemnum proliferum. Pharm: Cytotoxic (3Y1, IC50 = 3.1 pg/mL, control Adriamycin, IC50 = 13000 pg/mL; HeLa, IC50 = 3.3 pg/mL, Adriamycin, IC50 = 17000 pg/mL; P388, IC50 = 2.0 pg/mL, Adriamycin, IC50 = 52000 pg/mL). Ref: N. Oku, et al, JACS, 2003, 125, 2044│U. Galm, et al, Chem. Rev., 2005, 105, 739 O

O

O NH HO S

S

S

O

HO

O 4'

N

N H

OH OO

O 4''

NH

O

988 Shishijimicin C Type: Di-, tri-, poly-sulfides. C45H50N4O12S4 Source: Ascidian Didemnum proliferum. Pharm: Cytotoxic (3Y1, IC50 = 4.8 pg/mL, control Adriamycin, IC50 = 13000 pg/mL; HeLa, IC50 = 6.3 pg/mL, Adriamycin, IC50 = 17000 pg/mL; P388, IC50 = 1.7 pg/mL, Adriamycin, IC50 = 52000 pg/mL). Ref: N. Oku, et al, JACS, 2003, 125, 2044│U. Galm, et al, Chem. Rev., 2005, 105, 739 O

O

O NH HO S

S

S

HO

O

S N H

N

4'

O OH OO

O 4''

NH

O

414

2 Others

989 Tanjungide A Type: Di-, tri-, poly-sulfides. C16H16Br2N4O2S2 Source: Ascidian Diazona cf. formosa. Pharm: Cytotoxic (panel of HTCLs, < 1–2 μmol/L, potent). Ref: C. Murcia, et al, Mar. Drugs, 2014, 12, 1116 H 8Z

O H N

N H

Br

NH2

N H

Br

O

S

S

990 Tanjungide B Type: Di-, tri-, poly-sulfides. C16H16Br2N4O2S2 Source: Ascidian Diazona cf. formosa. Pharm: Cytotoxic (panel of HTCLs, < 1–2 μmol/L, potent). Ref: C. Murcia, et al, Mar. Drugs, 2014, 12, 1116 O H N

H N

8E

NH2

H

Br

O

S

S

N H

Br

991 1,2,4,6-Tetrathiepane Type: Di-, tri-, poly-sulfides. C3H6S4 mp 78–79 °C. Source: Red alga Chondria californica, mushroom Lentinus edodes. Pharm: Antibiotic. Ref: K. Morita, et al, CPB, 1967, 15, 998│S. J. Wratten, et al, JOC, 1976, 41, 2465

S S

S

S

992 Thiomarinol A Type: Di-, tri-, poly-sulfides. C30H44N2O9S2 Orange Cryst. (MeOH), mp 106–110 °C (dec), [α]D25 = +4.3° (c = 1, MeOH). Source: Marine bacterium Alteromonas rava. Pharm: Antimicrobial. Ref: H. Shiozawa, et al, J. Antibiolics, 1993, 46, 1834; 1995, 48, 907

2.4 S-contaning Compounds

415

OH

OH

OH

O

H 4

O H N

S

O

O

OH O

1''

N H

S

993 Thiomarinol C Type: Di-, tri-, poly-sulfides. C30H44N2O8S2 Yellow cryst., [α]D25 = –1.4° (MeOH). Source: Marine bacterium Alteromonas rava. Pharm: Antibacterial (gram-positive and -negative bacteria); isoleucyl transferase inhibitor; RNA synthetase inhibitor. Ref: H. Shiozawa, et al, J. Antibiot., 1995, 48, 907 S S OH HO

O

H

NH

O 7

O

O

N H

O

OH

994 Thiomarinol D Type: Di-, tri-, poly-sulfides. C31H46N2O9S2 [α]D25 = +1.5° (c = 0.8, MeOH). Source: Marine bacterium Alteromonas rava. Pharm: Isoleucyl transferase inhibitor; RNA synthetase inhibitor. Ref: H. Shiozawa, et al, J. Antibiot., 1997, 50, 449 S S O

OH

OH

NH

O

HO

N H

7

O

O

OH

O

995 Thiomarinol F Type: Di-, tri-, poly-sulfides. C31H44N2O9S2 [α]D25 = –1.66° (c = 0.8, MeOH). Source: Marine bacterium Alteromonas rava. Pharm: Isoleucyl transferase inhibitor; RNA synthetase inhibitor. Ref: H. Shiozawa, et al, J. Antibiot., 1997, 50, 449 S S OH

O

OH O

HO O

O

O

NH 7

N H

O

416

2 Others

996 1,2,4-Trithiolane Type: Di-, tri-, poly-sulfides. C2H4S3 Source: Red alga Chondria californica. Pharm: Antibiotic. Ref: S. J. Wratten, et al, JOC, 1976, 41, 2465 S S S

997 Varacin 8,9-Dimethoxy-6-benzopentathiepinethanamine Type: Di-, tri-, poly-sulfides. C10H13NO2S5 Light yellow powder, mp 258–260 °C. Source: Ascidians Lissoclinum vareau and Polycitor sp. Pharm: Antifungal (Candida albicans); cytotoxic (HCT116, IC90 = 0.05 μg/mL); damages DNA. Ref: B. S. Davidson, et al, JACS, 1991, 113, 4709│V. Behar, et al, JACS, 1993, 115, 7017│P. W. Ford, et al, JOC, 1993, 58, 4522│P. W. Ford, et al, JOC, 1994, 59, 5955│F. Trigalo, et al, Nat. Prod. Lett., 1994, 4, 101│F. D. Toste, et al, JACS, 1995, 117, 7261│T. N. Makarieva, et al, JNP, 1995, 58, 254│A. Greer, JACS, 2001, 123, 10379 O O

S

S

S

S

S

NH2

998 Varacin A 6,7-Dimethoxy-4-benzotrithioleethanamine Type: Di-, tri-, poly-sulfides. C10H13NO2S3 Source: Ascidian Polycitor sp. (Sea of Japan). Pharm: Antifungal (Candida albicans, 20 mm/0.1 μg); antibacterial (Bacillus subtilis, 20 mm/0.1 μg). Ref: T. N. Makarieva, et al, JNP, 1995, 58, 254 O O

S S S

NH2

2.4 S-contaning Compounds

417

999 Varacin B Type: Di-, tri-, poly-sulfides. C10H13NO3S3 Source: Ascidian Polycitor sp. (Sea of Japan). Pharm: Antifungal (Candida albicans, 20 mm/0.1 μg); antibacterial (Bacillus subtilis, 20 mm/0.1 μg). Ref: T. N. Makarieva, et al, JNP, 1995, 58, 254 O

O

O

S S S

H 2N

1000 Varacin C Type: Di-, tri-, poly-sulfides. C10H13NO3S3 Source: Ascidian Polycitor sp. (Sea of Japan). Pharm: Antifungal (Candida albicans, 20 mm/0.1 μg); antibacterial (Bacillus subtilis, 20 mm/0.1 μg). Ref: T. N. Makarieva, et al, JNP, 1995, 58, 254 O O

S S S O NH2

1001 Verticillin A Type: Di-, tri-, poly-sulfides. C30H28N6O6S4 Yellow needles (Py), mp 202–217 °C, [α]D = +703.7°, [α]D = +727° (dioxin). Source: Marine fungus Penicillium sp. CNC350. Pharm: Mycotoxin; cytotoxin. Ref: K. Katagiri, et al, J. Antibiot., Ser. B, 1970, 23, 420

O S H H S N N

N O OH OH

N N S H H S O

O N

418

2 Others

1002 Verticillin D Type: Di-, tri-, poly-sulfides. C32H32N6O8S4 Powder, mp 244–247 °C, [α]D = +220° (c = 0.1, MeOH). Source: Mangrove-derived fungus Bionectria ochroleuca from mangrove Sonneratia caseolaris (leaf, Hainan, China), terrestrial fungus (Gliocladium catenulatum). Pharm: Cytotoxic (L5178Y, 10 μg/mL, L5178Y Survival Rate = 0.5%, EC50 < 0.1 μg/mL, control Kahalalide F, EC50 = 6.40 μg/mL). Ref: B. K. Joshi, et al, JNP, 1999, 62, 730│W. Ebrahim, et al, Mar. Drugs, 2012, 10, 1081 HO O S S H H N N

N O OH OH

N N H H S S O

O N

HO

1003 (+)-Adociaquinone A Type: Sulfone and sulfoxide. C22H17NO6S Yellow solid, mp > 300 °C, [α]D = +25° (c = 0.075, DMSO). Source: Sponge Adocia sp. (Trukese). Pharm: Cytotoxic. Ref: F. J. Schmitz, et al, JOC, 1988, 53, 3922│N. Harada, et al, Tetrahedron: Asymmetry, 1995, 6, 375 HN O

S

O O

O

3

O O

1004 (+)-Adociaquinone B Type: Sulfone and sulfoxide. C22H17NO6S Yellow solid, mp > 300 °C, [α]D = +22° (c = 0.085, DMSO). Source: Sponge Adocia sp. (Trukese). Pharm: Cytotoxic. Ref: F. J. Schmitz, et al, JOC, 1988, 53, 3922│N. Harada, et al, Tetrahedron: Asymmetry, 1995, 6, 375

2.4 S-contaning Compounds

O

419

O S

O

NH

O

3

O O

1005 (R)-Agelasidine A 2-[[(1-Ethenyl-1,5,9-trimethyl-4,8-decadienyl)sulfonyl]ethyl]guanidine Type: Sulfone and sulfoxide. C18H33N3O2S Unstable yellow oil, [α]D20 = –14.5° (c = 1.5, CHCl3). Source: Sponges Agelas nakamurai and Agelas sp. (Palau, Western Caroline Island, Oceanin) and Agelas clathrodes. Pharm: Antispasmodic; antibacterial. Ref: H. Nakamura, et al, Tet. Lett., 1983, 24, 4105│R. J. Capon, et al, JACS, 1984, 106, 1819│H. Nakamura, et al, JOC, 1985, 50, 2494│Y. Ichikawa, et al, JCS Perkin 1, 1992, 1497│M. A. Medeiros, et al, Z. Naturforsch., C, 2006, 61, 472 H N

NH NH2

O S

O

1006 Ascidiathiazone A Type: Sulfone and sulfoxide. C12H8N2O6S Yellow powder, mp 155 °C (dec). Source: Ascidian Aplidium sp. (New Zealand). Pharm: Anti-inflammatory (hmn neutrophil free radical inhibition in vitro and in vivo, IC50 = 0.44–1.55 μmol/L, MMOA: superoxide anion inhibition). Ref: A. N. Pearce, et al, JNP, 2007, 70, 936 O H N

O N

OH

S O

O

O

1007 Ascidiathiazone B Type: Sulfone and sulfoxide. C12H6N2O6S Pink powder, mp 280 °C (dec). Source: Ascidian Aplidium sp. (New Zealand). Pharm: Anti-inflammatory (hmn neutrophil

420

2 Others

free radical inhibition in vitro and in vivo, IC50 = 0.44–1.55 μmol/L, MMOA: superoxide anion inhibition). Ref: A. N. Pearce, et al, JNP, 2007, 70, 936 O

H N S O

OH

N O

O

O

1008 Conicaquinone A Type: Sulfone and sulfoxide. C18H19NO4S Source: Ascidian Aplidium conicum. Pharm: Cytotoxic (C6, IC50 ≈ 3 μg/mL; RBL-2H3, IC50 ≈ 76 μg/mL). Ref: A. Aiello, et al, EurJOC, 2003, 898 O

H N S

O

O

O

1009 Conicaquinone B Type: Sulfone and sulfoxide. C18H19NO4S Source: Ascidian Aplidium conicum. Pharm: Cytotoxic (C6, IC50 ≈ 8 μg/mL; RBL-2H3, IC50 ≈ 78 μg/mL). Ref: A. Aiello, et al, EurJOC, 2003, 898 O

H N

S O

O

O

1010 Echinosulfone A Type: Sulfone and sulfoxide. C17H10Br2N2O4S Orange oil. Source: Sponge Echinodictyum sp. (Southern Australia). Pharm: Antibacterial. Ref: S. P. B. Ovenden, et al, JNP, 1999, 62, 1246 O

Br

O S

N HO

O

Br N H

2.4 S-contaning Compounds

421

1011 4-(Ethenylsulfonyl)-2-butanone Cladiosulfone; Austrasulfone Type: Sulfone and sulfoxide. C6H10O3S Light yellow oil, [α]D25 = −8° (c = 1.7, CHCl3). Source: Soft coral Cladiella australis (Southern Taiwan). Pharm: Neuroprotective (hmn dopaminergic neuron assay model of Parkinson’s disease). Ref: Z. -H. Wen, et al, Eur. JMC, 2010, 45, 5998 O

O S O

1012 1-Ethyl-4-methylsulfone-β-carboline 1-Ethyl-4-(methylsulfonyl)-9H-pyrido[3,4-b]indole Type: Sulfone and sulfoxide. C14H14N2O2S Pale green oil. Source: Bryozoan Cribricellina cribraria (New Zealand). Pharm: Cytotoxic (P388, IC50 > 12500 ng/mL); antibacterial (Eschichia coli, MIC > 60 μg/disc; Bacillus subtilis, MIC = 30–60 μg/disc; Pseudomonas aeruginosa, MIC > 60 μg/disc); antifungal (Candida albirnns, MIC > 60 μg/disc; Trichophyton mtagropbytes, MIC = 30–60 μg/disc; Cladzspwum resina, MIC > 60 μg/disc). Ref: M. R. Prinsep, et al, JNP, 1991, 54, 1068 O

S

O

N

N H

1013 Eudistomin K sulphoxide Type: Sulfone and sulfoxide. C14H16BrN3O2S Light yellow oil, [α]D25 = –3.3° (c = 0.09, MeOH). Source: Ascidian Ritterella sigillinoides. Pharm: Antiviral. Ref: R. J. Lake, et al, Tet. Lett., 1988, 29, 2255; 4971 10

N O Br

13

N H

H H2 N

1

S O

1014 Euthyroideone A Type: Sulfone and sulfoxide. C12H13BrN2O3S mp 245 °C. Source: Bryozoan Euthyroides episcopalis (New Zealand). Pharm: Cytotoxic (P388, IC50 > 12500 ng/mL). Ref: B. D. Morris, et al, JOC, 1998, 63, 9545

422

2 Others

N

8

O

O

7

S

Br

N H

2 3

O

1015 Euthyroideone B Type: Sulfone and sulfoxide. C12H11BrN2OS3 mp 244 °C. Source: Bryozoan Euthyroides episcopalis (New Zealand). Pharm: Cytotoxic (P388, IC50 > 12500 ng/mL); cytotoxic (antiviral/cytotoxicity assay, BSC-1 derived from African Green Monkey kidney cells, weakly). Ref: B. D. Morris, et al, JOC, 1998, 63, 9545

N O

S

O

N H

Br O

1016 Euthyroideone C Type: Sulfone and sulfoxide. C12H11BrN2OS3 Source: Bryozoan Euthyroides episcopalis (New Zealand). Pharm: Cytotoxic (P388, IC50 > 12500 ng/mL). Ref: B. D. Morris, et al, JOC, 1998, 63, 9545

N

O

O S N H

Br O

1017 Lissoclin disulfoxide Type: Sulfone and sulfoxide. C26H38N2O6S4 Yellow solid. Source: Ascidian Lissoclinum sp. Pharm: IL-8 receptors inhibitor. Ref: A. D. Patil, et al, Nat. Prod. Lett., 1997, 10, 225 N

N O

S

S

S

10 5

O

S O

O

O O

2.4 S-contaning Compounds

423

1018 5-(Methoxymethyl)-4-[(methylsulfonyl)methyl]-1,2,3-benzenetriol Type: Sulfone and sulfoxide. C10H14O6S Powder, mp 164.5–166.5 °C. Source: Red alga Grateloupia filicina. Pharm: Antibacterial (moderate). Ref: H. Nozaki, et al, Agric. Biol. Chem., 1988, 52, 3229 O S HO

OH

O

O

OH

1019 1-Oxo-1,2,4-trithiolane Type: Sulfone and sulfoxide. C2H4OS3 Source: Red alga Chondria californica. Pharm: Antibiotic. Ref: S. J. Wratten, et al, JOC, 1976, 41, 2465 –

O

+

S

S

S

1020 4-Oxo-1,2,4-trithiolane Type: Sulfone and sulfoxide. C2H4OS3 mp 76–77 °C. Source: Red alga Chondria californica. Pharm: Antibiotic. Ref: S. J. Wratten, et al, JOC, 1976, 41, 2465 S S

+

S

–

O

1021 Phakellistatin 14 Type: Sulfone and sulfoxide. C36H53N7O10S Amorph. powder, mp 189–191 °C, [α]D25 = – 64.9° (c = 0.28, MeOH). Source: Sponge Phakellia sp. Pharm: Cytotoxic (P388, ED50 = 5 μg/mL; a panel of hmn cancer cells, GI50 = 0.75–3.4 μg/mL, moderate). Ref: G. R. Pettit, et al, JNP, 2005, 68, 60

OO

HN O N

HN

O

H O

O

NH

O

O

N H NH

H N

S O

O

424

2 Others

1022 Thiaplakortone A Type: Sulfone and sulfoxide. C12H11N3O4S Stable orange-brown amorphous solid (trifluoroacetate salt). Source: Sponge Plakortis lita (Tydeman Reef, Queensland, Australia). Pharm: Antiplasmodial (DSPF 3D7, IC50 = 51 nmol/L; DRPF Dd2, IC50 = 6.6 nmol/L; HEK-293, IC50 = 3900 nmol/L; SI (3D7) = 76, SI (Dd2) = 591). Ref: R. A. Davis, et al, JOC, 2013, 78, 9608 O

O

O

NH2

S

N H

N H O

1023 Thiaplakortone B Type: Sulfone and sulfoxide. C12H13N3O4S Stable orange-brown amorphous solid (trifluoroacetate salt). Source: Sponge Plakortis lita (Tydeman Reef, Queensland, Australia). Pharm: Antiplasmodial (DSPF 3D7, IC50 = 650 nmol/L; drpf Dd2, IC50 = 92 nmol/L; HEK-293, IC50 > 40000 nmol/L; SI (3D7) > 62, SI (Dd2) > 435). Ref: R. A. Davis, et al, JOC, 2013, 78, 9608 O

O

O NH2

S N H

N H

O

1024 Thiaplakortone C Type: Sulfone and sulfoxide. C14H13N3O6S Stable orange-brown amorphous solid (trifluoroacetate salt), [α]D27 = +56 °C (c = 0.025, CH3OH), [α]D25 = +129° (c = 0.007, 0.5M HCl). Source: Sponge Plakortis lita (Tydeman Reef, Queensland, Australia). Pharm: Antiplasmodial (DSPF 3D7, IC50 = 309 nmol/L; DRPF Dd2, IC50 = 171 nmol/L; HEK-293, IC50 > 40000 nmol/L; SI (3D7) > 129, SI (Dd2) > 233). Ref: R. A. Davis, et al, JOC, 2013, 78, 9608 O O

O

NH

S

N H

OH 11S

O

N H O

2.4 S-contaning Compounds

425

1025 Thiaplakortone D Type: Sulfone and sulfoxide. C14H13N3O6S Stable orange-brown amorphous solid (trifluoroacetate salt), [α]D28 = +80 °C (c = 0.025, CH3OH), [α]D25 = +143° (c = 0.007, 0.5M HCl). Source: Sponge Plakortis lita (Tydeman Reef, Queensland, Australia). Pharm: Antiplasmodial (DSPF 3D7, IC50 = 279 nmol/L; DRPF Dd2, IC50 = 159 nmol/L; HEK-293, IC50 > 80000 nmol/L; SI (3D7) > 285, SI (Dd2) > 500). Ref: R. A. Davis, et al, JOC, 2013, 78, 9608 O O

H N

N H N H

S O

OH 11S

O

O

1026 Thiaplidiaquinone A Type: Sulfone and sulfoxide. C34H41NO6S Source: Ascidian Aplidium conicum. Pharm: Cytotoxic (JurKat, IC50 ≈ 3 μmol/L); ROS inducer (JurKat, induces strongly production of ROS). Ref: A. Aiello, et al, JMC, 2005, 48, 3410 OH O

H N

O

S O

O

O

1027 Thiaplidiaquinone B Type: Sulfone and sulfoxide. C34H41NO6S Source: Ascidian Aplidium conicum. Pharm: Cytotoxic (JurKat, IC50 ≈ 3 μmol/L); ROS inducer (JurKat, induces strongly production of ROS). Ref: A. Aiello, et al, JMC, 2005, 48, 3410

426

2 Others

OH O

H N

O

S O

O

O

1028 Thiolsulfonate Type: Sulfone and sulfoxide. C3H6O2S4 mp 154–155 °C. Source: Red alga Chondria californica. Pharm: Antibiotic. Ref: S. J. Wratten, et al, JOC, 1976, 41, 2465 O S

S S

O

S

1029 Thiomarinol B Type: Sulfone and sulfoxide. C30H44NO11S2 [α]D25 = +7.7° (1-propanol). Source: Marine bacterium Alteromonas rava. Pharm: Antibacterial (gram-positive and negative bacteria). Ref: H. Shiozawa, et al, J. Antibiotics, 1995, 48, 907 O

O S

S OH HO

OH

O

H

NH

O 7

O

O

N H

O

OH

2.5 As-contaning compounds 1030 Arsenobetaine (Carboxymethyl)trimethylarsonium hydroxide inner salt Type: As-contaning compounds. C5H11AsO2 Deliquescent cryst. (Me2CO/MeOH), mp 204–210 °C (dec). Source: Rock lobster Panuliris longipes cygnus (Australia), and occurs in algae,

2.6 Miscellaneous

427

lobsters, sharks and dogfishes etc. Pharm: Toxin; LD50 (mus, orl) = 10000 mg/kg. Ref: J. S. Edmonds, et al, Tet. Lett., 1977, 1543 O +

As

–

O

2.6 Miscellaneous 1031 Ferrineoaspergillin Type: Miscellaneous. C36H57FeN6O6 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 –

O N

Fe N

3+

O –

O N

N

O –

O

1032 Mozukutoxin A (1-Ethoxyethyl) hydroperoxide Type: Miscellaneous. C4H10O3 Oil. Source: Ascidians Cladosiphon okamuranus, Halocynthia roretzi and Styela plicata. Pharm: Highly toxic; LD50 (mice) = 250 mg/kg. Ref: A. Nakamura, et al, Tet. Lett., 1991, 32, 4355

HO

O

O

Index 1 Compound Name and Synonym Index This index lists in alphabetical order all active compound’s 1,122 entry names including both 1,032 key names and 90 synonym names contained in the bodies of compound entries. A equal sign (=) and compound code number (from 1 to 1,032) follow the name immediately for locating the compound in the “Handbook of Active Marine Natural Products Volume 8” 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 Aceneuramic acid = 893. N-(3-Acetoxy-2,4-dimethyldodecanoyl) proline = 888. N-Acetylneuraminic acid = 893. Achillein = 859. Aciculitin A = 259. Aciculitin B = 260. Aciculitin C = 261. Acyclodidemnin A = 171. Adenine deoxyriboside = 905. Adenosine = 904. (ADMAdda5)Microcystin LHar = 262. (ADMAdda5)Microcystin LR = 263. (+)-Adociaquinone A = 1003. (+)-Adociaquinone B = 1004. Aeruginosin 101 = 129. Aeruginosin 102A = 130. Aeruginosin 102B = 131. Aeruginosin 103A = 132. Aeruginosin 205A = 133. Aeruginosin 205B = 134. Aeruginosin 298A = 135. Aeruginosin 89B = 136. Aeruginosin 98A = 137. Aeruginosin 98B = 138. Aeruginosin 98C = 139. Aeruginosin KY608 = 140. Aeruginosin KY642 = 141. (R)-Agelasidine A = 1005. α-Allokainic acid = 858. α-Allokaininic acid = 858. Almiramide A = 172. Almiramide B = 173. Almiramide C = 174. Alternaramide = 487. Alternarosin A = 1.

https://doi.org/10.1515/9783110655834-003

Alterobactin A = 488. Alterobactin B = 175. 3-Amino-3-deoxy-D-glucose = 892. 6-Amino-8,9-dimethoxy-N,N-dimethyl7-(methylthio)benzopentathiepin = 931. 6-(2-Aminoethyl)-3,4-dimethoxybenzotrithiane = 918. 9-(2-Aminoethyl)-6-methoxy-7benzopentathiepinol = 969. Amphibactin B = 176. Amphibactin S = 177. Amphibactin T = 178. Anabaenopeptin A = 465. Anabaenopeptin B = 466. Anabaenopeptin C = 467. Anabaenopeptin D = 468. Anabaenopeptin G = 469. Anabaenopeptin H = 470. Anabaenopeptin I = 471. Anabaenopeptin J = 472. Anabaenopeptin T = 473. Antibiotic 1656B = 155. Antibiotic B 90063 = 919. Antibiotic FR 49175 = 10. Antibiotic IB 01212 = 489. Antibiotic K 26 = 149. Antibiotic KA 7038I = 898. Antibiotic MK 349A = 295. Antibiotic PM 93135 = 693. Antibiotic RK-F 1010 = 124. Antibiotic Sch 54796 = 2. Antillatoxin = 716. Antillatoxin B = 717. Aplidine = 490. Apratoxin A = 770. Apratoxin A sulfoxide = 771. Apratoxin B = 772.

430

Index 1 Compound Name and Synonym Index

Apratoxin C = 773. Apratoxin D = 774. Apratoxin E = 775. Apratoxin F = 776. Apratoxin G = 777. Apratoxin H = 778. Aquachelin I = 179. Aquachelin J = 180. Arenamide A = 718. Arenamide B = 719. Arenamide C = 720. Arenastatin A = 515. Arsenobetaine = 1030. Ascidiacyclamide = 409. Ascidiathiazone A = 1006. Ascidiathiazone B = 1007. (D-Asp,ADMAdda5)Microcystin LR = 264. Aspereline A = 239. Aspereline B = 240. Aspereline C = 241. Aspereline D = 242. Aspereline E = 243. Aspereline F = 244. Aspergilazine A = 3. Aspergillamide A (1998) = 872. Aspergillipeptide C = 265. Aspergillusol A = 873. Asperterrestide A = 266. Aspochracin = 267. Astebatherioside B = 901. Astebatherioside C = 902. Astebatherioside D = 903. Aurantiamine = 4. Aurilide = 491. Aurilide B = 492. Aurilide C = 493. Austrasulfone = 1011. Axinastatin 1 = 268. Axinastatin 2 = 269. Axinastatin 3 = 270. Axinastatin 4 = 271. Axinastatin 5 = 272. Axinellin A = 273. Axinellin B = 274. (+)-Azonazine = 5. Azumamide A = 275. Azumamide E = 276.

B Bacillistatin 1 = 494. Bacillistatin 2 = 495. Bacillusamide A = 6. Bacillus pumilus KMM 1364 Lipodepsipeptide A = 721. Bacillus pumilus KMM 1364 Lipodepsipeptide B = 722. Bacillus pumilus KMM 1364 Lipodepsipeptide C = 723. Bacillus pumilus KMM 1364 Lipodepsipeptide D = 724. Bacillus pumilus KMM 1364 Lipodepsipeptide E = 725. Bacillus pumilus KMM 1364 Lipodepsipeptide F = 726. Bacillus pumilus KMM 1364 Lipodepsipeptide G = 727. Barettin = 7. Belamide A = 150. Benarthin = 120. (R,Z)-3-Benzylidene-6-(hydroxymethyl)1,4-dimethyl-6-(methylthio)2,5- piperazinedione = 8. Betonicine = 859. 4,10-Bis(2-aminoethyl)-1,7-dimethoxydibenzo [c,g][1,2,5,6]-tetrathiocin- 2,8-diol = 971. Bis(6-bromo-2-tryptaminyl) disulfide = 920. Bis(dethio)bis-(methylthio)-5a,6didehydrogliotoxin = 9. Bisdethiobis(methylthio)gliotoxin = 10. Bis(dethio)-10a-methylthio-3a-deoxy3,3a-didehydrogliotoxin = 11. Bisebromoamide = 181. Bistratamide A = 410. Bistratamide B = 411. Bistratamide D = 412. Bistratamide E = 413. Bistratamide F = 414. Bistratamide G = 415. Bistratamide H = 416. Bistratamide I = 417. Bogorol A = 245. Bouillomide A = 799. Bouillomide B = 800. Bouillonamide = 496. Brevianamide F = 12. Brevianamide K = 13.

Index 1 Compound Name and Synonym Index

Brevianamide S = 14. Brevianamide W = 15. Brocazine A = 921. Brocazine B = 922. Brocazine E = 923. Brocazine F = 924. Bromoalterochromide A = 497. Bromobenzisoxazolone barettin = 16. Brunsvicamide B = 474. Brunsvicamide C = 475. Buccinulin = 895. C Callipeltin A = 498. Callipeltin B = 499. Callipeltin C = 182. Callipeltin F = 183. Callipeltin G = 184. Callipeltin H = 185. Callipeltin I = 186. Callipeltin J = 187. Callipeltin K = 188. Callyaerin A = 277. Callyaerin B = 278. Callyaerin C = 279. Callyaerin D = 280. Callyaerin E = 281. Callyaerin F = 282. Callyaerin G = 283. Callyaerin H = 284. Calyxamide A = 439. Calyxamide B = 440. (Carboxymethyl)trimethylarsonium hydroxide inner salt = 1030. Carmabin A = 189. Carmaphycin A = 151. Carmaphycin B = 152. Carnosadine = 860. Celebeside A = 500. Celebeside C = 501. trans,trans-Ceratospongamide = 418. cis,cis-Ceratospongamide = 419. Cereulide = 502. Chlorodysinosin A = 142. Chloropullularin E = 285. Chondramide A = 503. Chrysogenazine = 17. Citronamide A = 190. Citronamide B = 191.

Cladiosulfone = 1011. Clonostachysin A = 286. Clonostachysin B = 287. Cocosamide A = 288. Cocosamide B = 289. Coibamide A = 504. Comoramide A = 420. Comoramide B = 441. Conicaquinone A = 1008. Conicaquinone B = 1009. Cordyheptapeptide C = 290. Cordyheptapeptide E = 291. Cotteslosin B = 292. Criamide A = 192. Criamide B = 193. Cristatumin A = 18. Cristatumin B = 19. Cristatumin F = 20. Cryptoechinuline D = 21. (−)-Cryptoechinuline D = 22. (+)-Cryptoechinuline D = 23. Cryptophycin 1 = 505. Cryptophycin 16 = 506. Cryptophycin 17 = 507. Cryptophycin 175 = 508. Cryptophycin 176 = 509. Cryptophycin 18 = 510. Cryptophycin 19 = 511. Cryptophycin 2 = 512. Cryptophycin 21 = 513. Cryptophycin 23 = 514. Cryptophycin 24 = 515. Cryptophycin 26 = 516. Cryptophycin 28 = 517. Cryptophycin 29 = 518. Cryptophycin 3 = 519. Cryptophycin 30 = 520. Cryptophycin 31 = 521. Cryptophycin 4 = 522. Cryptophycin 40 = 523. Cryptophycin 43 = 524. Cryptophycin 45 = 525. Cryptophycin 46 = 526. Cryptophycin 49 = 527. Cryptophycin 50 = 528. Cryptophycin 52 = 529. Cryptophycin 54 = 530. Cryptophycin A = 505. Cryptophycin B = 512.

431

432

Index 1 Compound Name and Synonym Index

Cryptophycin C = 519. Cryptophycin D = 522. Cupolamide A = 293. Cyanopeptolin 954 = 801. Cyanopeptolin 963 A = 802. Cyclocinamide A = 294. Cyclodidemnamide = 421. Cycloforskamide = 442. Cyclo(2-hydroxy-Pro-R-Leu) = 24. Cyclo-(4-S-hydroxy-R-proline-R-isoleucine) = 25. (3S,7R,8aS)-Cyclo(4-hydroxyprolylleucyl) = 26. Cyclo(4-hydroxy-S-Pro-S-Trp) = 27. Cyclo-(D-cis-Hyp-L-Phe) = 28. Cyclo(L-Ile-L-Pro) = 29. Cyclo(isoleucylprolylleucylprolyl) = 295. Cyclo(leucylprolyl) = 30. Cyclo(L-Leu-L-Pro) = 30. Cyclomarin A = 296. (3S,8αS)-Cyclo(prolylvalyl) = 31. Cyclo(D-Pro-D-Phe) = 32. (all-L)-Cyclo(Pro-Val)2 = 297. Cyclotheonamide A = 298. Cyclotheonamide B = 299. Cyclotheonamide C = 300. Cyclotheonamide D = 301. Cyclotheonamide E = 302. Cyclotheonamide E2 = 303. Cyclotheonamide E3 = 304. Cyclo(D-Tyr-D-Pro) = 33. D Deacetylhectochlorin = 779. (E)-Dehydroapratoxin A = 780. Dehydrodidemnin B = 490. (R,R)-16,17-Dehydrodiscorhabdin W = 925. (S,S)-16,17-Dehydrodiscorhabdin W = 926. 8,9-Dehydrotryprostatin A = 60. 33-Demethoxy-33-(methylsulfinyl) theonellapeptolide Id = 531. 33-Demethoxytheonellapeptolide Ie = 532. 12-Demethyl-12-oxo-eurotechinulin B = 34. 2ʹ-Deoxyadenosine = 905. Deoxybisdethiobis(methylthio)gliotoxin = 35. 6-Deoxy-5a,6-didehydrogliotoxin = 927. 5ʹ-Deoxy-5-iodotubercidin = 906. Deoxymajusculamide D = 194. Deoxymycelianamide = 36. 22ʹ-Deoxythiocoraline = 533. 11-Deoxyverticillin A = 928.

Depsipeptide 1962A = 534. Desacetylmicrocolin B = 195. Desmethoxymajusculamide C = 535. Desmethylisaridin C1 = 536. Desmethylisaridin G = 537. Destruxin E chlorohydrin = 484. (S)-2,5-Diaminopentanoic acid = 857. Dibenarthin = 153. 5,6-Dibromoabrine = 861. Dictyonamide A = 246. Didehydroechinulin B = 37. 5a,6-Didehydrogliotoxin = 929. Didemnin A = 538. epi-Didemnin A1 = 539. Didemnin B = 540. Didemnin C = 541. Didemnin H = 542. Didemnin M = 542. Didemnin N = 543. 11,11ʹ-Dideoxyverticillin A = 930. 8,9-Dihydrobarettin = 38. Dihydrocarneamide A = 39. Dihydrocryptoechinulin D = 40. Dihydrocyclotheonamide A = 305. N-[[3,4-Dihydro-3S-hydroxy-2S-methyl2-(4′R-methyl-3′S-pentenyl)-2H-1benzopyran-6-yl]carbonyl]-threonine = 862. Dihydroneochinulin B = 41. 3,4-Dihydro-1,6,7-trimethoxy-N,N-dimethyl8-(methyldithio)-1H-2-benzothiopyran5-amine = 979. 12,13-Dihydroxyfumitremorgin C = 42. 8,9-Dihydroxyisospirotryprostatin A = 43. Diketopiperazine dimer = 44. Diketopiperazine V = 15. 8,9-Dimethoxy-6benzopentathiepinethanamine = 997. 6,7-Dimethoxy-4-benzotrithioleethanamine = 998. 3,4-Dimethoxy-6-(2ʹ-N,N-dimethylaminoethyl)5-(methylthio)benzotrithiane = 918. 9-[2-(Dimethylamino)ethyl]-7-methoxy6-benzopentathiepinol = 968. 9ξ-O-2(2,3-Dimethylbut-3-enyl)brevianamide Q = 45. N,N-Dimethyl-5-(methylthio)varacin = 931. (6Z)-6-{[2-(1,1-Dimethylprop-2-en-1-yl)5,7-bis(3-methylbut-2-en-1-yl)-1H-indol-3-yl] methylene}piperazine-2,3,5-trione = 34.

Index 1 Compound Name and Synonym Index

(3Z,6S)-3-{{2-(1,1-Dimethylprop-2-en-1-yl)7-[(2E)-4-hydroxy-3-methylbut-2-en-1-yl]1H-indol-3-yl}methylidene}-6methylpiperazine-2,5- dione = 115. (3Z,6S)-3-{{2-(1,1-Dimethylprop-2-en-1-yl)7-{[3-(hydroxymethyl)-3-methyloxiran2-yl]methyl}-1H-indol-3-yl}methylidene}6-methyl- piperazine-2,5-dione = 116. Discobahamin A = 403. Discobahamin B = 404. Discodermin A = 306. Discodermin B = 307. Discodermin C = 308. Discodermin D = 309. Discodermin E = 310. Discodermin F = 311. Discodermin G = 312. Discodermin H = 313. Dolastatin 10 = 196. Dolastatin 11 = 544. Dolastatin 12 = 545. Dolastatin 13 = 803. Dolastatin 14 = 728. Dolastatin 15 = 197. Dolastatin 16 = 546. Dolastatin 17 = 547. Dolastatin 3 = 443. Dolastatin C = 874. Dolastatin D = 548. Dolastatin G = 549. Dolastatin I = 422. Doliculide = 550. Dominicin = 314. Doridosine = 907. Dragomabin = 198. Dragonamide = 199. Dragonamide A = 199. Dragonamide E = 200. Dysamide A = 46. Dysinosin A = 143. Dysinosin B = 144. Dysinosin C = 145. Dysinosin D = 146. E Echinobetaine A = 869. Echinosulfone A = 1010. Efrapeptin Eα = 247. Efrapeptin F = 248.

433

Efrapeptin G = 249. Efrapeptin J = 250. Elisidepsin = 577. Emericellamide A = 551. Emericellamide B = 552. Enniatin B = 463. Enniatin B4 = 464. Enniatin D = 464. Eodoglucomide A = 890. Eodoglucomide B = 891. Erinacean = 870. 4-(Ethenylsulfonyl)-2-butanone = 1011. 2-[[(1-Ethenyl-1,5,9-trimethyl-4,8-decadienyl) sulfonyl]ethyl]guanidine = 1005. (1-Ethoxyethyl) hydroperoxide = 1032. 1-Ethyl-4-methylsulfone-β-carboline = 1012. 1-Ethyl-4-(methylsulfonyl)-9H-pyrido[3,4-b] indole = 1012. Ethyl tumonoate A = 875. Etzionin = 47. Eudistomin K sulphoxide = 1013. Euryjanicin A = 315. Euthyroideone A = 1014. Euthyroideone B = 1015. Euthyroideone C = 1016. Exumolide A = 553. Exumolide B = 554. F Fellutamide A = 154. Fellutamide B = 155. Fellutamide C = 156. Fellutamide F = 157. Ferrineoaspergillin = 1031. Floridoside = 900. G Gageostatin A = 838. Gageostatin B = 839. Gageostatin C = 840. Gageotetrin A = 841. Gageotetrin B = 842. Gageotetrin C = 843. 2-O-α-D-Galactopyranosylglycerol = 900. Geodiamolide A = 555. Geodiamolide B = 556. Geodiamolide C = 557. Geodiamolide D = 558. Geodiamolide E = 559.

434

Index 1 Compound Name and Synonym Index

Geodiamolide F = 560. Geodiamolide G = 561. Geodiamolide H = 562. Ggeopeptide A = 844. Ggeopeptide B = 845. Ggeopeptide C = 846. Ggeopeptide D = 847. Gliocladride = 48. Gliocladride A = 49. Gliocladride B = 50. Gliotoxin = 932. Gliotoxin = 933. Gliotoxin G = 934. Golmaenone = 51. Grassypeptolide A = 781. Grassypeptolide B = 782. Grassypeptolide C = 783. Grassypeptolide D = 784. Grassypeptolide E = 785. Grassypeptolide F = 786. Grassypeptolide G = 787. Grassystatin A = 251. Grassystatin B = 252. Grassystatin C = 253. Guangomide A = 563. Guangomide B = 564. Guineamide G = 565. Gymnangiamide = 201. H Haliclamide = 566. Halicylindramide A = 567. Halicylindramide B = 568. Halicylindramide C = 569. Halicylindramide D = 570. Halicylindramide E = 254. Halipeptin A = 788. Halobacillin = 729. Halovir A = 202. Halovir B = 203. Halovir C = 204. Halovir D = 205. Halovir E = 206. Hantupeptin A = 571. Hantupeptin B = 572. Hantupeptin C = 573. Hassallidin A = 730. Hectochlorin = 789. Hemiasterlin = 158.

Hemiasterlin A = 159. Hemiasterlin B = 160. Hemiasterlin C = 161. Hoiamide A = 790. Hoiamide B = 791. Hoiamide C = 855. Homocereulide = 574. Homodolastatin 16 = 316. Homodolastatin 3 = 444. Homophymine A = 731. Homophymine A1 = 732. Homophymine B = 733. Homophymine B1 = 734. Homophymine C = 735. Homophymine C1 = 736. Homophymine D = 737. Homophymine D1 = 738. Homophymine E = 739. Homophymine E1 = 740. Hormothamnin A = 317. N-(3-Hydroxy-2,4-dimethyl-4-dodecenoyl) proline = 887. 2′ξ-Hydroxy-fumitremorgin B Δ3′-Isomer (1) = 52. 2′ξ-Hydroxy-fumitremorgin B Δ3′-Isomer (2) = 53. 9-Hydroxyfumitremorgin C = 54. 9-Hydroxyfumitremorgin C = 55. (+)-5-Hydroxy-4-(4-hydroxy-3-methoxyphenyl)4-(2-imidazolyl)-1,2,3-trithiane = 935. (–)-5-Hydroxy-4-(4-hydroxy-3-methoxyphenyl)4-(2-imidazolyl)-1,2,3-trithiane = 936. 14-Hydroxyterezine D = 56. Hymenamide G = 272. Hymenamide H = 369. Hymenistatin 1 = 318. I Ibu-epi-demethoxylyngbyastatin 3 = 575. (Indole-N-isoprenyl)-tryptophan-valine = 57. Indotertine B = 58. Isaridin G = 576. Isokahalalide F = 577. Isolissoclinotoxin B = 968. Istamycin A = 898. Istamycin B = 899. Itralamide B = 578. J Janolusimide = 162. Jaspamide = 579.

Index 1 Compound Name and Synonym Index

Jaspamide B = 580. Jaspamide C = 581. Jaspamide D = 582. Jaspamide E = 583. Jaspamide F = 584. Jaspamide G = 585. Jaspamide H = 586. Jaspamide J = 587. Jaspamide K = 588. Jaspamide L = 589. Jaspamide M = 590. Jaspamide N = 591. Jaspamide O = 592. Jaspamide P = 593. 21-epi-Jaspamide P = 594. Jaspamide Q = 595. Jaspamide R = 596. Jaspamide S = 598. Jaspamide V = 599. Jaspamide Z3 = 165. Jaspamide Z4 = 166. Jasplakinolide = 579. Jasplakinolide B = 580. Jasplakinolide C = 581. Jasplakinolide D = 582. Jasplakinolide E = 583. Jasplakinolide F = 584. Jasplakinolide G = 585. Jasplakinolide H = 586. Jasplakinolide J = 587. Jasplakinolide K = 588. Jasplakinolide L = 589. Jasplakinolide M = 590. Jasplakinolide N = 591. Jasplakinolide O = 592. Jasplakinolide P = 593. 21-epi-Jasplakinolide P = 594. Jasplakinolide Q = 595. (–)-Jasplakinolide R = 596. (+)-Jasplakinolide R1 = 597. Jasplakinolide S = 598. (+)-Jasplakinolide V = 599. (+)-Jasplakinolide W = 600. (+)-Jasplakinolide Z1 = 163. (+)-Jasplakinolide Z2 = 164. (+)-Jasplakinolide Z3 = 165. (–)-Jasplakinolide Z4 = 166. JBIR-25 = 873. Jimycin A = 601.

Jimycin B = 602. Jimycin C = 603. K Kahalalide A = 604. Kahalalide F = 741. Kahalalide R = 742. Kailuin A = 743. Kailuin B = 744. Kailuin C = 745. Kailuin D = 746. Kailuin E = 747. (–)-Kainic acid = 863. Kapakahine A = 319. Kapakahine B = 320. Kapakahine C = 321. Kapakahine E = 322. Keenamide A = 445. Kelletinin A = 895. Kelletinin I = 894. Kelletinin II = 896. Kempopeptin A = 605. Kempopeptin B = 606. Kendarimide A = 255. Keramamide A = 476. Keramamide E = 405. Keramamide F = 446. Keramamide G = 447. Keramamide H = 448. Keramamide J = 449. Keramamide K = 450. Keramamide L = 477. Keramamide M = 406. Keramamide N = 407. Kipukasin H = 908. Kipukasin I = 909. Konbamide = 478. Konbanamide = 478. Kororamide = 451. Koshikamide A1 = 207. Koshikamide A2 = 256. Koshikamide B = 607. Koshikamide F = 608. Koshikamide H = 609. Kulokainalide 1 = 610. Kulokekahilide 1 = 611. Kulokekahilide 2 = 612. Kulolide 1 = 613. Kulolide 2 = 614.

435

436

Index 1 Compound Name and Synonym Index

Kulolide 3 = 615. Kulomoopunalide 1 = 616. Kulomoopunalide 2 = 617. Kumusine = 917. Kurahamide = 804. Kurahyne = 848. L Lagunamide A = 618. Lagunamide B = 619. Lagunamide C = 620. Largamide A = 621. Largamide B = 622. Largamide C = 623. Largamide D = 805. Largamide D oxazolidine = 806. Largamide E = 807. Largamide F = 808. Largamide G = 809. Largazole = 792. Lenthionine = 937. Leptosin A = 938. Leptosin B = 939. Leptosin C = 940. Leptosin D = 941. Leptosin E = 942. Leptosin F = 943. Leptosin G = 944. Leptosin G1 = 945. Leptosin G2 = 946. Leptosin H = 947. Leptosin I = 948. Leptosin J = 949. Leptosin K = 950. Leptosin K1 = 951. Leptosin K2 = 952. Leptosin M = 953. Leptosin M1 = 954. Leptosin N = 955. Leptosin N1 = 956. Leptosin O = 957. Leptosin P = 958. Leucamide A = 423. Lissoclibadin 1 = 959. Lissoclibadin 2 = 960. Lissoclibadin 4 = 961. Lissoclibadin 5 = 962. Lissoclibadin 6 = 963. Lissoclibadin 7 = 964.

Lissoclibadin 8 = 965. Lissoclibadin 9 = 966. Lissoclibadin 13 = 967. Lissoclibadin14 = 968. Lissoclinamide 2 = 424. Lissoclinamide 3 = 425. Lissoclin disulfoxide = 1017. lissoclinotoxin A = 969. lissoclinotoxin B = 970. Lissoclinotoxin D = 971. Lissoclinotoxin F = 972. Loihichelin A = 208. Loihichelin B = 209. Loihichelin C = 210. Loihichelin D = 211. Loihichelin E = 212. Loihichelin F = 213. Loloatin A = 323. Loloatin B = 324. Loloatin C = 325. Loloatin D = 326. Luteoalbusin A = 973. Luteoalbusin B = 974. Lyngbyabellin A = 793. Lyngbyabellin B = 794. Lyngbyabellin C = 795. Lyngbyabellin D = 796. Lyngbyabellin N = 856. Lyngbyastatin 1 = 624. Lyngbyastatin 10 = 800. Lyngbyastatin 2 = 625. Lyngbyastatin 4 = 810. Lyngbyastatin 5 = 811. Lyngbyastatin 6 = 812. Lyngbyastatin 7 = 626. Lyngbyastatin 8 = 813. M Mactanamide = 59. Majusculamide C = 627. Majusculamide D = 214. Malevamide D = 215. Malevamide E = 748. Marinovir = 296. Marthiapeptide A = 452. Massetolide A = 749. Massetolide B = 750. Massetolide C = 751. Massetolide D = 752.

Index 1 Compound Name and Synonym Index

Massetolide E = 753. Massetolide F = 754. Massetolide G = 755. Massetolide H = 756. 4ʹ-Methoxyasperphenamate = 864. 5-(Methoxymethyl)-4-[(methylsulfonyl)methyl]1,2,3-benzenetriol = 1018. 6-Methoxyspirotryprostatin B = 60. N-[14-Methyl-3-(13-methyl-4-tetradecenoyloxy) pentadecanoyl]glycine = 876. N-Methylated octapeptide RHM3 = 216. 3-Methylcytidine = 910. 3-Methyl-2ʹ-deoxycytidine = 911. N,N’-Methyleno-didemnin A = 628. 1-Methylisoguanosine = 907. N-Methylsansalvamide = 629. 5-(Methylthio)varacin A = 975. Microcin SF608 = 147. Microcionamide A = 327. Microcionamide B = 328. Microcolin A = 217. Microcolin B = 218. Microsclerodermin A = 329. Microsclerodermin B = 330. Microsclerodermin C = 331. Microsclerodermin D = 332. Microsclerodermin E = 333. Microsclerodermin F = 334. Microsclerodermin G = 335. Microsclerodermin H = 336. Microsclerodermin I = 337. Microspinosamide = 630. Microsporin A = 338. Microsporin B = 339. Microviridin A = 814. Microviridin B = 815. Microviridin C = 816. Microviridin D = 817. Microviridin E = 818. Milnamide B = 158. Mirabamide A = 631. Mirabamide B = 757. Mirabamide C = 758. Mirabamide D = 759. Mirabamide E = 632. Mirabamide F = 633. Mirabamide G = 634. Mirabamide H = 635. Miraziridine A = 219.

Miuraenamide A = 636. Mixirin A = 340. Mixirin B = 341. Mixirin C = 342. Mojavensin A = 849. Molassamide = 819. Mollamide A = 453. Mollemycin A = 850. Monamphilectine A = 837. Motuporin = 343. Mozukutoxin A = 1032. Mutremdamide A = 344. Mycalisine A = 912. N Nagahamide A = 637. Namenamicin = 976. Nazumamide A = 220. Neamphamide A = 638. Neamphamide B = 639. Neamphamide C = 640. Neamphamide D = 641. Neopetrosiamide A = 257. Neopetrosiamide B = 258. Neosiphoniamolide A = 642. Nereistoxin = 977. Nobilamide B = 221. Nodulapeptin A = 479. Nodulapeptin B = 480. Nodularin = 345. Nodularin 1 = 345. Nodularin 5 = 343. Norbisebromoamide = 222. Nordolastatin G = 643. Norlyngbyastatin 2 = 644. 57-Normajusculamide C = 645. Notoamide C = 61. Notoamide D = 62. O Obyanamide = 797. Okaramine S = 63. Onchidin = 646. Orbiculamide A = 346. Oriamide = 454. Oscillamide B = 481. Oscillamide C = 482. Oscillamide Y = 483. Oscillapeptin A = 820.

437

438

Index 1 Compound Name and Synonym Index

Oscillapeptin B = 821. Oscillapeptin C = 822. Oscillapeptin D = 823. Oscillapeptin E = 824. Oscillapeptin F = 825. Oscillapeptin J = 826. Oscillarin = 148. Otoamide C = 64. Ovothiol A = 865. Ovothiol B = 866. Ovothiol C = 867. 1-Oxo-1,2,4-trithiolane = 1019. 4-Oxo-1,2,4-trithiolane = 1020. 18-Oxotryprostatin A = 65. 13-Oxoverruculogen = 66. P Pahayokolide A = 347. Palauamide = 348. Palmyramide A = 647. Pandanamide B = 834. Papuamide A = 648. Papuamide A 4′′′-O-α-Lrhamnopyranoside = 759. Papuamide B = 649. Patellamide A = 426. Patellamide B = 427. Patellamide C = 428. Patellamide D = 429. Patellamide E = 430. Patellamide F = 431. Patellamide G = 432. Pedein A = 349. Pedein B = 350. Penicibrocazine B = 67. Penicibrocazine C = 68. Penicibrocazine D = 69. Penicibrocazine E = 70. Pentaporin A = 978. 1,2,3,5,6-Pentathiacycloheptane = 937. Peptidolipin B = 851. Peptidolipin D = 852. Perthamide B = 351. Perthamide C = 352. Perthamide D = 353. Perthamide E = 354. Perthamide F = 355. Perthamide G = 356. Perthamide H = 357.

Perthamide I = 358. Perthamide J = 359. Perthamide K = 408. Phakellistatin 1 = 360. Phakellistatin 2 = 361. Phakellistatin 3 = 362. Phakellistatin 4 = 363. Phakellistatin 5 = 364. Phakellistatin 6 = 365. Phakellistatin 7 = 366. Phakellistatin 8 = 367. Phakellistatin 9 = 368. Phakellistatin 10 = 369. Phakellistatin 11 = 370. Phakellistatin 14 = 1021. Phakellistatin 19 = 371. Phomazine B = 71. Phoriospongin A = 650. Phoriospongin B = 651. Piperazimycin A = 835. Piperazimycin B = 836. Pitipeptolide A = 652. Pitipeptolide B = 653. Pitipeptolide C = 654. Pitipeptolide D = 655. Pitipeptolide E = 656. Pitipeptolide F = 657. Pitiprolamide = 658. Plicatamide = 223. Plitidepsin = 490. Polycarpamine A = 979. Polycarpamine B = 980. Polycarpine = 981. Polydiscamide A = 659. Pompanopeptin A = 660. Porpoisamide A = 661. Porpoisamide B = 662. Prenylcyclotryprostatin B = 72. 13-O-Prenyl-26-hydroxyverruculogen = 73. Preulicyclamide = 455. Preulithiacyclamide = 456. [D-Pro4]Didemnin B = 663. 3-N-(1Z-Propenyl)-palythine = 871. Proximicin A = 121. Proximicin B = 122. Proximicin C = 123. Pseudoalterobactin A = 372. Pseudoalterobactin B = 373. Pseudotheonamide A1 = 224.

Index 1 Compound Name and Synonym Index

Pseudotheonamide A2 = 225. Pseudotheonamide B2 = 226. Pseudotheonamide C = 227. Pseudotheonamide D = 228. Pullularin A = 374. Pullularin C = 375. Pullularin F = 376. Purpuroine A = 877. Purpuroine B = 878. Purpuroine C = 879. Purpuroine D = 880. Purpuroine E = 881. Purpuroine F = 882. Purpuroine G = 883. Purpuroine H = 884. Purpuroine I = 885. Purpuroine J = 886. Pygmeine = 868. R Ramalin = 868. 9-β-D-Ribofuranosyl-9H-purin6-amin = 904. Rodriguesine A = 74. Rodriguesine B = 75. (cis)-Rolloamide A = 377. (trans)-Rolloamide A = 378. Roseocardin = 485. Roseotoxin B = 486. Rostratin A = 982. Rostratin B = 983. Rostratin C = 984. Rostratin D = 985. Rubrumazine A = 76. Rubrumazine B = 77. Rubrumazine C = 78. Rubrumline A = 79. Rubrumline B = 80. Rubrumline C = 81. Rubrumline D = 82. Rubrumline E = 83. Rubrumline F = 84. Rubrumline G = 85. Rubrumline H = 86. Rubrumline I = 87. Rubrumline J = 88. Rubrumline K = 89. Rubrumline L = 90. Rubrumline M = 91.

Rubrumline N = 92. Rubrumline O = 93. S Salinamide A = 827. Salinamide B = 828. Salinamide C = 664. Salinamide D = 665. Salinamide E = 666. Sansalvamide = 667. Sansalvamide A = 667. Sarcotride A = 897. Scleritodermin A = 457. Sclerotide A = 379. Sclerotide B = 380. Scopularide A = 668. Scopularide B = 669. Scytalidamide A = 381. Scytalidamide B = 382. Seragamide A = 670. Seragamide B = 671. Seragamide C = 672. Seragamide D = 673. Seragamide E = 674. Shimofuridin A = 913. Shishijimicin A = 986. Shishijimicin B = 987. Shishijimicin C = 988. Shornephine A = 94. O-Sialic acid = 893. Solomonamide A = 675. Solonamide A = 383. Solonamide B = 384. Somamide A = 829. Somamide B = 830. Spicellamide A = 564. Spicellamide B = 563. Spiroidesin = 167. Spirotryprostatin A = 95. Spirotryprostatin B = 96. Spirotryprostatin C = 97. Spirotryprostatin D = 98. Spirotryprostatin E = 99. Spirotryprostatin F = 100. Spongosine = 914. Stellatolide A = 760. Stellatolide B = 761. Stellatolide C = 762. Stellatolide D = 763.

439

440

Index 1 Compound Name and Synonym Index

Stellatolide E = 764. Stellatolide F = 765. Stellatolide G = 766. Stylissamide X = 385. Stylissatin A = 386. Stylopeptide 1 = 387. Stylostatin 1 = 388. Sulfinyltheonellapeptolide = 676. 12ʹ-Sulfoxythiocoraline = 677. Sungsanpin = 769. Symplocamide A = 678. Symplocin A = 229. Symplostatin 1 = 230. Symplostatin 3 = 231. T Tamandarin A = 679. Tamandarin B = 680. Tanjungide A = 989. Tanjungide B = 990. Tasiamide A = 232. Tasiamide B = 233. Tasipeptin A = 831. Tasipeptin B = 832. Tauramamide = 234. Tausalarin C = 681. Tawicyclamide A = 458. Tawicyclamide B = 459. Terezine D = 101. Terpeptin = 124. Terpeptin A = 168. Terpeptin B = 169. 8,9,10,11-Tetrahydro-6-methoxy-1,2,3,4, 5-pentathiepino[6,7-f]isoquinolin7-ol = 970. Tetrahydroveraguamide A = 682. 1,2,4,6-Tetrathiepane = 991. Thalassospiramide A = 767. Theonegramide = 389. Theonellamide A = 390. Theonellamide B = 391. Theonellamide C = 392. Theonellamide D = 393. Theonellamide E = 394. Theonellapeptolide Ia = 683. Theonellapeptolide Ib = 684. Theonellapeptolide Ic = 685. Theonellapeptolide Id = 686. Theonellapeptolide Ie = 687.

Theonellapeptolide If = 688. Theonellapeptolide IId = 689. Theonellapeptolide IIIe = 395. Theopalauamide = 396. Theopapuamide A = 690. Theopapuamide B = 691. Theopapuamide C = 692. Thiaplakortone A = 1022. Thiaplakortone B = 1023. Thiaplakortone C = 1024. Thiaplakortone D = 1025. Thiaplidiaquinone A = 1026. Thiaplidiaquinone B = 1027. Thiochondrilline C = 235. Thiocoraline = 693. Thiolsulfonate = 1028. Thiomarinol A = 992. Thiomarinol B = 1029. Thiomarinol C = 993. Thiomarinol D = 994. Thiomarinol F = 995. Thymidine-5ʹ-carboxylic acid = 915. Tiglicamide A = 694. Tiglicamide B = 695. Tiglicamide C = 696. Tokaramide A = 170. Tortugamide = 794. Toyocamycin = 916. TP-1161 = 798. Trachycladine A = 917. Trichoderide = 397. Trichoderin A = 236. Trichoderin A1 = 237. Trichoderin B = 238. 1,2,4-Trithiolane = 996. Trunkamide A = 460. Tryprostatin A = 102. Tryprostatin B = 103. Tumescenamide A = 398. Tumonoic acid A = 887. Tumonoic acid F = 888. Tumonoic acid I = 889. Tunichrome An1 = 125. Tunichrome Mm 1 = 126. Tunichrome Mm 2 = 127. Turnagainolide B = 399. U Ulicyclamide = 461. Ulithiacyclamide = 433.

Index 1 Compound Name and Synonym Index

Ulithiacyclamide B = 434. Ulithiacyclamide E = 462. Ulithiacyclamide F = 435. Ulithiacyclamide G = 436. Ulongapeptin = 697. Unguisin A = 400. Unguisin B = 401. Unnarmicin A = 698. Unnarmicin C = 699. Usujirene = 871. V Varacin = 997. Varacin A = 998. Varacin B = 999. Varacin C = 1000. Variecolorin A = 104. Variecolorin B = 105. Variecolorin C = 106. Variecolorin D = 107. Variecolorin E = 108. Variecolorin F = 109. Variecolorin G = 110. Variecolorin H = 111. Variecolorin I = 112. Variecolorin J = 113. Variecolorin K = 114. Variecolorin M = 115. Variecolorin N = 116. Variecolorin O = 117. Venturamide A = 437. Venturamide B = 438.

Veraguamide A = 700. Veraguamide B = 701. Veraguamide C = 702. Veraguamide D = 703. Veraguamide E = 704. Veraguamide F = 705. Veraguamide G = 706. Verruculogen = 118. Versicamide H = 119. Verticillin A = 1001. Verticillin D = 1002. Viequeamide A = 707. Virenamide B = 128. Viridamide A = 853. Viridamide B = 854. Viscosin = 768. Vitilevuamide = 833. W Wainunuamide = 402. Wewakamide A = 708. Wewakpeptin A = 709. Wewakpeptin B = 710. Wewakpeptin C = 711. Wewakpeptin D = 712. Y Yanucamide A = 713. Yanucamide B = 714. Z Zygosporamide = 715.

441

Index 2 Compound Molecular Formula Index The Molecular Formula Index of Volume 8 lists the molecular formulae of all 1,032 active isolated compounds from marine organisms given in the HAMNP Volume 8 in Hill convention order. Under a bold formula, all related compound names following code numbers are listed in the code number order too. C2 C2H4OS3 – 1-Oxo-1,2,4-trithiolane, 1019. – 4-Oxo-1,2,4-trithiolane, 1020. C2H4S3 – 1,2,4-Trithiolane, 996. C2H4S5 – Lenthionine, 937. C3 C3H6O2S4 – Thiolsulfonate, 1028. C3H6S4 – 1,2,4,6-Tetrathiepane, 991. C4 C4H10O3 – Mozukutoxin A, 1032. C5 C5H11AsO2 – Arsenobetaine, 1030. C5H11NS2 – Nereistoxin, 977. C5H12N2O2 – (S)-2,5-Diaminopentanoic acid, 857. C6 C6H10O3S – 4-(Ethenylsulfonyl)-2-butanone, 1011. C6H12N4O2 – Carnosadine, 860. C6H13NO5 – 3-Amino-3-deoxy-D-glucose, 892. C7 C7H11N3O2S – Ovothiol A, 865. C7H13NO3 – Betonicine, 859.

C8 C8H9N5O3 – Erinacean, 870. C8H13N3O2S – Ovothiol B, 866. C8H17NO3 – Echinobetaine A, 869. C9 C9H11NO2S5 – lissoclinotoxin A, 969. C9H15N3O2S – Ovothiol C, 867. C9H18O8 – Floridoside, 900. C10 C10H11NO2S5 – lissoclinotoxin B, 970. C10H12N2O6 – Thymidine-5ʹ-carboxylic acid, 915. C10H13NO2S3 – Varacin A, 998. C10H13NO2S5 – Varacin, 997. C10H13NO3S3 – Varacin B, 999. – Varacin C, 1000. C10H13N5O3 – 2ʹ-Deoxyadenosine, 905. C10H13N5O4 – Adenosine, 904. C10H14O6S – 5-(Methoxymethyl)-4-[(methylsulfonyl) methyl]-1,2,3-benzenetriol, 1018. C10H15NO4 – α-Allokainic acid, 858. – (–)-Kainic acid, 863. C10H15N3O4 – 3-Methyl-2ʹ-deoxycytidine, 911.

Index 2 Compound Molecular Formula Index

C10H15N3O5 – 3-Methylcytidine, 910. C10H16N2O2 – (3S,8αS)-Cyclo(prolylvalyl), 31. C10H17N3O2 – Bacillusamide A, 6. C11 C11H13IN4O3 – 5ʹ-Deoxy-5-iodotubercidin, 906. C11H14ClN5O3 – Trachycladine A, 917. C11H15NO2S4 – 5-(Methylthio)varacin A, 975. C11H15NO2S5 – Lissoclibadin14, 968. C11H15N3O4 – Pygmeine, 868. C11H15N5O5 – Doridosine, 907. – Spongosine, 914. C11H18N2O2 – Cyclo(L-Ile-L-Pro), 29. – Cyclo(leucylprolyl), 30. C11H18N2O3 – Cyclo(2-hydroxy-Pro-R-Leu), 24. – Cyclo-(4-S-hydroxy-R-proline-R-isoleucine), 25. – (3S,7R,8aS)-Cyclo(4-hydroxyprolylleucyl), 26. C11H19NO9 – N-Acetylneuraminic acid, 893. C12 C12H6N2O6S – Ascidiathiazone B, 1007. C12H8N2O6S – Ascidiathiazone A, 1006. C12H11BrN2OS3 – Euthyroideone B, 1015. – Euthyroideone C, 1016. C12H11N3O4S – Thiaplakortone A, 1022. C12H11N3O6 – Proximicin A, 121. C12H12Br2N2O2 – 5,6-Dibromoabrine, 861. C12H13BrN2O3S – Euthyroideone A, 1014. C12H13N3O4S – Thiaplakortone B, 1023.

443

C12H13N5O4 – Toyocamycin, 916. C13 C13H12N2O3S2 – 6-Deoxy-5a,6-didehydrogliotoxin, 927. C13H12N2O4S2 – 5a,6-Didehydrogliotoxin, 929. C13H13N5O3 – Mycalisine A, 912. C13H14N2O3S3 – (+)-5-Hydroxy-4-(4-hydroxy-3-methoxyphenyl)4-(2-imidazolyl)-1,2,3-trithiane, 935. – (–)-5-Hydroxy-4-(4-hydroxy-3-methoxyphenyl)4-(2-imidazolyl)-1,2,3-trithiane, 936. C13H14N2O4S2 – Gliotoxin, 932. – Gliotoxin, 933. C13H14N2O4S4 – Gliotoxin G, 934. C13H16BrCl2NO3 – Purpuroine C, 879. C13H16Br2ClNO3 – Purpuroine E, 881. C13H16Br2INO3 – Purpuroine D, 880. C13H16Br3NO3 – Purpuroine A, 877. C13H17Br2NO3 – Purpuroine B, 878. C13H19NO2S3 – Lissoclibadin 13, 967. C13H19NO2S4 – 6-(2-Aminoethyl)-3,4dimethoxybenzotrithiane, 918. C13H19NO2S6 – N,N-Dimethyl-5-(methylthio)varacin, 931. C13H20N2O5 – 3-N-(1Z-Propenyl)-palythine, 871. C14 C14H13N3O6S – Thiaplakortone C, 1024. – Thiaplakortone D, 1025. C14H14N2O2S – 1-Ethyl-4-methylsulfone-βcarboline, 1012. C14H16BrN3O2S – Eudistomin K sulphoxide, 1013.

444

Index 2 Compound Molecular Formula Index

C14H16N2O2 – Cyclo(D-Pro-D-Phe), 32. C14H16N2O3 – Cyclo-(D-cis-Hyp-L-Phe), 28. – Cyclo(D-Tyr-D-Pro), 33. C14H16N2O3S – Bis(dethio)-10a-methylthio-3a-deoxy3,3a-didehydrogliotoxin, 11. C14H19BrINO3 – Purpuroine I, 885. C14H19I2NO3 – Purpuroine G, 883. C14H19NO3S3 – Polycarpamine B, 980. C14H20Cl6N2O2 – Dysamide A, 46.

C17 C17H10Br2N2O4S – Echinosulfone A, 1010. C17H19BrN6O2 – Barettin, 7. C17H21BrN6O2 – 8,9-Dihydrobarettin, 38. C17H25N5O7 – Benarthin, 120. C17H35N5O5 – Istamycin A, 898. – Istamycin B, 899.

C15 C15H18N2O3S – (R,Z)-3-Benzylidene-6-(hydroxymethyl)1,4-dimethyl-6-(methylthio)2,5- piperazinedione, 8. C15H18N2O4S2 – Bis(dethio)bis-(methylthio)5a,6-didehydro- gliotoxin, 9. C15H20BrN2O21+ – Purpuroine J, 886. C15H20N2O3S2 – Deoxybisdethiobis(methylthio) gliotoxin, 35. C15H20N2O4S2 – Bisdethiobis(methylthio)gliotoxin, 10. C15H21BrINO3 – Purpuroine H, 884. C15H21I2NO3 – Purpuroine F, 882. C15H23NO3S3 – Polycarpamine A, 979.

C18 C18H18N2O6S2 – Brocazine B, 922. – Brocazine F, 924. C18H19NO4S – Conicaquinone A, 1008. – Conicaquinone B, 1009. C18H20N2O6S2 – Brocazine E, 923. – Rostratin B, 983. C18H20N2O6S4 – Rostratin D, 985. C18H20N2O9 – Kipukasin H, 908. – Kipukasin I, 909. C18H22N2O4S4 – Lissoclinotoxin D, 971. C18H24N2O3S2 – Antibiotic Sch 54796, 2. C18H24N2O6S2 – Rostratin A, 982. C18H27NO10 – Astebatherioside C, 902. C18H33N3O2S – (R)-Agelasidine A, 1005.

C16 C16H16Br2N4O2S2 – Tanjungide A, 989. – Tanjungide B, 990. C16H17N3O2 – Brevianamide F, 12. C16H17N3O3 – Cyclo(4-hydroxy-S-Pro-S-Trp), 27. C16H22N4O2 – Aurantiamine, 4.

C19 C19H19N3O6 – Tunichrome Mm 1, 126. C19H20N2O4 – Mactanamide, 59. C19H20N2O7S2 – Brocazine A, 921. C19H21N3O2 – Chrysogenazine, 17. – Dihydroneochinulin B, 41.

Index 2 Compound Molecular Formula Index

445

C19H21N3O3 – Cristatumin A, 18. – Variecolorin O, 117. C19H21N3O4 – Golmaenone, 51. C19H22N2O5S – Penicibrocazine B, 67. C19H23N3O2 – Rubrumline O, 93. – Terezine D, 101. C19H23N3O3 – 14-Hydroxyterezine D, 56. – Rubrumline J, 88. – Rubrumline M, 91. C19H33NO4 – Tumonoic acid A, 887. C19H33N3O5 – Janolusimide, 162.

C21H24N6O4S2 – Venturamide A, 437. C21H25N3O2 – Tryprostatin B, 103. C21H27N3O2 – (Indole-N-isoprenyl)-tryptophanvaline, 57. C21H27N3O3 – Rubrumline N, 92. C21H29NO6 – N-[[3,4-Dihydro-3S-hydroxy-2S-methyl2-(4′R-methyl-3′S-pentenyl)-2H-1benzopyran-6- yl]carbonyl]-threonine, 862. C21H29N5O9 – Solomonamide A, 675. C21H37NO4 – Ethyl tumonoate A, 875. C21H37NO5 – Tumonoic acid F, 888.

C20 C20H19N3O7 – Proximicin B, 122. C20H20Br2N4S2 – Bis(6-bromo-2-tryptaminyl) disulfide, 920. C20H22N2O3S2 – Phomazine B, 71. C20H23N3O3 – Variecolorin H, 111. C20H23N3O4 – (+)-Azonazine, 5. – Rubrumline K, 89. C20H24N2O6S2 – Penicibrocazine E, 70. C20H24N2O8S2 – Rostratin C, 984. C20H26N2O6S2 – Penicibrocazine C, 68. – Penicibrocazine D, 69. C20H32N4O4 – (all-L)-Cyclo(Pro-Val)2, 297.

C22 C22H17NO6S – (+)-Adociaquinone A, 1003. – (+)-Adociaquinone B, 1004. C22H20N4O6 – Proximicin C, 123. C22H23N3O4 – 6-Methoxyspirotryprostatin B, 60. C22H24N2O7S2 – Alternarosin A, 1. C22H24N2O10 – Aspergillusol A, 873. C22H24N6O2S2 – Polycarpine, 981. C22H25N3O4 – 9-Hydroxyfumitremorgin C, 54. – 18-Oxotryprostatin A, 65. – Spirotryprostatin A, 95. C22H25N3O5 – 12,13-Dihydroxyfumitremorgin C, 42. – 9-Hydroxyfumitremorgin C, 55. C22H25N3O6 – 8,9-Dihydroxyisospirotryprostatin A, 43. – Spirotryprostatin F, 100. C22H26N6O5S2 – Venturamide B, 438. C22H27N3O3 – Tryprostatin A, 102. C22H28N2O3 – Deoxymycelianamide, 36.

C21 C21H21N3O2 – Brevianamide K, 13. C21H21N3O3 – Spirotryprostatin B, 96. C21H23N3O2 – Brevianamide W, 15.

446

Index 2 Compound Molecular Formula Index

C22H28N2O4 – Gliocladride A, 49. – Gliocladride B, 50. C22H30N2O3 – Gliocladride, 48. C22H30N2O4S3 – Lissoclibadin 4, 961. C22H30N2O4S4 – Lissoclibadin 7, 964. C22H35N5O7 – Trichoderide, 397. C22H36N4O4 – Cyclo(isoleucylprolylleucylprolyl), 295. C23 C23H20N4O3S2 – Luteoalbusin A, 973. C23H20N4O3S3 – Luteoalbusin B, 974. C23H25N3O3 – Variecolorin J, 113. C23H27N3O5 – Rubrumline L, 90. C23H27N3O6 – Tunichrome Mm 2, 127. C23H36N4O4 – Aspochracin, 267. C23H36N6O5 – Tokaramide A, 170. C24 C24H23Br2N7O5 – Bromobenzisoxazolone barettin, 16. C24H29Cl2N3O2 – Variecolorin B, 105. C24H29N3O2 – Variecolorin G, 110. C24H29N3O3 – Variecolorin C, 106. – Variecolorin E, 108. – Variecolorin M, 115. C24H29N3O4 – Rubrumline D, 82. – Variecolorin N, 116. C24H30ClN3O3 – Variecolorin A, 104. – Variecolorin F, 109. C24H30Cl2N2O8S2 – Lyngbyabellin C, 795.

C24H31N3O4 – Rubrumazine B, 77. – Rubrumline A, 79. – Rubrumline H, 86. C24H32N6O5S – Dolastatin I, 422. C24H33N3O4 – Rubrumazine C, 78. C24H34N2O4S3 – Lissoclibadin 6, 963. C24H34N2O4S4 – Lissoclibadin 5, 962.

C25 C25H24N4O3S2 – Leptosin D, 941. C25H24N4O3S3 – Leptosin E, 942. C25H24N4O3S4 – Leptosin F, 943. C25H26N2O5 – Shornephine A, 94. C25H31N3O3 – Variecolorin I, 112. C25H31N3O4 – Rubrumline E, 83. C25H31N5O7S3 – Thiochondrilline C, 235. C25H32Cl2N2O8S2 – Deacetylhectochlorin, 779. C25H32N6O4S2 – Bistratamide H, 416. C25H32N6O5S – Bistratamide G, 415. C25H33N3O4 – Rubrumazine A, 76. – Rubrumline B, 80. – Rubrumline I, 87. C25H34N3O8P – Antibiotic K 26, 149. C25H34N6O4S2 – Bistratamide E, 413. C25H34N6O5S – Bistratamide D, 412. C25H35N3O4 – Rubrumline F, 84. C25H36N6O5S – Bistratamide F, 414.

Index 2 Compound Molecular Formula Index

C25H36N6O6S – Bistratamide I, 417. C25H42N6O10S – Dysinosin C, 145. C25H42N6O7 – Dysinosin D, 146. C25H45N3O6S – Carmaphycin A, 151. C25H45N3O7S – Carmaphycin B, 152. C25H46N2O7 – Gageotetrin A, 841. C25H50O7 – Sarcotride A, 897. C26 C26H25N3O11 – Tunichrome An1, 125. C26H31N3O3 – Dihydrocarneamide A, 39. C26H31N3O4 – Notoamide C, 61. – Notoamide D, 62. – Otoamide C, 64. C26H32N4O5 – Asperterrestide A, 266. C26H33N3O5 – Rubrumline C, 81. C26H35N3O5 – Rubrumline G, 85. C26H36N4O8 – Aspergillipeptide C, 265. C26H38N2O4S5 – Lissoclibadin 2, 960. – Lissoclinotoxin F, 972. C26H38N2O6S4 – Lissoclin disulfoxide, 1017. C26H39N3O2 – Monamphilectine A, 837. C26H40N2O5 – Haliclamide, 566. C26H42N4O3 – Rodriguesine A, 74. C26H42N4O4 – Etzionin, 47. C26H43ClN6O10S – Chlorodysinosin A, 142. C26H44N6O10S – Dysinosin A, 143.

447

C27 C27H31N3O7 – 13-Oxoverruculogen, 66. C27H32N6O4S2 – Bistratamide B, 411. C27H33N3O3 – 9ξ-O-2(2,3-Dimethylbut-3-enyl)brevianamide Q, 45. C27H33N3O6 – 2′ξ-Hydroxy-fumitremorgin B Δ3′-Isomer (1), 52. – 2′ξ-Hydroxy-fumitremorgin B Δ3′-Isomer (2), 53. – Spirotryprostatin C, 97. C27H33N3O7 – Spirotryprostatin D, 98. – Verruculogen, 118. C27H33N3O8 – Spirotryprostatin E, 99. C27H34Cl2N2O9S2 – Hectochlorin, 789. C27H34N6O4S2 – Bistratamide A, 410. C27H35N3O4 – Variecolorin D, 107. – Variecolorin K, 114. C27H38BrN3O6 – Geodiamolide E, 559. C27H38ClN3O6 – Geodiamolide F, 560. C27H38IN3O6 – Geodiamolide D, 558. C27H38N4O6 – Azumamide E, 276. C27H39BrN4O4 – (–)-Jasplakinolide Z4, 166. C27H39N5O5 – Azumamide A, 275. C27H41IN2O6 – Doliculide, 550. C27H44N4O3 – Rodriguesine B, 75. C27H47NO7 – Tumonoic acid I, 889. C27H49N5O7 – Fellutamide B, 155. C27H49N5O8 – Fellutamide A, 154. C27H51N5O7 – Fellutamide C, 156.

448

Index 2 Compound Molecular Formula Index

C28 C28H29N3O4 – Versicamide H, 119. C28H30N4O6S2 – Antibiotic B 90063, 919. C28H33N3O3 – 12-Demethyl-12-oxoeurotechinulin B, 34. C28H34N4O3 – Aspergillamide A (1998), 872. C28H35N3O5 – Prenylcyclotryprostatin B, 72. C28H38IN3O7 – Geodiamolide G, 561. C28H40BrN3O6 – Geodiamolide B, 556. C28H40ClN3O6 – Geodiamolide C, 557. C28H40Cl2N4O7S2 – Lyngbyabellin B, 794. C28H40IN3O6 – Geodiamolide A, 555. C28H40IN3O7 – Seragamide D, 673. C28H40N4O3 – Terpeptin, 124. C28H40N4O4 – Terpeptin A, 168. – Terpeptin B, 169. C28H40N4O5 – Microsporin A, 338. C28H42N4O4 – Hemiasterlin B, 160. C28H42N4O5 – Microsporin B, 339. C28H43N7O8 – Nazumamide A, 220. C28H45N3O5 – Antillatoxin, 716. C28H53N5O8 – Fellutamide F, 157. C29 C29H36N6O6 – Pseudotheonamide D, 228. C29H37N3O2 – Didehydroechinulin B, 37. C29H37N3O3 – Cristatumin B, 19.

C29H37N7O6S – Leucamide A, 423. C29H38BrClN9O8 – Cyclocinamide A, 294. C29H40Cl2N4O7S2 – Lyngbyabellin A, 793. C29H40N8O6S2 – Dolastatin 3, 443. C29H42BrN3O7 – Seragamide B, 671. C29H42ClN3O7 – Seragamide C, 672. C29H42IN3O6 – Neosiphoniamolide A, 642. C29H42IN3O7 – Seragamide A, 670. C29H42IN3O8 – Seragamide E, 674. C29H42N4O5S3 – Largazole, 792. C29H44Cl2N6O6 – Aeruginosin KY642, 141. C29H44Cl2N6O9S – Aeruginosin 101, 129. C29H44N4O4 – Hemiasterlin A, 159. – Hemiasterlin C, 161. C29H45BrN6O9S – Aeruginosin 98C, 139. C29H45ClN6O6 – Aeruginosin KY608, 140. C29H45ClN6O9S – Aeruginosin 98A, 137. C29H46N6O9S – Aeruginosin 98B, 138. C29H48ClN5O8 – Destruxin E chlorohydrin, 484. C29H51NO12 – Eodoglucomide B, 891. C30 C30H28N6O4S4 – 11,11ʹ-Dideoxyverticillin A, 930. C30H28N6O5S4 – 11-Deoxyverticillin A, 928. C30H28N6O6S4 – Verticillin A, 1001. C30H31N7O3S4 – Marthiapeptide A, 452.

Index 2 Compound Molecular Formula Index

C30H38N4O2S – Virenamide B, 128. C30H41N5O6S – Obyanamide, 797. C30H42N8O6S2 – Homodolastatin 3, 444. C30H44NO11S2 – Thiomarinol B, 1029. C30H44N2O8S2 – Thiomarinol C, 993. C30H44N2O9S2 – Thiomarinol A, 992. C30H44N4O6 – Turnagainolide B, 399. C30H45ClN6O10S – Aeruginosin 89B, 136. C30H45N5O8 – Depsipeptide 1962A, 534. C30H46N4O4 – Hemiasterlin, 158. C30H46O19 – Astebatherioside D, 903. C30H48N6O6S – Keenamide A, 445. C30H48N6O7 – Aeruginosin 298A, 135. C30H49N5O7 – Roseotoxin B, 486. C30H52N8O9 – Miraziridine A, 219. C30H53NO12 – Eodoglucomide A, 890. C31 C31H43N3O2 – Cristatumin F, 20. C31H44N2O9S2 – Thiomarinol F, 995. C31H46N2O9S2 – Thiomarinol D, 994. C31H46N4O8 – Guangomide B, 564. C31H46N4O9 – Guangomide A, 563. C31H46N6O9 – Pandanamide B, 834. C31H47ClN8O9 – Piperazimycin B, 836.

C31H47ClN8O10 – Piperazimycin A, 835. C31H47N3O7 – Dolastatin D, 548. C31H48N4O5 – Solonamide A, 383. C31H52N6O15S – Dysinosin B, 144. C31H53N5O7 – Roseocardin, 485. C31H54N4O7S – Halipeptin A, 788. C31H55N5O7 – Emericellamide A, 551. C31H58N8O11 – Callipeltin J, 187. C32 C32H26O12 – Kelletinin I, 894. C32H32N6O4 – Aspergilazine A, 3. C32H32N6O7S4 – Leptosin C, 940. – Leptosin I, 948. – Leptosin J, 949. C32H32N6O7S5 – Leptosin B, 939. – Leptosin G2, 946. C32H32N6O7S6 – Leptosin A, 938. – Leptosin G1, 945. – Leptosin H, 947. C32H32N6O7S7 – Leptosin G, 944. C32H32N6O8S4 – Verticillin D, 1002. C32H36N4O3 – Okaramine S, 63. C32H41N3O8 – 13-O-Prenyl-26hydroxyverruculogen, 73. C32H42N8O6S4 – Ulithiacyclamide, 433. C32H44N6O6 – Microcin SF608, 147. C32H46N8O8S4 – Preulithiacyclamide, 456.

449

450

Index 2 Compound Molecular Formula Index

C32H50N4O6 – Sansalvamide A, 667. C32H57N5O7 – Emericellamide B, 552. C32H57N5O7S – Arenamide C, 720. C33 C33H30O12 – Kelletinin II, 896. C33H32N2O5 – 4ʹ-Methoxyasperphenamate, 864. C33H36N6O7S2 – Leptosin O, 957. – Leptosin P, 958. C33H36N6O8S2 – Leptosin M1, 954. C33H36N6O8S3 – Leptosin N1, 956. C33H36N6O8S4 – Leptosin M, 953. – Leptosin N, 955. C33H39ClN2O8 – Cryptophycin 176, 509. C33H40N4O6 – Alternaramide, 487. C33H39N7O5S2 – Ulicyclamide, 461. C33H41N7O5S2 – Lissoclinamide 2, 424. – Lissoclinamide 3, 425. C33H41N7O6S2 – Preulicyclamide, 455. C33H44N6O11S – Aeruginosin 102A, 130. – Aeruginosin 102B, 131. C33H45N3O3 – Indotertine B, 58. C33H47N3O5 – Antillatoxin B, 717. C33H47N3O7 – Yanucamide A, 713. C33H47N9O8 – Cyclotheonamide D, 301. C33H50N4O6 – Porpoisamide A, 661. – Porpoisamide B, 662. C33H52N4O5 – Solonamide B, 384.

C33H52N4O6 – N-Methylsansalvamide, 629. C33H57N3O9 – Enniatin B, 463. C33H61NO5 – N-[14-Methyl-3-(13-methyl-4-tetradecenoyloxy) pentadecanoyl]glycine, 876. C34 C34H36N6O6S4 – Leptosin K, 950. C34H36N6O6S5 – Leptosin K1, 951. C34H36N6O6S6 – Leptosin K2, 952. C34H39N5O4 – Diketopiperazine dimer, 44. C34H40Cl2N2O7 – Cryptophycin 45, 525. C34H40Cl2N2O8 – Cryptophycin 23, 514. C34H41ClN2O7 – Cryptophycin 17, 507. – Cryptophycin 19, 511. – Cryptophycin 28, 517. – Cryptophycin 29, 518. – Cryptophycin 49, 527. C34H41ClN2O8 – Cryptophycin 16, 506. – Cryptophycin 21, 513. – Cryptophycin 40, 523. – Cryptophycin 50, 528. C34H41NO6S – Thiaplidiaquinone A, 1026. – Thiaplidiaquinone B, 1027. C34H42BrN3O7 – Miuraenamide A, 636. C34H42N2O7 – Cryptophycin 43, 524. C34H42N2O8 – Cryptophycin 24, 515. C34H43N7O5S2 – Cyclodidemnamide, 421. C34H44IN3O7 – Geodiamolide H, 562. C34H44N4O12 – Shimofuridin A, 913. C34H44N6O5 – Oscillarin, 148.

Index 2 Compound Molecular Formula Index

C34H48N6O6S – Comoramide A, 420. C34H48N10O13 – Dibenarthin, 153. C34H49N3O7 – Yanucamide B, 714. C34H50N6O7S – Comoramide B, 441. C34H53ClN6O12S – Aeruginosin 205A, 133. – Aeruginosin 205B, 134. C34H53NO22 – Astebatherioside B, 901. C34H53N5O7 – Scopularide B, 669. – Arenamide B, 719. C34H59N3O9 – Enniatin D, 464. C35 C35H40N8O6S4 – Ulithiacyclamide B, 434. C35H42Cl2N2O7 – Cryptophycin 175, 508. C35H42Cl2N2O8 – Cryptophycin 31, 521. C35H42N8O7S4 – Ulithiacyclamide F, 435. – Ulithiacyclamide G, 436. C35H43BrN4O6 – Jasplakinolide F, 584. – Jasplakinolide H, 586. – Jasplakinolide J, 587. – Jasplakinolide M, 590. C35H43ClN2O7 – Cryptophycin 18, 510. – Cryptophycin 3, 519. – Cryptophycin 46, 526. C35H43ClN2O8 – Cryptophycin 1, 505. – Cryptophycin 54, 530. C35H43N3O7 – Spiroidesin, 167. C35H44N2O7 – Cryptophycin 4, 522. C35H44N2O8 – Cryptophycin 2, 512. C35H44N8O8S4 – Ulithiacyclamide E, 462.

C35H45ClN2O8 – Cryptophycin 26, 516. – Cryptophycin 30, 520. C35H46N4O7 – Jasplakinolide O, 592. C35H47N5O7 – Cotteslosin B, 292. C35H48N4O5 – Belamide A, 150. C35H48N6O8 – Aeruginosin 103A, 132. C35H49N3O6S6 – Lissoclibadin 9, 966. C35H50N8O6S2 – Patellamide A, 426. C35H52N8O8S – Phakellistatin 5, 364. C35H53N5O7 – Desmethylisaridin C1, 536. C35H53N5O8 – Desmethylisaridin G, 537. C35H56N8O5 – Criamide A, 192. C35H57N5O6 – Dolastatin C, 874. C35H63N5O9 – Kailuin A, 743. C36 C36H20Br2N6O4S2 – (R,R)-16,17-Dehydrodiscorhabdin W, 925. – (S,S)-16,17-Dehydrodiscorhabdin W, 926. C36H43BrN4O7 – Jasplakinolide B, 580. – Jasplakinolide G, 585. – (+)-Jasplakinolide W, 600. C36H43N9O8 – Cyclotheonamide C, 300. C36H44Br2N4O6 – (–)-Jasplakinolide R, 596. – (+)-Jasplakinolide R1, 597. C36H45BrN4O6 – Jasplakinolide, 579. C36H45BrN4O7 – Jasplakinolide C, 581. – Jasplakinolide E, 583. – Jasplakinolide K, 588. – Jasplakinolide L, 589. – Jasplakinolide N, 591. – (+)-Jasplakinolide V, 599.

451

452

Index 2 Compound Molecular Formula Index

C36H45ClN2O8 – Cryptophycin 52, 529. C36H45N9O8 – Pseudotheonamide A1, 224. – Pseudotheonamide A2, 225. – Pseudotheonamide C, 227. – Cyclotheonamide A, 298. C36H46N4O6 – Jasplakinolide Q, 595. – Jasplakinolide S, 598. C36H46N4O7 – Chondramide A, 503. C36H47BrN4O7 – (+)-Jasplakinolide Z1, 163. C36H47N9O8 – Dihydrocyclotheonamide A, 305. C36H50N4O6 – Unnarmicin A, 698. – Zygosporamide, 715. C36H52N8O5S3 – Tawicyclamide B, 459. C36H52N8O6S2 – Ascidiacyclamide, 409. C36H53N3O9 – Palmyramide A, 647. C36H53N7O10S – Phakellistatin 14, 1021. C36H53N11O18 – Alterobactin A, 488. C36H54N8O9 – Stylostatin 1, 388. C36H55N5O8 – Isaridin G, 576. C36H55N11O19 – Alterobactin B, 175. C36H57BrN4O8 – Veraguamide B, 701. C36H57FeN6O6 – Ferrineoaspergillin, 1031. C36H57N5O7 – Scopularide A, 668. – Arenamide A, 718. C36H58N8O5 – Criamide B, 193. C36H59N7O10 – Gymnangiamide, 201. C36H65N7O13 – Amphibactin T, 178.

C37 C37H39N7O8 – Sclerotide A, 379. – Sclerotide B, 380. C37H45N9O8 – Pseudotheonamide B2, 226. C37H46N8O6S2 – Patellamide C, 428. – Patellamide F, 431. C37H47BrN4O6 – Jasplakinolide D, 582. C37H47N9O8 – Cyclotheonamide B, 299. C37H48N4O9 – Jasplakinolide P, 593. – 21-epi-Jasplakinolide P, 594. C37H49BrN4O7 – (+)-Jasplakinolide Z2, 164. C37H51N5O6 – Dragomabin, 198. C37H56N8O7 – Unguisin B, 401. C37H57N5O5 – Dragonamide E, 200. C37H57N5O8 – Tumescenamide A, 398. C37H59BrN4O8 – Veraguamide A, 700. C37H59N5O5 – Dragonamide A, 199. C37H60N4O8 – Veraguamide C, 702. C37H61N7O13 – Celebeside C, 501. C37H62N4O7S3 – Hoiamide C, 855. C37H62N4O8 – Veraguamide G, 706. C37H62N7O16P – Celebeside A, 500. C37H63BrN4O8 – Tetrahydroveraguamide A, 682. C37H63N5O7 – Desacetylmicrocolin B, 195. C37H67N5O9 – Kailuin B, 744. – Kailuin C, 745.

Index 2 Compound Molecular Formula Index

C37H68N4O9 – Ggeopeptide A, 844. – Ggeopeptide C, 846. C38 C38H41N3O5 – Cryptoechinuline D, 21. – (−)-Cryptoechinuline D, 22. – (+)-Cryptoechinuline D, 23. C38H43N3O5 – Dihydrocryptoechinulin D, 40. C38H48N8O6S2 – Patellamide B, 427. – Patellamide D, 429. C38H50BrN7O10 – Bromoalterochromide A, 497. C38H50N8O7S2 – Patellamide G, 432. C38H51BrN4O7 – (+)-Jasplakinolide Z3, 165. C38H51N9O7 – Wainunuamide, 402. C38H52N4O9 – Pullularin F, 376. C38H54N4O6 – Unnarmicin C, 699. C38H55Cl2N3O13S2 – Lyngbyabellin D, 796. C38H56N8O8 – Axinastatin 1, 268. C38H58Cl2N6O8 – Itralamide B, 578. C38H61N7O9 – Anabaenopeptin I, 471. C38H62N4O8 – Kulomoopunalide 2, 617. – Veraguamide D, 703. C38H67N7O13 – Amphibactin S, 177. C38H69N7O14 – Amphibactin B, 176. C38H70N4O8 – Gageotetrin C, 843. C38H70N4O9 – Ggeopeptide D, 847. C39 C39H50N8O5S3 – Tawicyclamide A, 458.

C39H50N8O6S2 – Patellamide E, 430. C39H57N3O6S7 – Lissoclibadin 1, 959. C39H58N8O8 – Axinastatin 2, 269. C39H59N7O15 – Citronamide A, 190. – Citronamide B, 191. C39H62N6O6 – Almiramide B, 173. C39H64N4O8 – Kulomoopunalide 1, 616. – Veraguamide E, 704. C39H64N6O7 – Almiramide A, 172. C39H64N8O14 – Nagahamide A, 637. C39H65N5O8 – Microcolin B, 218. C39H65N5O9 – Microcolin A, 217. C39H69N5O9 – Kailuin D, 746. C39H71N5O9 – Kailuin E, 747. C39H72N4O8 – Gageotetrin B, 842. C39H72N4O9 – Ggeopeptide B, 845. C40 C40H32O15 – Kelletinin A, 895. C40H49ClN8O12 – Microsclerodermin D, 332. C40H53N5O7 – Exumolide B, 554. C40H54N8O7 – Unguisin A, 400. C40H57N5O6 – Carmabin A, 189. C40H57N5O10 – Motuporin, 343. C40H57N7O13S – Tiglicamide C, 696. C40H58Cl2N4O11S2 – Lyngbyabellin N, 856. C40H60N8O8 – Axinastatin 3, 270.

453

454

Index 2 Compound Molecular Formula Index

C40H60N10O9 – Cyclotheonamide E3, 304. C40H61BrN8O9 – Konbamide, 478. C40H61N7O8 – Stylopeptide 1, 387. C40H62N6O9 – Tasipeptin B, 832. C40H66N4O9 – Symplostatin 3, 231. C40H66N6O6 – Almiramide C, 174. C40H68N4O8 – Malevamide D, 215. C41 C41H49N7O6S – trans,trans-Ceratospongamide, 418. – cis,cis-Ceratospongamide, 419. C41H50ClN9O13 – Microsclerodermin C, 331. C41H55N5O7 – Exumolide A, 553. C41H55N5O9 – Pullularin C, 375. C41H55N7O9 – Phakellistatin 4, 363. C41H59N7O12 – Largamide A, 621. C41H59N7O9 – Anabaenopeptin J, 472. C41H60N4O8 – Hantupeptin A, 571. – Veraguamide F, 705. C41H60N8O9 – Anabaenopeptin C, 467. C41H60N8O10 – Nodularin, 345. C41H60N10O9 – Anabaenopeptin B, 466. C41H60N10O9S – Oscillamide B, 481. C41H61N7O7 – (cis)-Rolloamide A, 377. – (trans)-Rolloamide A, 378. C41H62N4O8 – Hantupeptin B, 572.

C41H63N11O21S – Pseudoalterobactin A, 372. C41H63N13O21S – Pseudoalterobactin B, 373. C41H64N4O8 – Hantupeptin C, 573. C41H67N5O9 – Dolastatin 17, 547. C42 C42H40N6O4 – Brevianamide S, 14. C42H54N8O9 – Phakellistatin 3, 362. C42H55N5O7 – Guineamide G, 565. C42H55N7O13S2 – Scleritodermin A, 457. C42H56N8O9 – Axinellin A, 273. C42H56N10O9 – Cyclotheonamide E2, 303. C42H57N5O7 – Cocosamide A, 288. – Cocosamide B, 289. C42H57N5O9 – Pullularin A, 374. C42H61N7O7S – Mollamide A, 453. C42H62N8O8 – Axinastatin 4, 271. C42H62O12S4 – Pentaporin A, 978. C42H66N8O11 – Jimycin B, 602. C42H67N7O10 – Tasiamide A, 232. C42H67N11O14S – Cupolamide A, 293. C42H68N6O6S – Dolastatin 10, 196. C42H69N5O10 – Viequeamide A, 707. C42H72N10O20 – Aquachelin J, 180. C42H77N13O13 – Callipeltin I, 186. C42H79N13O14 – Callipeltin F, 183.

Index 2 Compound Molecular Formula Index

C43 C43H53ClN8O13 – Pedein A, 349. C43H54N8O13 – Pedein B, 350. C43H56N10O11S – Keramamide F, 446. – Keramamide G, 447. C43H57BrN10O12S – Keramamide H, 448. C43H58ClN5O7 – Chloropullularin E, 285. C43H58N10O9 – Cyclotheonamide E, 302. C43H58N10O11S – Keramamide J, 449. C43H62N2O14S5 – Namenamicin, 976. C43H62N6O12 – Salinamide E, 666. C43H63BrN10O14 – Perthamide B, 351. C43H63N5O9 – Kulolide 1, 613. – Pitipeptolide D, 655. – Pitipeptolide E, 656. – Pitipeptolide F, 657. C43H63N7O8S – Trunkamide A, 460. C43H63N11O18S – Perthamide G, 356. C43H64N6O19 – Nobilamide B, 221. C43H65N5O7S – Apratoxin E, 775. C43H65N5O9 – Deoxymajusculamide D, 194. – Kulolide 2, 614. C43H65N5O10 – Majusculamide D, 214. C43H67N5O8S – Apratoxin G, 777. C43H67N5O9 – Kulolide 3, 615. C43H70N6O6S – Symplostatin 1, 230. C43H70N8O7S2 – Microcionamide A, 327. – Microcionamide B, 328.

C43H72N8O9 – Dominicin, 314. C43H73N5O10 – Aurilide C, 493. C43H79N7O8 – Halovir E, 206. C43H79N7O9 – Halovir B, 203. – Halovir D, 205.

C44 C44H55N9O15S2 – Oriamide, 454. C44H57N7O9 – Anabaenopeptin D, 468. C44H57N7O10 – Anabaenopeptin A, 465. C44H57N7O12 – Tiglicamide B, 695. C44H58N8O8 – Euryjanicin A, 315. C44H60N10O11S – Keramamide K, 450. C44H62N8O11 – Jimycin A, 601. – Jimycin C, 603. C44H62N10O15 – Perthamide J, 359. C44H63N7O12S – Nodulapeptin B, 480. C44H63N7O13S – Nodulapeptin A, 479. C44H65N5O9 – Pitipeptolide A, 652. C44H65N9O9 – Tauramamide, 234. C44H65N11O15 – Perthamide H, 357. C44H65N11O17S – Perthamide D, 353. C44H65N11O18S – Mutremdamide A, 344. – Perthamide C, 352. C44H67N5O8S – Apratoxin B, 772. – Apratoxin C, 773. C44H67N5O9 – Pitipeptolide B, 653.

455

456

Index 2 Compound Molecular Formula Index

C44H67N5O10 – Kulokekahilide 2, 612. C44H68N6O8 – Ulongapeptin, 697. C44H69N5O8S – Apratoxin F, 776. C44H69N5O9 – Pitipeptolide C, 654. C44H71N5O10S3 – Hoiamide A, 790. C44H73N11O19 – Loihichelin A, 208. C44H75N5O10 – Aurilide, 491. – Aurilide B, 492. C44H76N10O21 – Aquachelin I, 179. C44H78N10O11 – Aspereline B, 240. – Aspereline C, 241. – Aspereline D, 242. C45 C45H50N4O12S3 – Shishijimicin B, 987. C45H50N4O12S4 – Shishijimicin C, 988. C45H54N8O12 – Microsclerodermin G, 335. C45H54N8O14 – Microsclerodermin E, 333. C45H56N8O12 – Microsclerodermin F, 334. C45H59N7O10 – Oscillamide Y, 483. C45H59N7O13 – Tiglicamide A, 694. C45H61N7O8 – Phakellistatin 1, 360. – Phakellistatin 2, 361. C45H61N11O12S – Calyxamide A, 439. – Calyxamide B, 440. C45H64N8O10 – Brunsvicamide C, 475. C45H64N10O10S2 – Kororamide, 451. C45H64N10O15 – Perthamide K, 408.

C45H67N5O7S – (E)-Dehydroapratoxin A, 780. C45H67N7O10 – Anabaenopeptin T, 473. C45H67N11O15 – Perthamide I, 358. C45H67N11O17S – Perthamide F, 355. C45H67N11O18S – Perthamide E, 354. C45H68N6O9 – Dolastatin 15, 197. C45H68N12O14 – Mixirin B, 341. C45H69N5O10 – Lagunamide B, 619. C45H69N5O8S – Apratoxin A, 770. C45H69N5O9S – Apratoxin A sulfoxide, 771. C45H71N5O10 – Lagunamide A, 618. C45H71N7O10 – Tasipeptin A, 831. C45H73N5O10S3 – Hoiamide B, 791. C45H77N5O10 – Viridamide B, 854. C45H80N10O11 – Aspereline A, 239. C45H80N10O12 – Aspereline E, 243. C45H83N7O8 – Halovir C, 204. C45H83N7O9 – Halovir A, 202. C46 C46H52N4O12S4 – Shishijimicin A, 986. C46H56N8O12 – Microsclerodermin I, 337. C46H58N8O12 – Microsclerodermin H, 336. C46H61N7O13 – Largamide B, 622. C46H62BrN9O10 – Orbiculamide A, 346.

Index 2 Compound Molecular Formula Index

C46H62N8O12 – Somamide B, 830. C46H63ClN8O12 – Cyanopeptolin 954, 801. C46H63N7O12 – Dolastatin 13, 803. C46H66N8O8 – Brunsvicamide B, 474. C46H67N5O8 – Bouillonamide, 496. C46H67N7O11 – Kahalalide A, 604. C46H69N5O10 – Palauamide, 348. C46H70N10O10 – Anabaenopeptin H, 470. C46H71BrN10O13 – Symplocamide A, 678. C46H71N5O8S – Apratoxin H, 778. C46H73BrN8O11 – Kempopeptin B, 606. C46H73BrN10O12S – Pompanopeptin A, 660. C46H73N5O10 – Lagunamide C, 620. C46H75N11O19 – Loihichelin C, 210. C46H77N11O19 – Loihichelin D, 211. C46H77N11O20 – Loihichelin B, 209. C46H79N5O10 – Viridamide A, 853. C46H82N10O11 – Aspereline F, 244. C47 C47H62N8O7 – Phakellistatin 6, 365. C47H62N8O15 – Microsclerodermin B, 330. C47H62N8O16 – Microsclerodermin A, 329. C47H63N7O13 – Largamide C, 623. C47H64N8O12 – Lyngbyastatin 8, 813.

C47H65N9O11 – Discobahamin A, 403. C47H68N10O18S – Oscillapeptin J, 826. C47H69N9O9 – Phakellistatin 10, 369. C47H70N6O4 – Dolastatin 16, 546. C47H72N8O9 – Axinastatin 5, 272. – Hymenistatin 1, 318. C47H72N12O14 – Mixirin C, 342. C47H74N12O14 – Callipeltin B, 499. C47H78N6O7 – Kurahyne, 848. C48 C48H56N10O11S6 – 22ʹ-Deoxythiocoraline, 533. C48H56N10O12S6 – Thiocoraline, 693. C48H56N10O13S6 – 12ʹ-Sulfoxythiocoraline, 677. C48H63N7O8 – Cordyheptapeptide C, 290. C48H66N8O12 – Lyngbyastatin 7, 626. C48H66N8O13 – Molassamide, 819. C48H67N7O12S – Somamide A, 829. C48H67N9O11 – Discobahamin B, 404. C48H70N6O10 – Kulokainalide 1, 610. C48H72N6O10 – Homodolastatin 16, 316. C48H74N12O14 – Mixirin A, 340. C48H75N5O8S – Apratoxin D, 774. C48H75N7O13 – Thalassospiramide A, 767. C48H79N11O19 – Loihichelin E, 212. C48H81N11O19 – Loihichelin F, 213.

457

458

Index 2 Compound Molecular Formula Index

C49 C49H52N8O6 – Kapakahine B, 320. C49H63ClN8O8 – Keramamide L, 477. C49H63ClN8O9 – Keramamide A, 476. C49H63N7O8 – Stylissatin A, 386. C49H65N7O9 – Cordyheptapeptide E, 291. C49H67BrN8O12 – Bouillomide B, 800. C49H67N7O11 – Anabaenopeptin G, 469. C49H68N8O12 – Bouillomide A, 799. C49H68N10O10 – Oscillamide C, 482. C49H69N7O13 – Cyanopeptolin 963 A, 802. C49H72N10O13 – (D-Asp,ADMAdda5)Microcystin LR, 264. C49H78N6O12 – Didemnin A, 538. – epi-Didemnin A1, 539. C49H78N8O11 – Desmethoxymajusculamide C, 535. C49H78N8O12 – 57-Normajusculamide C, 645. C49H80N6O13 – Acyclodidemnin A, 171. C50 C50H47N15O13S3 – TP-1161, 798. C50H67N7O7 – Scytalidamide A, 381. C50H67N7O15 – Salinamide D, 665. C50H67N9O9 – Axinellin B, 274. C50H70BrN7O8S – Norbisebromoamide, 222. C50H70N8O13 – Kempopeptin A, 605. C50H73N5O10 – Pitiprolamide, 658.

C50H74N8O12 – Tasiamide B, 233. C50H74N10O13 – (ADMAdda5)Microcystin LR, 263. C50H77N13O14 – Mojavensin A, 849. C50H78N6O12 – N,N’-Methyleno-didemnin A, 628. C50H80N8O11 – Dolastatin 12, 545. C50H80N8O12 – Dolastatin 11, 544. – Majusculamide C, 627. C50H82N8O12 – Grassystatin C, 253. C51 C51H69N7O7 – Scytalidamide B, 382. C51H69N7O15 – Salinamide A, 827. C51H69N9O9 – Phakellistatin 19, 371. – Stylissamide X, 385. C51H70ClN7O15 – Salinamide B, 828. C51H72BrN7O8S – Bisebromoamide, 181. C51H76N8O16S – Oscillapeptin F, 825. C51H76N10O13 – (ADMAdda5)Microcystin LHar, 262. C51H80N12O11S3 – Cycloforskamide, 442. C51H82N8O11 – Ibu-epi-demethoxylyngbyastatin 3, 575. C51H82N8O12 – Lyngbyastatin 1, 624. C51H89N7O13 – Gageostatin C, 840. C51H93N9O11 – N-Methylated octapeptide RHM3, 216. C52 C52H73BrN10O15S – Keramamide M, 406. C52H73N7O14 – Salinamide C, 664.

Index 2 Compound Molecular Formula Index

C52H76N4O8S12 – Lissoclibadin 8, 965. C52H82ClN11O15 – Phoriospongin A, 650. C52H82N6O14 – Didemnin C, 541. C52H85N7O11 – Wewakpeptin A, 709. C52H89N7O11 – Wewakpeptin B, 710. C52H93N7O14 – Gageostatin A, 838. C53 C53H67N9O9 – Phakellistatin 11, 370. C53H68N8O15 – Lyngbyastatin 5, 811. C53H68N8O18S – Lyngbyastatin 4, 810. C53H74N6O10 – Kulokekahilide 1, 611. C53H75BrN10O12 – Keramamide E, 405. C53H75BrN10O15S – Keramamide N, 407. C53H83N7O14 – Tamandarin B, 680. C53H84ClN11O15 – Phoriospongin B, 651. C53H86N8O10 – Wewakamide A, 708. C53H87N9O10 – Clonostachysin A, 286. C53H93N7O13 – Bacillus pumilus KMM 1364 Lipodepsipeptide A, 721. – Bacillus pumilus KMM 1364 Lipodepsipeptide B, 722. C53H93N9O16 – Massetolide E, 753. C53H94N8O12 – Halobacillin, 729. C53H95N7O14 – Gageostatin B, 839. C54 C54H70N8O18S – Lyngbyastatin 6, 812.

459

C54H77N7O17S – Oscillapeptin D, 823. C54H81N7O11 – Wewakpeptin C, 711. C54H81N11O10 – Callyaerin H, 284. C54H85N7O11 – Wewakpeptin D, 712. C54H85N7O14 – Tamandarin A, 679. C54H89N9O10 – Clonostachysin B, 287. C54H95N7O13 – Bacillus pumilus KMM 1364 Lipodepsipeptide C, 723. – Bacillus pumilus KMM 1364 Lipodepsipeptide D, 724. C54H95N9O16 – Massetolide F, 754. – Viscosin, 768. C54H100N16O17 – Callipeltin G, 184. C55 C55H75N7O17S – Oscillapeptin E, 824. C55H77N9O10S2 – Grassypeptolide B, 782. C55H77N9O15 – Kurahamide, 804. C55H79N7O14 – Oscillapeptin C, 822. C55H85N7O15 – Didemnin N, 543. C55H92N6O13 – Norlyngbyastatin 2, 644. C55H97N7O13 – Bacillus pumilus KMM 1364 Lipodepsipeptide E, 725. C55H97N9O16 – Massetolide A, 749. – Massetolide D, 752. – Massetolide G, 755. C56 C56H77N7O18S – Oscillapeptin A, 820. C56H79N9O10S2 – Grassypeptolide A, 781.

460

Index 2 Compound Molecular Formula Index

– Grassypeptolide C, 783. C56H80BrN9O16 – Largamide D oxazolidine, 806. C56H82BrN9O17 – Largamide D, 805. C56H82ClN9O17 – Largamide E, 807. C56H82N8O11 – Cyclomarin A, 296. C56H86N8O13 – Symplocin A, 229. C56H88N8O10 – Antibiotic IB 01212, 489. C56H94N6O13 – Lyngbyastatin 2, 625. – Nordolastatin G, 643. C56H99N7O13 – Bacillus pumilus KMM 1364 Lipodepsipeptide F, 726. – Bacillus pumilus KMM 1364 Lipodepsipeptide G, 727. C56H99N9O16 – Massetolide B, 750. – Massetolide H, 756. C57 C57H57N9O8 – Kapakahine E, 322. C57H79N7O18S – Oscillapeptin B, 821. C57H81N9O10S2 – Grassypeptolide D, 784. – Grassypeptolide E, 785. C57H87N7O15 – Aplidine, 490. C57H89N7O15 – Didemnin B, 540. – [D-Pro4]Didemnin B, 663. C57H96N6O13 – Dolastatin G, 549. C57H96N6O18 – Bacillistatin 1, 494. – Bacillistatin 2, 495. – Cereulide, 502. C57H101N9O16 – Massetolide C, 751.

C58 C58H72N10O10 – Kapakahine C, 321. C58H72N10O8 – Kapakahine A, 319. C58H83N11O10 – Callyaerin F, 282. C58H95N9O16 – Grassystatin A, 251. C58H98N6O18 – Homocereulide, 574. C59 C59H68N14O9 – Plicatamide, 223. C59H77N9O9S2 – Grassypeptolide G, 787. C59H80BrN9O18 – Largamide F, 808. C59H84N10O11 – Phakellistatin 7, 366. C59H92N8O11 – Dolastatin 14, 728. C59H96N8O24 – Mollemycin A, 850. C59H97N9O16 – Grassystatin B, 252. C59H107N7O11 – Peptidolipin B, 851. C59H108N10O12 – Trichoderin B, 238. C60 C60H79N9O9S2 – Grassypeptolide F, 786. C60H82BrN9O18 – Largamide G, 809. C60H86N10O11 – Phakellistatin 9, 368. C60H94N8O11 – Malevamide E, 748. C60H97N11O14 – Hormothamnin A, 317. C60H98N6O14 – Onchidin, 646. C60H108N10O11 – Trichoderin A1, 237.

Index 2 Compound Molecular Formula Index

C60H110N10O12 – Trichoderin A, 236.

C62 C62H88N14O21 – Aciculitin B, 260. C62H99N11O24 – Hassallidin A, 730.

C66H104ClN13O21 – Mirabamide C, 758. C66H104N14O21 – Stellatolide F, 765. C66H104N14O22 – Stellatolide G, 766. C66H105N13O21 – Papuamide A, 648. C66H107N15O21 – Stellatolide D, 763. C66H107N15O22 – Stellatolide A, 760. C66H109N15O23 – Stellatolide C, 762.

C63 C63H90N14O21 – Aciculitin C, 261. C63H93N15O13 – Callyaerin C, 279. C63H108N12O15 – Dictyonamide A, 246. C63H115N7O11 – Peptidolipin D, 852.

C67 C67H85N13O14 – Loloatin B, 324. C67H85N13O15 – Loloatin D, 326. C67H102N10O19 – Didemnin M, 542. C67H116N18O21 – Callipeltin K, 188.

C65 C65H84N12O15 – Loloatin A, 323. C65H103N13O21 – Papuamide B, 649. C65H105N15O22 – Stellatolide B, 761. – Stellatolide E, 764. C65H109N13O13 – Callyaerin B, 278. C65H110N10O16 – Coibamide A, 504.

C68 C68H96BrN17O17S – Halicylindramide E, 254. C68H105N15O15 – Callyaerin D, 280. C68H116N18O20 – Callipeltin H, 185. – Callipeltin A, 498. C68H118N18O21 – Callipeltin C, 182. C68H121N13O16 – Theonellapeptolide If, 688.

C66 C66H95N5O19 – Tausalarin C, 681. C66H95N13O12 – Callyaerin E, 281. C66H100N12O15 – Koshikamide A1, 207. C66H102ClN13O19 – Mirabamide H, 635. C66H102ClN13O20 – Mirabamide G, 634.

C69 C69H86N14O14 – Loloatin C, 325. C69H87BrN16O22 – Theonellamide C, 392. C69H91N13O12 – Callyaerin G, 283. C69H108N14O14 – Callyaerin A, 277. C69H123N13O16 – Theonellapeptolide Ia, 683.

C61 C61H86N14O21 – Aciculitin A, 259. C61H88N10O11 – Phakellistatin 8, 367.

461

462

Index 2 Compound Molecular Formula Index

– Theonellapeptolide Ib, 684. – Theonellapeptolide Ic, 685. – Theonellapeptolide IId, 689. C69H123N13O16S – Sulfinyltheonellapeptolide, 676. C69H123N17O23 – Theopapuamide A, 690. C70 C70H89BrN16O23 – Theonellamide B, 391. C70H101BrN16O26 – Theonegramide, 389. C70H125N13O15 – 33-Demethoxytheonellapeptolide Ie, 532. C70H125N13O16 – Theonellapeptolide Id, 686. C70H125N13O16S – 33-Demethoxy-33-(methylsulfinyl) theonellapeptolide Id, 531. C71 C71H118N18O22 – Neamphamide C, 640. C71H119N19O21 – Neamphamide B, 639. C71H125N17O23 – Theopapuamide C, 692. C71H125N17O24 – Theopapuamide B, 691. C71H127N13O16 – Theonellapeptolide IIIe, 395. – Theonellapeptolide Ie, 687. C72 C72H105N13O20 – Pahayokolide A, 347. C72H111ClN12O25 – Mirabamide B, 757. C72H112ClN13O23 – Mirabamide F, 633. C72H112ClN13O24 – Mirabamide E, 632. C72H112N16O16 – Koshikamide A2, 256. C72H114ClN13O25 – Mirabamide A, 631. C72H115N13O25 – Mirabamide D, 759.

C72H121N19O21 – Neamphamide D, 641. C72H125N15O24 – Homophymine B, 733. C72H126N16O23 – Homophymine B1, 734. C73 C73H100BrN19O20S – Halicylindramide D, 570. C73H127N15O24 – Homophymine A, 731. C73H128N16O23 – Homophymine A1, 732. C74 C74H95Br2N16O271+ – Theonellamide D, 393. C74H129N15O24 – Homophymine C, 735. C74H130N16O23 – Homophymine C1, 736. C75 C75H97Br2N16O28 – Theonellamide E, 394. C75H109BrN18O22S – Microspinosamide, 630. C75H110BrN19O20S – Polydiscamide A, 659. C75H112N20O22S – Discodermin D, 309. C75H124N14O16 – Isokahalalide F, 577. – Kahalalide F, 741. C75H125N21O23 – Neamphamide A, 638. C75H131N15O24 – Homophymine D, 737. C75H132N16O23 – Homophymine D1, 738. C76 C76H99BrN16O27 – Theopalauamide, 396. C76H99BrN16O281+ – Theonellamide A, 390. C76H114N20O22S – Discodermin B, 307. – Discodermin C, 308.

Index 2 Compound Molecular Formula Index

C76H116N20O23S – Discodermin E, 310. C76H133N15O24 – Homophymine E, 739. C76H134N16O23 – Homophymine E1, 740. C77 C77H109N17O20 – Sungsanpin, 769. C77H114N14O21S – Vitilevuamide, 833. C77H116N20O22S – Discodermin A, 306. C77H116N20O23S – Discodermin H, 313. C77H126N14O17 – Kahalalide R, 742. C78 C78H109BrN20O22S – Halicylindramide A, 567. – Halicylindramide B, 568. C78H118N20O22S – Discodermin F, 311. – Discodermin G, 312. C79 C79H111BrN20O22S – Halicylindramide C, 569. C80 C80H142N16O16 – Bogorol A, 245. C81 C81H139N18O161+ – Efrapeptin J, 250. C82 C82H100N14O24 – Microviridin E, 818.

C82H141N18O161+ – Efrapeptin F, 248. C82H142N18O16 – Efrapeptin Eα, 247. C83 C83H134N14O15S2 – Kendarimide A, 255. C83H143N18O161+ – Efrapeptin G, 249. C84 C84H106N16O24 – Microviridin B, 815. C84H107N17O26S – Microviridin D, 817. C85 C85H100N16O24 – Microviridin A, 814. C85H110N16O25 – Microviridin C, 816. C93 C93H148N24O27 – Koshikamide F, 608. C93H150N24O28 – Koshikamide B, 607. C94 C94H152N24O28 – Koshikamide H, 609. C129 C129H183N35O39S7 – Neopetrosiamide A, 257. – Neopetrosiamide B, 258.

463

Index 3 Compound Organism Source Index This index lists in alphabetical order all xxx marine organism in Latin names in HAMNP Volume 8, 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 255 of this index, one will know that the Haliclona sp. is a sponge. A Acanthus ilicifolius 124, 168, 169. Aciculites orientalis 259, 260, 261. Acremonium persicinum 290, 291. Acremonium sp. 216, 247, 248, 249. Acrostalagmus luteoalbus SCSIO F457 973, 974. Acrostichum aureum 3, 63. Adocia sp. 1003, 1004. Agarum cribrosum 35, 932. Agelas clathrodes 1005. Agelas nakamurai 1005. Agelas sp. 1005. Alexandrium excavatum 871. Alsidium helminthochorton 863. Alternaria raphani 1. Alternaria sp. SF-5016 487. Alteromonas luteoviolacea 175, 488. Alteromonas rava 992, 993, 994, 995, 1029. Anabaena flos-aquae NRC525.17 465. Anabaena flos-aquae NRC525-17 466. Anabaena sp. 202A2 468. Anabaena sp. 90 465, 467. Anabaena spiroides 167. Analipus japonicus 120, 153. Anisodoris nobilis 907. Annella sp. 2. Anthocidaris crassispina 6. Aphanizomenon flos-aquae 471. Aphanizomenon flos-aquae NIES 81 472. Aplidium albicans 490. Aplidium conicum 1008, 1009, 1026, 1027. Aplidium fuscum 915. Aplidium multiplicatum 913. Aplidium sp. 935, 1006, 1007. Aplysia pulmonica 443. Ascidia nigra 125. Aspergillus aculeatus [Syn. Xestospongia testudinaria] CRI323-04 873. Aspergillus effuses H1-1 21, 22, 23, 37, 40, 41.

Aspergillus elegans 864. Aspergillus fumigatus 10, 43, 52, 53, 54, 66, 72, 97, 98, 99, 100, 103, 118. Aspergillus fumigatus BM939 95, 96, 102. Aspergillus fumigatus YK-7 55. Aspergillus insuetus 4. Aspergillus insulicola 5. Aspergillus sclerotiorum PT06-1 379, 380. Aspergillus sclerotiorum sp. 080903f04 267. Aspergillus sp. 51, 59, 61, 62, 124, 265, 872. Aspergillus sp. 16-02-1 1031. Aspergillus sp. CMB-M081F 94. Aspergillus sp. W-6 124, 168, 169. Aspergillus sydowi PFW1-13 42, 56, 60, 65, 95, 101, 118. Aspergillus taichungensis ZHN-7-07 3, 63. Aspergillus terreus 95F-1 124. Aspergillus terreus SCSGAF016 266. Aspergillus variecolor 104, 105, 106, 107, 108, 109, 111, 112, 113, 114. Aspergillus versicolor 13, 13, 14, 45, 156, 157. Aspergillus versicolor ATCC 9577 908, 909. Aspergillus versicolor CXCTD-06-6a 13, 15. Aspergillus versicolor HDN08-60 119. Aspergillus versicolor MST-MF495 292. Aspergillus versicolor ZBY-3 29, 30, 32, 33. Aspergillus westerdijkiae DFFSCS013 12, 64. Asterias rubens 893. Asterina bather 901, 902, 903. Auletta cf. constricta 579. Auletta sp. 161. Auletta sp. 02137 579, 580, 583, 584, 593, 594, 598. Aureobasidium pullulans 28. Avrainvillea longicaulis 928, 930. Avrainvillea sp. 629. Axinella carteri 273, 274, 318. Axinella cf. carteri 271, 272. Axinella sp. 268, 269, 270.

Index 3 Compound Organism Source Index

B Bacillus cereus SCRC-4h1-2 502, 574. Bacillus licheniformis 890, 891. Bacillus mojavensis 849. Bacillus pumilus KMM 1364 721, 722, 723, 724, 725, 726, 727. Bacillus silvestris 494. Bacillus sp. 6, 399, 892. Bacillus sp. CND-914 729. Bacillus sp. MIX-62 340, 341, 342. Bacillus subtilis 838, 839, 840, 841, 842, 843, 844, 845, 846, 847. Beauveria felina 484, 485, 486. Beauveria felina EN-135 536, 537, 576. Bionectria ochroleuca 285, 374, 375, 376, 1002. Blastobacter sp. SANK 71894 919. Blennothrix cantharidosmum 887, 888, 889. Brevibacillus laterosporus 234. Brevibacillus laterosporus PNG-276 245. Bryopsis pennata 577. Bryopsis sp. 604, 741. Buccinulum corneum 895. Bugula sp. 338, 339. Bursatella leachii 779, 789. C Calliostoma canaliculatum 920. Callipelta sp. 182, 498, 499. Callyspongia aerizusa 277, 278, 279, 280, 281, 282, 283, 284. Callyspongia bilamellata 650, 651. Calyx cf. podatypa 30, 31. Cassiopeia xamachana 664, 665, 666, 827, 828. Caulerpa sp. 484. Centroceras clavulatum 863. Ceratodictyon spongiosum 246, 418, 419. Chlamys hastata 866. Chondria californica 937, 991, 996, 1019, 1020, 1028. Chondrilla caribensis f. caribensis 235, 533, 677, 693. Chondromyces crocatus Cmc5 503. Chondromyces pediculatus 349, 350. Citronia astra 190, 191. Cladiella australis 1011. Cladosiphon okamuranus 1032. Clonostachys rogersoniana HJK9 286, 287.

465

Clonostachys sp. ESNA-A009 489. Codium decorticatum 857. Collocalia mucoid 893. Cribricellina cribraria 1012. Cribrochalina olemda 319, 320, 321, 322. Cymbastela sp. 159, 160, 192, 193, 555, 556, 557, 558, 559, 560, 561, 579. Cystodytes dellechiajei 297. Cytophaga sp. 876. D Dasychalina cyathina 904, 905. Diazona cf. formosa 989, 990. Dichothrix utahensis 819. Didemnum cucculiferum 833. Didemnum molle 420, 421, 441, 453. Didemnum proliferum 976, 986, 987, 988. Didemnum rodriguesi 47. Didemnum sp. 74, 75, 679, 680. Digenea simplex 858, 863. Diplosoma virens 128. Discodermia calyx 439, 440. Discodermia kiiensis 306, 307, 308, 309, 310, 311, 312, 313. Discodermia sp. 403, 404, 659. Dolabella auricularia 196, 197, 422, 443, 491, 544, 545, 546, 547, 548, 550, 627, 728, 803, 874. Dysidea arenaria 515. Dysidea fragilis 46. Dysidea sp. 142, 871. E Echinodictyum sp. 869, 1010. Ecionemia acervus 760, 761, 762, 763, 764, 765, 766. Ectyoplasia ferox 563, 564. Elysia grandifolia 742. Elysia rufescens 604, 741. Emericella sp. CNL-878 551, 552. Emericella unguis 400, 401. Enteromorpha intestinalis 857. Eurotium cristatum EN-220 18, 19, 20. Eurotium rubrum 34, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 110. Eurotium rubrum MA-150 76, 77, 78. Eurypon laughlini 314, 377, 378. Euthyroides episcopalis 1014, 1015, 1016.

466

Index 3 Compound Organism Source Index

Evasterias troschelii 865. Exserohilum rostratum 982, 983, 984, 985. F Fascaplysinopsis sp. 681. Fusarium sp. 667. Fusarium sp. CNL-619 629. G Geodia barretti 7, 16, 38, 910, 911. Geodia sp. 555, 556, 562. Gliocladium sp. 36, 48, 49, 50. Gliocladium sp. YUP08 36. Grateloupia carnosa 860. Grateloupia filicina 1018. Gymnangium regae 201. H Halichondria cylindrata 254, 567, 568, 569, 570. Haliclona sp. 255, 566, 788. Haliclona sp. (order Haptosclerida, family Chalinidae) 566. Halocynthia aurantium 721, 722, 723, 724, 725, 726, 727. Halocynthia roretzi 1032. Halomonas meridiana 179, 180. Halomonas sp. LOB-5 208, 209, 210, 211, 212, 213. Halosarpheia sp. 732 463, 464. Hassallia sp. 730. Hemiasterella minor 158, 579. Hibiscus tiliaceus 34, 110. Holodule wrightii 667. Homophymia sp. 731, 732, 733, 734, 735, 736, 737, 738, 739, 740. Hormothamnion enteromorphoides 317. Hymeniacidon sp. 318, 360, 837. Hyphomycetes sp. CR28109 873. Hypnea valendiae 906. Hypsistozoa fasmeriana 936. Hyrtios sp. 861. I Ianthella sp. 563, 564. Iotrochota purpurea 877, 878, 879, 880, 881, 882, 883, 884, 885, 886. Ircinia sp. 302. Iridaea laminaroides 900. Isodictya erinacea 870.

J Janolus cristatus 162. Jaspis johnstoni 579, 916. Jaspis sp. 579, 579, 579. Jaspis splendans 590, 591, 592. Jaspis splendens 163, 164, 165, 166, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 593, 595, 596, 597, 599, 600. Jaspis splendens 00101 584. Jaspis spp. 916. K Kandelia candel 534. Kelletia kelletii 894, 896. L Lamellodysidea chlorea 144, 145, 146. Lamellomorpha strongylata 395. Latrunculia magnifica 859. Latrunculia sp. 183, 184, 185, 186, 187, 188, 498, 499. Latrunculia wellingtonensis 925, 926. Laurencia pinnatifida 900. Leptolyngbya sp. 504, 545, 575, 784, 785. Leptosphaeria sp. 941, 942, 943. Leptosphaeria sp. OUPS-4 938, 939, 940, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956. Leptosphaeria sp. OUPS-N80 957, 958. Leucetta microraphis 423. Lichina pygmaea 868. Lissoclinum bistratum 410, 411, 412, 413, 414, 415, 416, 417. Lissoclinum cf. badium 959, 960, 961, 962, 963, 964, 965, 966, 967, 968, 968. Lissoclinum japonicum 918, 931. Lissoclinum patella 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 455, 456, 458, 459, 461, 462. Lissoclinum perforatum 969, 970. Lissoclinum sp. 460, 971, 975, 1017. Lissoclinum vareau 997. Littorina sp. 502, 574. Loligo vulgaris 865. Lumbriconereis heteropoda 977. Lyngbya bouillonii 775, 776, 777, 799, 800. Lyngbya cf. confervoides 805, 806. Lyngbya cf. polychroa 195, 217.

Index 3 Compound Organism Source Index

Lyngbya confervoides 251, 252, 253, 621, 621, 622, 622, 623, 623, 660, 694, 695, 696, 781, 782, 783, 797, 810, 811. Lyngbya majuscula 172, 173, 174, 189, 194, 198, 199, 200, 214, 217, 218, 288, 289, 316, 443, 444, 451, 492, 493, 535, 544, 545, 549, 565, 571, 572, 573, 578, 618, 619, 620, 624, 625, 627, 627, 643, 644, 645, 647, 652, 653, 654, 655, 656, 657, 658, 713, 714, 716, 717, 770, 774, 786, 787, 789, 790, 793, 794, 829, 830, 855, 887. Lyngbya semiplena 708, 709, 710, 711, 712, 799, 800, 813. Lyngbya sordida 774. Lyngbya sp. 181, 222, 347, 348, 605, 606, 636, 661, 662, 697, 772, 773, 780, 795, 796, 804, 848. Lyngbya sp. [Syn. Moorea sp.] 804, 848. Lyngbya sp. nov. 347. Lyngbya spp. 626, 811, 812. M Marinactinospora thermotolerans SCSIO 00652 452. Mastocarpus stellatus 900. Melitodes squamata 265. Microcystis aeruginosa 129, 136. Microcystis aeruginosa NEIS 102 130. Microcystis aeruginosa NIES-298 135, 815, 816. Microcystis aeruginosa NIES98 137, 138, 139. Microcystis aeruginosa NIVA Cya 43 801. Microcystis sp. 147. Microcystis sp. IL-323 140, 141. Microcystis sp. PCC 7806 802. Microcystis viridis 814. Microcystis viridis NEIS 102 131, 132. Micromonospora sp. L-13-ACM2-092 693. Microscleroderma sp. 329, 330, 331, 332, 333, 334, 335, 336, 337. Microsporum cf. gypseum 338, 339. Molgula manhattensis 126, 127. Moorea bouillonii 496, 856. Moorea producens 771, 778. Moorea sp. [Syn. Lyngbya sp.] 804, 848. Mycale izuensis 275, 276. Mycale sp. 267, 912. Mytilus edulis 61, 62.

467

N Neamphius huxleyi 638, 639, 640, 641. Neopetrosia sp. 257, 258. Neosiphonia superstes 642. Nigrospora sp. PSU-F12 2. Nocardia sp. 851, 852. Nocardiopsis sp. 295, 798. Nodularia spumigena 345. Nodularia spumigena AV1 479, 480. Nostoc sp. 152 262, 263, 264. Nostoc sp. ATCC 53789 509, 515, 518. Nostoc sp. GSV 224 505, 506, 507, 508, 510, 511, 512, 513, 514, 516, 517, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 530. Nostoc spp. 505. O Occurs in algae, lobsters, sharks and dogfishes etc. 1030. Occurs in eggs, milk, colostrum, submaxillary mucin and meconium 893. Occurs in terrestrial and marine fungi 932. Occurs widely in nature 904. Onchidium sp. 646. Oscillatoria agardhii 483. Oscillatoria agardhii [Syn. Planktothrix agardhii] NIES 595 469. Oscillatoria agardhii B2 83 148. Oscillatoria agardhii NIES 204 466, 817, 818, 820, 821. Oscillatoria agardhii NIES 205 133, 134, 822, 823, 824. Oscillatoria agardhii NIES 26 817, 818. Oscillatoria agardhii NIES 595 469, 470. Oscillatoria agardhii NIES 596 825. Oscillatoria margaritifera 700, 701, 702, 875. Oscillatoria nigroviridis OSC3L 853, 854. Oscillatoria sp. 437, 438, 621, 622, 623, 805, 807, 808, 809. P Padina australis 28. Paecilomyces variotii EN-291 39. Palmaria palmate 871. Palythoa sp. 26. Panuliris longipes cygnus 1030. Paracentrotus lividus 865, 867. Paraliomyxa miuraensis SMH-27-4 636. Penicillium brefeldianum SD-273 73.

468

Index 3 Compound Organism Source Index

Penicillium brocae MA-231 67, 68, 69, 70, 921, 922, 923, 924. Penicillium chrysogenum 17. Penicillium fellutanum 154, 155. Penicillium griseofulvum 37, 115, 116, 117. Penicillium sp. CNC-350 928, 930, 1001. Penicillium sp. JMF034 9, 10, 11, 927, 929, 933, 934. Pentapora fascialis 978. Petrosia ficiformis 4. Petrosia sp. 156, 157, 897. Phakellia carteri 361, 362. Phakellia costata 360, 363, 364, 365, 366, 367, 368, 369, 370, 387. Phakellia sp. 371, 1021. Philinopsis speciosa 610, 611, 612, 613, 614, 615, 616, 617. Phoma sp. OUCMDZ-1847 71. Phoriospongia spp. 650, 651. Phormidium gracile 790, 855. Phormidium spp. 230. Photobacterium sp. MBIC06485 698, 699. Pinctada martensii 849. Plakortis lita 1022, 1023, 1024, 1025. Planktothrix agardhii 481. Planktothrix agardhii [Syn. Oscillatoria agardhii] NIES 595 469. Planktothrix agardhii HUB011 466. Planktothrix rubescens 481, 482, 826. Platynereis dumerilii 865. Pleurobranchus forskalii 442, 445. Plocamium cartilagineum 900. Polycarpa aurata 981. Polycarpa auzata 979, 980. Polycarpa clavata 981. Polycitor sp. 997, 998, 999, 1000. Polysyncraton lithostrotum 833, 976. Porteresia coarctata 17. Prochloron sp. 410, 411, 871. Prosuberites laughlini 314, 315. Psammocinia aff. bulbosa 294. Psammocinia sp. 294. Pseudallescheria sp. 932. Pseudallescheria sp. MFB165 10, 35. Pseudaxinella sp. 268. Pseudaxinyssa sp. 268, 557, 558, 559, 560. Pseudoalteromonas luteoviolacea 28. Pseudoalteromonas maricaloris KMM 636 497.

Pseudoalteromonas sp. KP20-4 372, 373. Pseudomonas fluorescens, various terrestrial and marine 749. Pseudomonas sp. 749, 768. Pseudomonas sp. MK90e85 and MK91CC8 750, 751, 752, 753, 754, 755, 756. Ptilocaulis trachys 627. R Ramalina terebrata 868. Ritterella sigillinoides 1013. Rivularia sp. 707. S Salinispora arenicola 551, 552. Salinispora arenicola CNS-205 296. Salinispora arenicola CNT-088 718, 719, 720. Sarcophyton sp. 864. Sarcotragus sp. 897. Sargassum sp. 59, 124. Sargassum thunbergii 13, 18, 19, 20, 45. Sargassum tortile 938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957, 958. Scenedesmus sp. 31. Schizothrix calcicola 544, 545, 624, 887. Schizothrix sp. 713, 714, 829, 830. Scleritoderma nodosum 457. Scopulariopsis brevicaulis 668, 669. Scytalidium sp. 202, 203, 204, 205, 206, 381, 382, 553, 554. Sidonops microspinosa 630. Sigmadocia symbiotica 418, 419. Siliquariaspongia mirabilis 500, 501, 631, 690, 691, 692, 757, 758, 759. Sinularia sp. 100. Siphonochalina sp. 161. Smenospongia sp. 861. Sonneratia caseolaris 285, 374, 375, 376, 1002. Spicellum roseum 563, 564. Spongosorites sp. 44. Stelleta calvosa 632, 633, 634, 635, 758. Stelletta sp. 25. Stichopus japonicus 43, 52, 53, 66, 97, 98, 99. Streptomyces fungicidicus 916. Streptomyces sp. 24, 27, 120, 153, 221, 601, 602, 603, 769, 834, 850, 916. Streptomyces sp. Act8015 835, 836.

Index 3 Compound Organism Source Index

Streptomyces sp. CHQ-64 58. Streptomyces sp. CNB-091 664, 665, 666, 827, 828. Streptomyces sp. CNB-982 296. Streptomyces sp. CNQ-593 835, 836. Streptomyces tenjimariensis 898, 899. Streptomyces toyocaensis 916. Streptomyces tumescens 398. Streptomyces xanthophaeus 120. Streptomyces xiamenensis 862. Strongylocentrotus purpuratus 867. Styela plicata 223, 1032. Stylissa flabelliformis 272. Stylissa massa 386. Stylissa sp. 385. Stylotella aurantium 360, 387, 402. Stylotella sp. 387, 388. Suberites japonicas 670, 671, 672, 673, 674. Symploca cf. hydnoides 546, 682, 700, 701, 702, 703, 704, 705, 706. Symploca hydnoides 215, 230. Symploca laeteviridis 728, 748. Symploca sp. 150, 151, 152, 229, 232, 233, 678, 792. Symploca sp. NIH304 831, 832. Symploca sp. VP452 231. Symploca sp. VP642 196. Synthetic 529. T Tedania digitata 907. Tedania ignis 30, 31. Terrestrial fungi 857. Terrestrial fungi Aspergillus ochraceus, Streptomyces gancidicus, Candida albicans, Guignardia laricina and Ceratocystis spp. 30. Terrestrial fungi Colletotrichum gloeosporioides and Gliocladium deliquescens 10. Terrestrial fungi Penicillium aurantiogriseum var. aurantiogriseum and Penicillium aurantiogriseum var. neoechinulatum 4. Terrestrial fungi Penicillium spp., Aspergillus caespitosus 118. Terrestrial fungi Rhizoctonia solani and Rosellinia necatrix 31. Terrestrial fungus Aspergillus amstelodam 22. Terrestrial fungus Gliocladium catenulatum 1002.

469

Terrestrial mushroom Lentinus edodes 937, 991. Terrestrial plants in free state 857. Terrestrial unidentified fungus 374, 375. Tethya aurantium 668, 669. Thalassospira sp. CNJ-328 767. Thalysias abietina 327, 328. Theonella aff. mirabilis 170, 219. Theonella cupola 293, 344, 608. Theonella mirabilis 648, 649. Theonella sp. 207, 220, 256, 298, 303, 304, 331, 332, 333, 346, 351, 390, 391, 392, 393, 394, 405, 406, 407, 446, 447, 448, 449, 450, 454, 476, 477, 478, 531, 532, 607, 686. Theonella spp. 648, 649. Theonella swinhoei 224, 225, 226, 227, 228, 299, 300, 301, 302, 305, 343, 352, 353, 354, 355, 356, 357, 358, 359, 389, 396, 408, 608, 609, 637, 648, 649, 675, 676, 683, 684, 685, 686, 687, 688, 689, 690. Theonella swinhoei ssp. swinhoei 344. Theonella swinhoei ssp. verrucosa 344. Tolypocladium sp. AMB18 250. Tolypothrix sp. 189. Trachycladus laevispirulifer 917. Trichoderma asperellum Y19-07 239, 240, 241, 242, 243, 244. Trichoderma reesei 397. Trichoderma sp. 05F148 236, 237, 238. Trididemnum cyanophorum 540, 542, 543, 663. Trididemnum orbiculatum 851, 852. Trididemnum solidum 171, 490, 538, 539, 540, 543, 628. Trididemnum sp. 538, 541. Trididemnum spp. 541. Tychonema sp. 474, 475. U Ulva lactuca 857. Unidentified actinomycete K-26 149. Unidentified ascidian 409, 433, 972. Unidentified cyanobacterium 197, 473, 715. Unidentified cyanobacterium PNG-4-28-06-1 791. Unidentified fish 154, 155. Unidentified fungus 001314c 563, 564. Unidentified jellyfish 400, 401.

470

Index 3 Compound Organism Source Index

Unidentified mangrove 21, 22, 23, 37, 41, 463, 464. Unidentified mangrove-derived fungus 1962 534. Unidentified mangrove-derived fungus CRIF2 (order Pleosporales) 8. Unidentified marine fungus M-3 (phylum Ascomycota) 57. Unidentified marine tube worm 768. Unidentified marine-derived bacterium A108 26. Unidentified marine-derived bacterium BH-107 743, 744, 745, 746. Unidentified marine-derived bacterium closely related to Photobacterium alotolerans 383, 384. Unidentified marine-derived bacterium MK-PNG -276A 323, 324, 325, 326. Unidentified marine-derived fungus K063 246. Unidentified mollusc 221, 400, 401. Unidentified mussel 383, 384. Unidentified Pacific Ocean crab 494. Unidentified red alga and marine tube worm 750, 751, 752, 753, 754, 755, 756.

Unidentified shell-less mollusc 196. Unidentified sponge 8, 28, 236, 237, 238, 286, 287, 489. Unidentified sponge (family Dysideidae) 143. Unidentified sponge (order Hadromerida, family Tethyidae) 914. V Verrucosispora maris AB-18-032 121, 122, 123. Verrucosispora sp. 235, 533, 677, 693. Vibrio sp. 177, 178, 744, 747. Vibrio sp. G1363. 747. Vibrio sp. R-10 176. X Xestospongia testudinaria 873. Xestospongia testudinaria [Syn. Aspergillus aculeatus) CRI323-04 873. Z Zoanthus sp. 46. Zygosporium masonii 715.

Index 4 Compound Sampling Geographic Locality Index In this index, all geographic locations in HAMNP Volume 8 have been devided as 16 large areas: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

CHINA JAPAN RUSSIA KOREA WATERS R. O. KOREA ASIA AUSTRALIA OCEANIA EUROPE AFRICA USA NORTH AMERICA CARIBBEAN SEA SOUTH AMERICA PACIFIC OCEAN ANTARCTIC/ARCTIC

For all 175 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” books and a number code sequence of the related compounds follows the detail information immediately. There are 626 related compounds with geographic information in HAMNP Volume 8. 1 CHINA China, Bohai Bay 24, 27. China, Bohai Sea 14. China, China waters 36, 42, 43, 48, 52, 53, 56, 60, 65, 66, 97, 98, 99, 101, 118, 124, 168, 169, 397. China, Chinese sea salt field 1. China, Fujian 21, 22, 23, 37, 40, 41, 862. China, Hainan 34, 110, 285, 374, 375, 376, 1002. China, Pingtan I., Fujian 13, 45. China, Putian Sea Salt Field, Fujian 379, 380. China, Rushan 36, 49, 50. China, Sanya, Hainan 265, 877, 878, 879, 880, 881, 882, 883, 884, 885, 886. China, Weizhou coral reef, Guangxi 864. China, Weizhou I., Guangxi 849. China, Yingkou, Liaoning 54, 72. Hong Kong, Hong Kong 534.

South China Sea, South China Sea 12, 64, 290, 291, 452, 973, 974. Taiwan, Southern Taiwan 1011. 2 JAPAN Japan, Charatsunai beach, Muroran 120, 153. Japan, Japan waters 170, 207, 224, 225, 226, 227, 228, 250, 254, 267, 300, 301, 303, 304, 305, 310, 311, 312, 313, 390, 391, 392, 393, 394, 422, 489, 550, 567, 568, 569, 570, 919. Japan, Nagasaki Shitsu coast 6. Japan, near Nagahama, Kamikoshiki-jima I. 637. Japan, off Amami Tokara Is. 219. Japan, off Shimokoshiki I., Kagoshima 607. Japan, off Shimo-koshiki-jima I., Kagoshima 256. Japan, Shikine-Jima I. 439, 440.

472

Index 4 Compound Sampling Geographic Locality Index

Japan, Suruga Bay 9, 10, 11, 927, 929, 933, 934. Okinawa, Ishigaki I. 124, 442. Okinawa, off Kerama I. 477. Okinawa, Okinawa 28, 181, 246, 293, 318, 360, 405, 406, 407, 446, 447, 448, 449, 450, 478, 531, 532, 686, 689, 744, 747, 913. Okinawa, Seragaki 670, 671, 672, 673, 674. 3 RUSSIA Kuril Is., Kunashir I. 100. 4 KOREA WATERS Korea waters, 35, 487, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 897, 932. 5 R. O. KOREA Ieodo Ieodo Reef 890, 891. Jeju I. Jeju I. 156, 157, 769. 6 ASIA India Chorao I., Goa 17. Indian Ocean 197, 443, 544, 545. Indonesia 293, 418, 419. Indonesia Ambon 277, 278, 279, 280, 281, 282, 284. Indonesia Biak 385. Indonesia Makassar 579. Indonesia Manado 965, 966, 967, 968. Indonesia N. Sulawesi 676, 686, 688. Indonesia off Sulawesi I. 500, 501, 691, 692. Indonisia Sulawesi 630. Malaysia east coast of Malaysia 579. Malaysia Kudat 579. Maldives 272. Philippines Chicoreus nobilis, Cebu 221. Philippines Northwest side of Olango I., Cebu 457. Philippines 59, 259, 260, 261, 331, 332, 333, 389, 421, 458, 459, 972. Red Sea Nabq Mangroves, Gulf of Aqaba 771, 778. Red Sea SS Thistlegorm shipwreck 575, 784, 785. Sea of Japan 998, 999, 1000. Singapore Pulau Hantu Besar 572, 573, 618, 619, 620. Singapore 430, 618, 619. Thailand 2, 8.

Thailand Ton Sai Bay, Phi-Phi I., Krabi province 873. Vietnam Cat Ba I., Haiphong 901, 902, 903. 7 AUSTRALIA Australia 94, 143, 144, 145, 146, 292, 351, 423, 566, 907, 1030. Australia Jamieson Reef, Bonaparte Archipelago 25. Australia Milln Reef, Cape Grafton, Queensland 639, 640, 641. Australia North-western Australia 425, 431, 433. Great Barrier Reef, 453, 971. Queensland Day Reef 190, 191. Queensland Rodda Reef 433. Queensland South Molle I. 850. Queensland Torres Strait 632, 633, 634, 635, 758. Queensland Tydeman Reef 1022, 1023, 1024, 1025. Southern Australia 1010. Western Australia 917, 981. 8 OCEANIA Federated States of Micronesia Chuuk State 981. Federated States of Micronesia Nama I., southeast of Chuuk Lagoon 631, 757, 758, 759. Federated States of Micronesia Pohnpei I. 319, 320, 321, 432, 435, 436, 462, 975. Federated States of Micronesia Truk 360, 363, 364, 365, 366, 367, 368, 369, 370, 387. Federated States of Micronesia Trukese 1003, 1004. Fiji 402, 713, 714, 829. Fiji Great Astrolabe Reef 720. Fiji Korovou Bay 165, 166, 599. Fiji Nasese 601, 602, 603. New Zealand 395, 935, 936, 1006, 1007, 1012, 1014, 1015, 1016. New Zealand Wellington 925, 926. Palau, Oceania 269, 270, 348, 360, 396, 444, 451, 456, 607, 697, 772, 773, 831, 832, 918. Palau, Oceania Big Drop-off 398. Palau, Oceania Mutremdiu Reef 344, 608. Palau, Oceania Ngerderrak Reef 786, 787.

Index 4 Compound Sampling Geographic Locality Index

Palau, Oceania off Short Dropoff, Koror 334, 335, 336, 337. Palau, Oceania Western Caroline I. 1005. Papua New Guinea 159, 160, 192, 193, 294, 343, 387, 388, 492, 493, 546, 547, 561, 563, 564, 648, 649, 709, 710, 711, 712, 790, 968. Papua New Guinea Alotau Bay 565. Papua New Guinea Gallows Reef 791. Papua New Guinea Loloata I. 386. Papua New Guinea Milne Bay 457. Papua New Guinea New Britain I. 496. Papua New Guinea off Milne Bay 690. Papua New Guinea Padana Nahua 834. Papua New Guinea reef wall near Pigeon I. 855. Papua New Guinea Reefs off Loloata I. 323, 324, 325, 326. Papua New Guinea Wewak Bay 708. Solomon Is. 356, 357, 358, 359, 408. Solomon Is. barrier reef of Vangunu I. 353. Solomon Is. Vangunu I. 352, 675. Solomon Is. western coast of Malaita I. 354, 355. Vanuatu 273, 274, 566, 580, 581, 590, 591, 592. 9 EUROPE Guadeloupe I. (Fr.) 543, 663. Mediterranean Sea 4, 490, 668, 669. Norway Kosterfjord, Northern Swedish West coast and Sula Ridge 7, 38. Norway Sula Ridge 7, 38. Norway Trondheim Fjord 798. 10 AFRICA Comoros Is. 269, 270, 271, 361, 362. Comoros Is. Mayotte lagoon 420, 441. Kenya 316. Madagascar 316, 760, 761, 762, 763, 764, 765, 766. Madagascar Salary Bay 681. Mozambique 396. South Africa 454. 11 USA Alaska, USA Chilkat River in Alaska 916. California, USA 907.

473

California, USA Mission Bay, San Diego 296. California, USA Santa Barbara basin, Southern California 177, 178, 179, 180. Florida, USA 626, 792, 811. Florida, USA Broward county, Fort Lauderdale 621, 622, 623. Florida, USA Dry Tortugas National Park 717, 793, 794. Florida, USA Florida Keys 235, 533, 661, 662, 664, 665, 666, 677, 693, 781, 782, 783, 827, 828, 851, 852. Florida, USA Grassy Key and Key Largo 251, 252, 253. Florida, USA Hollywood 195. Florida, USA Port Everglades Inlet, Fort Lauderdale 621, 622, 623, 806. Grenada, USA True Bay 578. Guam, USA 549, 624, 625, 643, 644, 654, 655, 656, 657, 770, 772, 773, 793, 794, 799, 800. Guam, USA Cetti Bay 546, 682, 700, 701, 702, 703, 704, 705, 706. Guam, USA Cocos Lagoon 288, 289. Guam, USA Palmyra 775. Guam, USA Piti Bomb Holes 652, 653, 658. Guam, USA Tumon Bay 799, 800. Hawaii, USA 5, 28, 610, 611, 612, 613, 614, 615, 616, 617, 741. Hawaii, USA Loihi seamount 208, 209, 210, 211, 212, 213. Hawaii, USA off Maui 715. Puerto Rico 317, 717. Puerto Rico Aguadilla 314, 315. Puerto Rico Mona I. 837. Puerto Rico Playa de la Chiva, Vieques I. 707. San Diego, USA San Diego Bay 223. Virgin Is, USA 338, 339. 12 NORTH AMERICA Canada British Columbia 750, 751, 752, 753, 754, 755, 756. Canada Turnagain, British Columbia 399. Mexico Gulf of California 729. Panama 150, 189, 198, 199, 437, 438. Panama Bocas del Toro, Caribbean Sea 172, 173, 174. Panama Coiba National Park 504. Panama Isla Canales de Afuera 700, 701, 702.

474

Index 4 Compound Sampling Geographic Locality Index

13 CARIBBEAN SEA Bahamas Caribbean Sea 403, 404. Bahamas Exuma Is. 553, 554. Bahamas Little San Salvador I. 490, 538, 628, 667. Bahamas Saline lake 872. Bahamas San Salvador Is. 229. Caribbean Sea 31, 31, 171, 539, 541, 543, 563, 564, 629, 928, 930. Curacao I., Caribbean Sea 151, 152, 189, 716. Dominica Rollo Head, Dominica 377, 378. Trinidad 562. Trinidad and Tobago Rusts Bay, Trinidad and Tobago, West Indies 555, 556. 14 SOUTH AMERICA Brazil 679, 680. Brazil Bahia State 74, 75. Brazil off coast of Brazil 484. Chile Quellon, Chiloé I. 494. Venezuela 218.

15 PACIFIC OCEAN Central Pacific Ocean Palmyra Atoll 647. Central Pacific Ocean Strawn I., Palmyra Atoll 856. Central Pacific Ocean tropical Pacific Ocean 383, 384. Marshall Is., Pacific Ocean Enewetak, Marshall Is. 627. New Caledoinia (Fr.) 182, 329, 330, 498, 642, 646, 732, 733, 734, 735, 736, 737, 738, 739, 740. New Caledonia (Fr.) off east coast of New Caledonia 731. New Caledonia (Fr.) off New Caledonia 499. Oahu Kailua beach 743, 744, 745, 746. Pacific Ocean 295, 494. Palmyra Atoll, Central Pacific Ocean 776, 777. 16 ANTARCTIC/ARCTIC Antarctic 239, 240, 241, 242, 243, 244, 870. North Pole near North Pole 340, 341, 342.

Index 5 Compound Pharmacological Activity Index In this index, a set of very formatted pharmacological activity codes have been used, specially for all types of cancer cells, please see “List of Cancer Cells Codes”. A special note is that the word “Cytotoxic” means in vitro anticancer activities, while the word “Antineoplastic” means in vivo anticancer activities. A A new class of sterol binding agents 396. ACAT inhibitor 464. ACE inhibitor 319. Actin polymerisation promoter 789, 579, 794. agr Quorum sensing system inhibitor 383, 384. Algicide 747. Algicide, dinofiagellate Prorocentrum micans 744. Algicide, green alga Chlamydomonas sp. Ev-29 347. Algicide, green alga Chlorella sp. 2-4 347. Algicide, green alga Ulothrix sp. Ev-17 347. Amino-protease inhibitor 219. Amphiphilic siderophore 176, 208, 209, 210, 211, 212, 213. Anthelminthic 858. Anthelmintic 579, 863, 978. Anti-AIDS, against AIDS OI Pathogens 741. Antiarrhythmic 904. Antibacterial 10, 17, 35, 858, 868, 895, 976, 1005, 1010, 1018. Antibacterial inactive, Aeromonas hydrophila subsp. hydrophila ATCC7966 452. Antibacterial inactive, Bacillus subtilis 277, 278, 532, 1012. Antibacterial inactive, Enterococcus durans 563, 564. Antibacterial inactive, Enterococcus faecalis ATCC14506 74, 75. Antibacterial inactive, Escherichia coli 18, 279, 280, 282, 537, 576, 1012. Antibacterial inactive, Escherichia coli ATCC 25922 452. Antibacterial inactive, Escherichia coli ATCCNTCC861 74, 75. Antibacterial inactive, Escherichia coli DH5α 452. Antibacterial inactive, Escherichia coli K-12 C600 R135 898.

Antibacterial inactive, gram-negative bacterium Escherichia coli IAM 12119T 959, 960, 972. Antibacterial inactive, gram-positive bacterium Staphylococcus aureus IAM 12544T 959, 960. Antibacterial inactive, Mycobacterium smegmatis 531, 532. Antibacterial inactive, ORSA 108 74, 75. Antibacterial inactive, Pseudomonas aeruginosa 1012. Antibacterial inactive, Pseudomonas sp. 898. Antibacterial inactive, Staphylococcus aureus 67, 279, 280, 532. Antibacterial inactive, Staphylococcus aureus ATCC 6538 74, 75. Antibacterial inactive, Staphylococcus aureus IAM 12544T 972. Antibacterial inactive, Staphylococcus epidermidis 563, 564. Antibacterial inactive, Staphylococcus lentus 668, 669. Antibacterial inactive, Streptococcus mutans UA159 74, 75. Antibacterial inactive, Streptococcus sanguinis ATCC15300 74, 75. Antibacterial inactive, Streptococcus sobrinus ATCC27607 74, 75. Antibacterial, a range of gram-positive bacteria 798. Antibacterial, Bacillus cereus 658. Antibacterial, Bacillus megaterium 347. Antibacterial, Bacillus subtilis 1, 279, 280, 281, 282, 307, 308, 309, 347, 487, 531, 659, 668, 669, 835, 836, 838, 838, 839, 840, 841, 842, 843, 894, 896, 936, 998, 999, 1000. Antibacterial, Bacillus subtilis ATCC 6633 452. Antibacterial, Bacillus subtilis DSM 10 122. Antibacterial, Bacillus thuringiensis 452.

476

Index 5 Compound Pharmacological Activity Index

Antibacterial, Brevibacillus brevis DSM 30 122. Antibacterial, Enterococcus sp. 234. Antibacterial, Escherichia coli 1, 13, 45, 239, 240, 241, 242, 243, 244, 277, 278, 281, 307, 308, 309, 325, 536, 637, 835, 836, 870. Antibacterial, Escherichia coli ATCC259222 74, 75. Antibacterial, Escherichia coli K-12 C600 R135 899. Antibacterial, gram-negative bacterium Escherichia coli IAM 12119T 918, 931. Antibacterial, gram-positive and -negative bacteria 844, 845, 846, 847, 850, 937, 993, 1029. Antibacterial, gram-positive and -negative bacteria, especially aminoglycosideresistant strains with exception of AAC3-producing organism 898. Antibacterial, gram-positive bacteria 668, 669, 913, 916. Antibacterial, gram-positive bacterium Staphylococcus aureus IAM 12544T 918, 931. Antibacterial, marine bacterium Ruegeria atlantica TUF-D 918, 931, 959, 960, 972. Antibacterial, MDRSA 932. Antibacterial, MDRSP ATCC 700673 494, 495. Antibacterial, Micrococcus luteus 452, 531, 532. Antibacterial, MRSA 245, 323, 324, 325, 326, 551, 552, 851, 852, 932. Antibacterial, MRSAs, three strains 601, 602, 603. Antibacterial, MSSA 851, 852. Antibacterial, Mucor miehei 836, 835. Antibacterial, Mycobacterium bovis, selective, used as a live attenuated vaccine against tuberculosis 14. Antibacterial, Mycobacterium smegmatis 307, 308, 309. Antibacterial, ORSA 8 74, 75. Antibacterial, PRSP 323, 324, 325, 326, 494, 495. Antibacterial, Pseudomonas aeruginosa 243, 307, 308, 309, 380, 838, 838, 839, 840, 841, 842, 843. Antibacterial, Pseudomonas aeruginosa 13 74, 75.

Antibacterial, Pseudomonas aeruginosa ATCC27853 74, 75. Antibacterial, Pseudomonas aeruginosa inactive 658. Antibacterial, Pseudomonas aeruginosa P1 74, 75. Antibacterial, Pseudomonas sp. 899. Antibacterial, Pseudovibrio denitrificans JCM12308, selectively 698, 699. Antibacterial, Pseudovibrio sp. MBIC3368, selectively 698, 699. Antibacterial, Salmonella typhi 838, 838, 839, 840, 841, 842, 843. Antibacterial, Staphylococcus aureus 13, 45, 68, 69, 239, 240, 241, 242, 243, 244, 277, 278, 281, 282, 400, 401, 487, 531, 637, 658, 835, 836, 838, 838, 839, 840, 841, 842, 843, 870. Antibacterial, Staphylococcus aureus ATCC 29213 452. Antibacterial, Staphylococcus aureus ATCC259223 74, 75. Antibacterial, Staphylococcus aureus DSM 20231 122. Antibacterial, Staphylococcus epidermidis 864, 870, 908, 909. Antibacterial, Staphylococcus pyrogenes 827, 828. Antibacterial, Streptococcus mutans clinical isolate 2.M7/4 74, 75. Antibacterial, Streptococcus pneumonia 827, 828. Antibacterial, Streptococcus pneumoniae ATCC 6303 494, 495. Antibacterial, Streptococcus pyogenes 494, 495. Antibacterial, Streptomyces viridochromogenes Tü 57 836, 835. Antibacterial, VREF 245, 323, 324, 325, 326, 798. Antibiotic 31, 329, 340, 341, 342, 465, 466, 467, 468, 829, 991, 996, 1019, 1020, 1028. Antibiotic, green alga Dunaliella sp. 553, 554. Anticancer-Cell-Effect 150, 230, 230, 230, 230, 231, 251, 252, 492, 504, 505, 505, 545, 605, 606, 621, 622, 623, 624, 626, 636, 647, 660, 678, 694, 695, 696, 716, 716, 717, 748, 770, 770, 789, 790, 791, 799,

Index 5 Compound Pharmacological Activity Index

800, 807, 808, 809, 810, 811, 812, 813, 819, 833, 793, 793, 196, 196, 196, 196, 579, 794, 181, 181. Anticyanobacterial, Nostoc Ev-1 347. Anti-fibrosis, inhibits proliferation of WI26, blocks adhesion of THP-1 to a monolayer of WI26, and reduces contractile capacity of WI26 cells in three-dimensional free-floating collagen gels 862. Antifoulant, bryozoan Bugula neritina larval settlement 12, 61, 64. Antifoulant, inhibits Bugula neritina larvae settlement 265. Antifungal 30, 47, 59, 101, 330, 389, 396, 403, 404, 789, 849, 913, 969, 979, 980, 1031. Antifungal inactive, Aspergillus niger 531. Antifungal inactive, Candida albicans 279, 282, 337. Antifungal inactive, Candida albicans ATCC 36801 serum type A 74, 75. Antifungal inactive, Candida albirnns 1012. Antifungal inactive, Cladzspwum resina 1012. Antifungal inactive, Mucor hiemalis IAM 6088 959. Antifungal inactive, Saccharomyces cerevisiae 741. Antifungal inactive, Saccharomyces cerevisiae IAM 1438T 959, 960, 972. Antifungal inactive, Trichophyton mtagropbytes 1012. Antifungal, ABRCA 690. Antifungal, Aspergillus niger 6, 532. Antifungal, Aspergillus oryzae 741. Antifungal, Botrytis cinera 838, 838, 839, 840, 841, 842, 843. Antifungal, Botrytis cinerea 845, 846, 847. Antifungal, Candida albicans 1, 182, 187, 188, 259, 260, 261, 277, 278, 280, 281, 331, 332, 333, 334, 335, 336, 349, 350, 379, 380, 396, 498, 741, 794, 836, 936, 937, 971, 997, 998, 999, 1000. Antifungal, Candida albicans ATCC 24433 183, 184, 185, 186. Antifungal, Candida albicans wild type 690. Antifungal, Candida albicans wild type and ABRCA strains 690, 691, 692. Antifungal, Candida spp. 22 samples 730. Antifungal, Colletotrichum acutatum 838, 838, 839, 840, 841, 842, 843, 845, 846, 847.

477

Antifungal, Cryptococcus neoformansisolates 7 samples 730. Antifungal, Cundidu albicuns 579. Antifungal, fungi growth inhibitor 642. Antifungal, Gaeumannomyces graminis 67, 69, 70. Antifungal, Helmintbosporium gramineum 642. Antifungal, Mortierella ramanniana 254, 567, 568, 569, 570. Antifungal, Mortierella rumunniunus 307, 308, 309. Antifungal, Mucor hiemalis IAM 6088 918, 931, 960, 972. Antifungal, pathogenic fungi 845, 846, 847. Antifungal, pathogenic fungus Botrytis cinerea 844. Antifungal, pathogenic fungus Colletotrichum acutatum 844. Antifungal, pathogenic fungus Rhizoctonia solani 844. Antifungal, Penicillium notatum 741. Antifungal, phytopathogenic fungus Alternaria solani 239, 240, 241, 242, 243, 244. Antifungal, phytopathogenic fungus Pyricularai oryzae 239, 240, 241, 242, 243, 244. Antifungal, Phytophthora sp. 636. Antifungal, Piricularia oryzae 642. Antifungal, plant pathogenic fungi 627. Antifungal, promising candidates for development of non-cytotoxic antifungal agents 844, 845, 846, 847. Antifungal, Pyricularia oryzae, strong and selective 57. Antifungal, Rhizoctonia solani 838, 838, 839, 840, 841, 842, 843, 845, 846, 847. Antifungal, Rhodotorula glutinis 349, 350. Antifungal, Saccharomyces cerevisiae 347, 349, 350. Antifungal, Saccharomyces cerevisiae IAM 1438T 918, 931, 960. Antifungal, Saccharomyces cerevisiae, baker’s yeast 190, 191. Antifungal, Saccharomyces pastorianus 645. Antifungal, selective 515. Antifungal, Trichophyton mentagrophytes 531, 532, 741. Anti-HIV 630.

478

Index 5 Compound Pharmacological Activity Index

Anti-HIV, HIV-1 691, 692. Anti-HIV, HIV-1 fusion assay, LAV T-cell tropic viral strain 631, 758, 759. Anti-HIV, HIV-1 integrase inhibitor 444, 451. Anti-HIV, HIV-1 neutralization assay, host cell TZM-bl cell line 631, 758, 759. Anti-HIV, HIV-1 neutralization assay, host cell TZM-bl cell line, HXB2 T-cell tropic viral strain 631, 758, 759. Anti-HIV, HIV-1 neutralization assay, YU2-V3 viral strain 758, 632, 633, 634, 635. Anti-HIV, HIV-1 neutralization assay, YU2-V3 viral strain, focus on extensive studies to define its mode of action 648. Anti-HIV, inhibits infection of hmn T-lymphoblastoid cells by HIV-1RF 648, 649. Anti-HIV, protects cells infected by HIV virus 498. Anti-HIV, SF162 macrophage-tropic viral strain 631, 758, 759. Anti-HIV, single round HIV-1 neutralization assay, SF162 strain 608, 609. Anti-HIV-1 638. Anti-HIV-1, HIV-1 SF162 envelope 691, 500. Anti-HIV-1, neutralized HIV-1 691, 692, 500. Anti-HIV-2, mink lung cells HIV-2 741. Anti-HIVs, PBMC cells infected by HIV-1 III B strain 731. Anti-inflammatory 148, 356, 357, 358, 359, 408, 664, 665, 666, 675, 718, 788, 827, 828, 859, 860, 893, 907, 914. Anti-inflammatory and chemoprevention 719. Anti-inflammatory, hmn antipsoriatic effects, PHK 354, 355. Anti-inflammatory, hmn antipsoriatic effects, PHK, inhibits release of both TNFa and IL-8 344. Anti-inflammatory, hmn antipsoriatic effects, PHK, too cytotoxic 353. Anti-inflammatory, hmn neutrophil free radical inhibition, MMOA: - superoxide anion inhibition 1006, 1007. Anti-inflammatory, hmn non-pancreatic phospholipase A2 inhibitor 418. Anti-inflammatory, in vitro and in vivo, mouse ear edema assay, may be a potential drug candidate 296. Anti-inflammatory, in vivo, mouse paw edema model 353.

Anti-inflammatory, in vivo, mouse paw edema model, nearly 100 times more potent than current NSAIDs naproxen 344. Anti-inflammatory, inhibits release of IL-8 354. Anti-inflammatory, mouse oedema model, lacking cytotoxicity 352. Anti-inflammatory, NO assay, RAW264.7 cells, with little or no cytotoxicity 875. Anti-inflammatory, via inhibition of NF-κB luciferase and nitrite production 5. Antileishmanial, Leishmania donovani 172, 173, 174, 200. Antileishmanial, Leishmania mexicana 853, 854. Antimalarial 197, 837. Antimalarial, Plasmodium falciparum D6 889. Antimalarial, Plasmodium falciparum W2 889. Anti-MDR, vinblastine-resistant CCRF-CEM hmn leukemic lymphoblasts 432, 435, 436, 462. Antimicroalgal 553, 554. Antimicroalgal, Chlorella sorokiniana 836. Antimicroalgal, Chlorella vulgaris 836. Antimicroalgal, Pythium ultimum 836. Antimicroalgal, Rhizoctonia solani 836. Antimicrobial 223, 268, 306, 311, 312, 313, 750, 751, 752, 753, 754, 755, 756, 877, 878, 879, 880, 881, 882, 883, 884, 885, 886, 892, 969, 970, 992. Antimicrobial, broad spectrum 890, 891. Antimitotic 150, 196, 515, 529. Antimycobacterial, Mycobacterium aviumintracellulare 749, 768. Antimycobacterial, Mycobacterium bovis, against both actively growing and dormant states 236, 237, 238. Antimycobacterial, Mycobacterium smegmatis, against both actively growing and dormant states 236, 237, 238. Antimycobacterial, Mycobacterium tuberculosis, against both actively growing and dormant states 236, 237, 238. Antineoplastic, in vivo 170, 275, 460, 577, 793. Antineoplastic, in vivo, a colon tumor 770. Antineoplastic, in vivo, a mammary tumor 770. Antineoplastic, in vivo, B16 196, 540. Antineoplastic, in vivo, entered a clinical trial but produced only marginal activity 529. Antineoplastic, in vivo, ICR mouse S180 938, 940.

Index 5 Compound Pharmacological Activity Index

Antineoplastic, in vivo, L1210 540. Antineoplastic, in vivo, P388 540. Antineoplastic, in vivo, phase II clin. Trial, 2002, granted orphan drug status by FDA, 2004, for treatment of acute lymphoblastic leukaemia and multiple myeloma 490. Antineoplastic, in vivo, Phase II clin. trial, 2004 741. Antineoplastic, in vivo, phase II clinical, lacked clinically significant activity 196, 196. Antineoplastic, in vivo, PS 230, 545, 196. Antineoplastic, in vivo, therapeutic studies, HCT116 bearing SCID mice demonstrated efficacy 535. Antiosteoporosis, Cathepsin B model 219. Antioxidant 868, 873. Antioxidant inactive, DPPH radical scavenger 115, 116, 117. Antioxidant, DPPH radical scavenger 15, 51, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114. Antioxidant, free radical scavenger, to protect N18-RE-105 cells against L-glutamate toxicity 124. Antioxidant, oxygen radical absorbance 861. Antioxidant, radical DPPH scavenger 20. Antiplasmodial 970. Antiplasmodial, DRPF Dd2 1022, 1023, 1024, 1025. Antiplasmodial, DSPF 3D7 1022, 1023, 1024, 1025. Antiplasmodial, DSPF, extremely potent 850. Antiplasmodial, HEK-293 1022, 1023, 1024, 1025. Antiplasmodial, MDRPF, extremely potent 850. Antiplasmodial, Plasmodium falciparum 198, 437, 438, 618, 619, 620, 853, 854. Antiplasmodial, Plasmodium falciparum W2 189, 199. Antiproliferative 189, 439, 440, 792. Antiproliferative, HTCLs 151, 152. Antispasmodic 1005. Antiswarming, gram-negative bacterium Pseudomonas aeruginosa PA01 618, 619, 620. Antitrypanosomal, Trypanosoma cruzi 853, 854.

479

Antituberculosis 14. Antituberculosis, inoculum Mycobacterium tuberculosis 652, 653, 654, 655, 656, 657. Antituberculosis, MABA assay, avirulent strain Mycobacterium tuberculosis H37Ra 327, 328. Antituberculosis, Mycobacterium tuberculosis 474, 475, 658, 749, 768. Antituberculosis, Mycobacterium tuberculosis H37Rv 604, 741. Antitussive 893. Antiviral 296, 757, 893, 932, 1013. Antiviral, HSV-1 inhibitor, direct inactivation 202, 203, 204, 205, 206. Antiviral, HSV-2 inhibitor, direct inactivation 202, 203, 204, 205, 206. Antiviral, influenza A H1N1 3, 266. Antiviral, influenza A H3N2 266. Antiviral, influenza A/WSN/33 virus 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93. Antiviral, inhibits growth of both RNA and DNA viruses 541. Antiviral, inhibits growth of DNA viruses, HSV-1 538. Antiviral, inhibits growth of DNA viruses, HSV-2 538. Antiviral, inhibits growth of RNA and DNA viruses 540. Antiviral, inhibits growth of RNA viruses, coxsackie virus 538. Antiviral, inhibits growth of RNA viruses, equine rhinovirus 538. Antiviral, mink lung cell HSV-2 741. Antiviral, poxvirus Molluscum contagiosum virus MCV 667. Anxiolytic 904. Aspartic proteases inhibitor, Aspartic proteases inhibitor, protease cathepsin D 252. Aspartic proteases inhibitor, protease ADAM9 251, 252, 253. Aspartic proteases inhibitor, protease ADAM10 251, 252, 253. Aspartic proteases inhibitor, protease cathepsin D 251, 253. Aspartic proteases inhibitor, protease cathepsin E 251, 252, 253.

480

Index 5 Compound Pharmacological Activity Index

Aspartic proteases inhibitor, protease TACE 251, 252, 253. Atropine antagonist 162. B Binds to DNA high affinity bisintercalation 693. Bioassay-guided fractionation with anti-fungal activity 637. Blood pigment which selectively accumulates Vanadium 125. C Ca2+ oscillation inhibitor 790, 791. Ca2+ oscillations inhibitor, neocortical neurons 887, 888. Ca2+ oscillations inhibitor, neocortical neurons, nearly complete inhibition 875. Calcium ATPase inhibitor 476. Calmodulin antagonist 478. Carboxypeptidase A inhibitor 469, 470, 471, 472, 473. Cardiac depressant 904. Cardioactive 486, 904, 914. Cardioactive, coronary vasodilatory and asystolic agent 905. Cardiotonic 485. Cathepsin B inhibitor 170. Caused multinuclei formation in cells 670, 671, 672, 673, 674. Cell cycle inhibitor, mammalian 60, 95, 96, 124, 124. Cell cycle inhibitor, mammalian, tsFT210, caused complete arrest in G2/M phase 102, 103. Cell cycle progression inhibitor 118. Cell death inducer, HT1080, under endoplasmic reticulum stress 250. Cell growth inhibitor 195, 369, 370, 579. Cell growth inhibitor, Microcystis aeruginosa 167. Cell growth Inhibitor, PS 803. Cell inhibitor 848. Cell proliferation inhibitor 499, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968. Cellular microfilament disrupter 624. Cerebroprotective 148. Chemoprevention 718. Chymotrypsin inhibitor 810, 483, 801, 802, 820, 821, 822, 823, 824, 805.

Chymotrypsin inhibitor, strong 804. CNS depressant 914. CNS system depressant 412. Colony formation inhibitor 972. COMPARE analises 953. COMPARE analyses were positive 546. Contractile activity, gpg ileum 910, 911. Cysteine protease inhibitor 219. Cytokinesis inhibitor 624. cytoprotective agent, infection production inhibitor 731. Cytotoxic 47, 268, 271, 283, 311, 312, 313, 317, 318, 363, 364, 442, 445, 454, 461, 503, 547, 649, 720, 913, 925, 926, 1003, 1004. Cytotoxic and antineoplastic, in vitro and in vivo, NCI-H69, NCI-H82, NCI-H446 and NCI-H510 196. Cytotoxic inactive, A549 21, 22, 23, 41, 43, 97, 98, 115, 116, 117, 156, 897. Cytotoxic inactive, ACHN 838, 839, 839, 841, 842, 843. Cytotoxic inactive, Bel7402 21, 22, 23, 41, 97, 99, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117. Cytotoxic inactive, C38 and M16 793. Cytotoxic inactive, CHO-K1 25. Cytotoxic inactive, cultured RAW cells 718, 719. Cytotoxic inactive, CX1 294. Cytotoxic inactive, H460 25. Cytotoxic inactive, HCT15 838, 839, 839. Cytotoxic inactive, HCT116 421, 501, 609, 658, 872, 985. Cytotoxic inactive, HEK-293 360. Cytotoxic inactive, HeLa 62, 546, 682, 705. Cytotoxic inactive, HL60 21, 22, 23, 24, 27, 41, 43, 97, 98, 115, 116, 117. Cytotoxic inactive, hmn colon tumour cells 430. Cytotoxic inactive, HT29 25, 288, 546, 655, 656, 657, 682, 705. Cytotoxic inactive, HT29 Colon adenocarcinoma GR-III 347. Cytotoxic inactive, J774.A1 360. Cytotoxic inactive, K562 295. Cytotoxic inactive, KB 455, 741. Cytotoxic inactive, L1210 62, 294.

Index 5 Compound Pharmacological Activity Index

Cytotoxic inactive, MCF7 25, 201, 288, 289, 586, 591, 654, 655, 656, 657, 658. Cytotoxic inactive, MDA-MB-231 838, 839, 839. Cytotoxic inactive, NCI-H23 838, 839. Cytotoxic inactive, NCI-H460 39. Cytotoxic inactive, neuro-2a 575, 791. Cytotoxic inactive, NUGC-3 838, 839, 839. Cytotoxic inactive, P388 37, 41, 115, 116, 117, 1012, 1014, 1015, 1016. Cytotoxic inactive, P388 synthetic sample 361. Cytotoxic inactive, panel of NCI’s 60 tumour cell lines 427, 667. Cytotoxic inactive, PC3 838, 839, 839. Cytotoxic inactive, RBL-2H3 1008, 1009. Cytotoxic inactive, SF268 25. Cytotoxic inactive, SK-MEL-2 897. Cytotoxic inactive, SK-OV-3 156. Cytotoxic inactive, SMMC-7721 34. Cytotoxic inactive, T47D 36, 50. Cytotoxic inactive, UT7 681. Cytotoxic inactive, WEHI-164 360. Cytotoxic, 3Y1 976, 986, 987, 988. Cytotoxic, 786-0 580, 579, 583. Cytotoxic, A-10 612. Cytotoxic, A2780 457. Cytotoxic, A375-S2 36, 48, 397. Cytotoxic, A498 158, 159, 161, 165, 269, 270, 347, 365, 377, 378, 562, 579, 582, 587, 590, 595, 597, 599, 627. Cytotoxic, A549 37, 52, 53, 56, 58, 60, 65, 66, 71, 99, 124, 128, 157, 168, 169, 199, 201, 215, 235, 343, 371, 420, 441, 453, 533, 545, 620, 659, 677, 693, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 743, 744, 745, 746, 760, 761, 762, 763, 764, 765, 766, 792. Cytotoxic, ACHN 840. Cytotoxic, AGS 121, 122, 123. Cytotoxic, Antiviral/Cytotoxicity assay, BSC-1 1015. Cytotoxic, B16 541. Cytotoxic, BC 779. Cytotoxic, Bel7402 37, 52, 53, 66, 98. Cytotoxic, BGC823, 100μg/mL 1031. Cytotoxic, BT549 377, 378. Cytotoxic, BXF-1218L 835. Cytotoxic, BXF-T24 835. Cytotoxic, BXPC3 272, 494.

481

Cytotoxic, C6 1008, 1009. Cytotoxic, CA46 789, 794. Cytotoxic, CCRF-CEM 194, 214, 917. Cytotoxic, cell cycle analysis in A2780 cells, treated by 1.3μmol/L scleritodermin A for 24h, a G2/M block yielded 457. Cytotoxic, cell division inhibitor 912. Cytotoxic, cell invasion assay 769. Cytotoxic, CEM 347, 433. Cytotoxic, CEM-TART 690. Cytotoxic, CNXF-498NL 835. Cytotoxic, CNXF-SF268 835. Cytotoxic, Colon26 502, 574. Cytotoxic, Colon205 158, 159, 161, 201, 667. Cytotoxic, Corbett assay, no selective cytotoxic 426, 427, 427, 428, 428, 434, 455. Cytotoxic, CV-1 128, 453, 741. Cytotoxic, CXF-HCT116 835. Cytotoxic, CXF-HT29 835. Cytotoxic, developing eggs of sea urchin Strongylocentrotus intermedius 497. Cytotoxic, DMS273 505. Cytotoxic, DU145 163, 165, 196, 272, 377, 378, 494, 495, 579, 582, 587, 590, 595, 597, 599, 921, 922, 923, 924. Cytotoxic, EPC 731, 732, 733, 734, 735, 736, 737, 738, 739, 740. Cytotoxic, GXF-251L 835. Cytotoxic, H125 247, 248, 249, 250. Cytotoxic, H460 201, 316, 347, 492, 493, 535, 647, 678, 700, 707, 774, 776, 777, 790, 791, 875. Cytotoxic, HCT8 58, 620. Cytotoxic, HCT15 156, 157, 579, 580, 583, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 840, 897. Cytotoxic, HCT116 71, 119, 150, 163, 164, 165, 166, 259, 260, 261, 334, 335, 336, 337, 338, 339, 340, 341, 342, 381, 382, 413, 414, 415, 416, 417, 457, 500, 500, 535, 538, 540, 579, 579, 580, 582, 583, 587, 590, 593, 594, 595, 597, 598, 599, 600, 607, 628, 648, 661, 662, 667, 690, 691, 691, 692, 729, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 757, 770, 776, 792, 856, 917, 928, 930, 981, 982, 983, 984. Cytotoxic, HCT116, damages DNA 997.

482

Index 5 Compound Pharmacological Activity Index

Cytotoxic, HCT116, mixture of apratoxins F and G 777. Cytotoxic, HCT116/VM46 multidrug-resistant colon tumour 457. Cytotoxic, HEK-293 578. Cytotoxic, HeLa 119, 278, 281, 282, 489, 700, 701, 702, 703, 704, 706, 770, 775, 781, 782, 783, 784, 785, 848, 921, 922, 923, 924, 976, 986, 987, 988. Cytotoxic, HeLa, 100μg/mL 1031. Cytotoxic, HeLa, inhibits cell migration at subinhibitory concentrations 385. Cytotoxic, HeLa-S3 181, 222, 422, 491, 548, 549, 550, 643. Cytotoxic, hemocytometer counting assay 776, 777. Cytotoxic, HepG2 121, 122, 123, 423, 452, 676, 686, 688, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 921, 922, 923, 924, 973, 974. Cytotoxic, HEY 343, 561. Cytotoxic, HL60 36, 37, 49, 50, 52, 53, 56, 60, 63, 66, 71, 99, 119, 243, 380, 504. Cytotoxic, HL60 resistant 732, 733, 734, 735, 736, 737, 738, 739, 740. Cytotoxic, HL60, 100μg/mL 1031. Cytotoxic, HL60, antiproliferative 731, 732, 733, 734, 735, 736, 737, 738, 739, 740. Cytotoxic, HM02 423. Cytotoxic, hmn colon tumour cell lines 458, 459. Cytotoxic, hmn lymphoblastic leukemia cell lines 663. Cytotoxic, hmn tumour cell lines 231, 770. Cytotoxic, HNXF-536L 835. Cytotoxic, HOP-62 579, 580, 583. Cytotoxic, HOP-92 562. Cytotoxic, Hs578T 562. Cytotoxic, HT29 128, 195, 199, 215, 289, 371, 420, 441, 453, 489, 579, 581, 582, 583, 585, 588, 590, 592, 652, 653, 654, 700, 701, 702, 703, 704, 706, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 743, 744, 745, 746, 760, 761, 762, 763, 764, 765, 766, 770, 775, 781, 782, 783. Cytotoxic, HTCLs cells 290, 291. Cytotoxic, Huh7 423. Cytotoxic, IC-2WT 201.

Cytotoxic, IGROV1 163, 165, 579, 582, 587, 590, 595, 597, 599. Cytotoxic, IMR-32 195. Cytotoxic, in vitro and in vivo 192. Cytotoxic, in vitro and in vivo, A549 193. Cytotoxic, in vitro and in vivo, HEY 193, 160, 159. Cytotoxic, in vitro and in vivo, LoVo 193. Cytotoxic, in vitro and in vivo, MCF7 193, 160. Cytotoxic, in vitro and in vivo, P388 193, 160. Cytotoxic, in vitro and in vivo, U373 193, 159. Cytotoxic, infected PBMC cells 731. Cytotoxic, inhibits growth of several tumour cell lines, including panc89, HT29 and Colo357 668, 669. Cytotoxic, JurKat 1026, 1027. Cytotoxic, JurKat-T 834. Cytotoxic, K562 29, 30, 32, 33, 63, 71, 119, 201, 681, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740. Cytotoxic, K562, 100μg/mL 1031. Cytotoxic, KB 230, 232, 233, 348, 405, 406, 407, 426, 427, 428, 433, 434, 446, 450, 477, 499, 505, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 530, 625, 644, 697, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 770, 772, 773, 779, 780, 789, 793, 794, 795, 796, 797, 831, 832. Cytotoxic, KM20L2 269, 270, 272, 365, 494, 495, 546, 627. Cytotoxic, L1210 297, 405, 406, 407, 424, 425, 426, 427, 428, 433, 446, 450, 477, 531, 532, 541, 555, 556, 557, 558, 559, 560, 686, 894, 896, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968. Cytotoxic, L1210, exceptionally 693. Cytotoxic, L5178Y 277, 278, 279, 280, 281, 282, 284, 285, 374, 375, 376, 595, 596, 870, 1002. Cytotoxic, LNCaP 377, 378, 489. Cytotoxic, LoVo 230, 232, 343, 505, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 530, 625, 644, 652, 653, 741, 770, 772, 773, 780, 793, 794, 795, 797. Cytotoxic, LOX 158, 161, 201.

Index 5 Compound Pharmacological Activity Index

Cytotoxic, LOX-IMVI 163, 165, 504, 579, 582, 587, 590, 595, 597, 599. Cytotoxic, lung and colon tumour cells 151, 152. Cytotoxic, lung and stomach tumour cells 891. Cytotoxic, LXF-1121L 835. Cytotoxic, LXF-289L 835. Cytotoxic, LXF-526L 835. Cytotoxic, LXF-529L 835. Cytotoxic, LXF-629L 835. Cytotoxic, LXF-H460 835. Cytotoxic, M14 579, 580, 583. Cytotoxic, M17 505. Cytotoxic, M17-Adr 294. Cytotoxic, MALME-3M 201. Cytotoxic, marginal cell proliferation inhibition 20. Cytotoxic, MAXF-401 667. Cytotoxic, MAXF-401NL 835. Cytotoxic, MAXF-MCF7 835. Cytotoxic, MCF7 121, 122, 123, 272, 327, 327, 328, 328, 343, 377, 378, 452, 494, 495, 534, 546, 571, 572, 573, 579, 580, 581, 582, 583, 583, 584, 585, 587, 588, 589, 590, 592, 593, 594, 598, 652, 653, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 742, 743, 744, 745, 746, 917, 921, 922, 923, 924, 973, 974. Cytotoxic, MCF7 resistant 732, 733, 734, 735, 736, 737, 738, 739, 740. Cytotoxic, MDA231 377, 378, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740. Cytotoxic, MDA361 377, 378. Cytotoxic, MDA435 377, 378, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740. Cytotoxic, MDA468 377, 378. Cytotoxic, MDA-MB-231 163, 165, 371, 504, 579, 582, 587, 590, 595, 597, 599, 600, 760, 761, 762, 763, 764, 765, 766, 840. Cytotoxic, MDA-MB-231 166. Cytotoxic, MDA-MB-231, growth inhibition 792. Cytotoxic, MDA-MB-231/ATCC 562. Cytotoxic, MDA-MB-435 158, 161, 230, 535, 546, 612, 917. Cytotoxic, MDA-N 546, 917. Cytotoxic, ME180 316. Cytotoxic, MEL28 199, 215, 420, 441. Cytotoxic, MEXF-276L 835. Cytotoxic, MEXF-394NL 835.

483

Cytotoxic, MEXF-462NL 835. Cytotoxic, MEXF-514L 835. Cytotoxic, MEXF-520L 835. Cytotoxic, MGC-803 71. Cytotoxic, MiaPaCa 731, 732, 733, 734, 735, 736, 737, 738, 739, 740. Cytotoxic, microtubule formation inhibitor 158. Cytotoxic, Molt4 52, 53, 66, 97, 98, 99, 201, 266, 571, 572, 573. Cytotoxic, MRC-5 731, 732, 733, 734, 735, 736, 737, 738, 739, 740. Cytotoxic, NBT-T2 (BRC-1370) 670, 671, 672, 673, 674. Cytotoxic, NCI’s developmental therapeutics program 583. Cytotoxic, NCI-ADR 230. Cytotoxic, NCI-H23 839, 840. Cytotoxic, NCI-H187 779, 789. Cytotoxic, NCI-H460 158, 159, 161, 269, 270, 272, 365, 452, 494, 495, 504, 546, 627, 709, 710, 711, 712, 771, 921, 922, 923, 924, 973, 974. Cytotoxic, NCI-H460, much more potent than apratoxin A sulfoxide 778. Cytotoxic, NCI-H522 163, 165, 315, 579, 582, 587, 590, 595, 597, 599. Cytotoxic, neuro-2a 492, 493, 496, 535, 565, 709, 710, 711, 712, 784, 785, 790. Cytotoxic, neuroblastoma cells 563, 564. Cytotoxic, NIH3T3, growth inhibition 792. Cytotoxic, NMuMG, growth inhibition 792. Cytotoxic, no selective 426. Cytotoxic, NSCLC-N6 273, 274, 499, 566, 580, 581. Cytotoxic, NUGC-3 840. Cytotoxic, number of tumour cells, including several drug-resistant cell lines 498. Cytotoxic, OVCAR-3 158, 159, 161, 201, 269, 270, 365, 377, 378, 579, 580, 583, 627. Cytotoxic, OVCAR-4 562. Cytotoxic, OVCAR-8 731, 732, 733, 734, 735, 736, 737, 738, 739, 740. Cytotoxic, OVXF-899L 835. Cytotoxic, OVXF-1619L 835. Cytotoxic, OVXF-OVCAR3 835. Cytotoxic, P388 9, 10, 11, 21, 22, 23, 128, 154, 155, 171, 197, 207, 207, 215, 256, 272, 293, 310, 319, 320, 321, 322, 343, 346, 360, 362, 365, 366, 367, 368, 369, 370, 387,

484

Index 5 Compound Pharmacological Activity Index

388, 390, 391, 392, 393, 394, 395, 443, 453, 490, 494, 495, 499, 502, 538, 539, 540, 541, 542, 543, 544, 567, 568, 569, 574, 579, 607, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 646, 741, 916, 927, 929, 933, 934, 935, 936, 938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 958, 976, 986, 987, 988, 1021. Cytotoxic, P388 natural sample 361. Cytotoxic, P388, significant 957. Cytotoxic, pancreatic carcinoma 679. Cytotoxic, panel of 14 hmn tumour cell lines, GI50 is in order of 1.0×10‒8mol/L 489. Cytotoxic, panel of 36 tumour cell lines, mean IC50 = 0.130μg/mL, mean IC70 = 0.210μg/mL 835. Cytotoxic, panel of 39 hmn tumour cell lines 181. Cytotoxic, panel of 39 hmn tumour cell lines, mean Log10 GI50 mol/L = –5.25 953. Cytotoxic, panel of cell lines, including hmn tumourVero cell 731. Cytotoxic, panel of hmn tumour cell lines 296, 648. Cytotoxic, panel of hmn tumour cell lines, GI50 = 0.75~3.4μg/mL 1021. Cytotoxic, panel of hmn tumours HTCLs, potent 989, 990. Cytotoxic, panel of NCI’s 60 cell lines, selected 163, 165, 579, 579, 580, 582, 587, 590, 595, 597, 599. Cytotoxic, panel of NCI’s 60 cell screen testing, selected 583. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, average IC50 = 13μmol/L 431. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, mean GI50 = 2.5×10‒7mol/L 546. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, mean GI50 = 2.3 nmol/L 680. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, mean IC50 = 3μmol/L 433. Cytotoxic, panel of NCI’s 60 hmn tumour cell lines, median GI50= 9.1μmol/L 715. Cytotoxic, panel of NCI’s 60 tumour cell lines 338, 339, 504. Cytotoxic, panel of NCI’s 60 tumour cell lines, high level of cytotoxicity, particularly for

leukemia, renal, and prostate tumour cell lines 492. Cytotoxic, panel of NCI’s cell lines, GI50= 8.3μmol/L 629. Cytotoxic, panel of NCI’s Development Therapeutics Program 593, 594, 598. Cytotoxic, panel of NCI’s Developmental Therapeutics Program 579, 580. Cytotoxic, panel of NCIs one-dose 60-cell-line 314, 315. Cytotoxic, panel of tumour cell lines, IC50 = 2.1~24.4 nmol/L 620. Cytotoxic, PAXF-1657L 835. Cytotoxic, PAXF-PANC1 835. Cytotoxic, PC3 377, 378, 620, 731, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 840. Cytotoxic, PC3MM2 377, 378. Cytotoxic, PC12 278, 281, 282. Cytotoxic, potent and non-selective 639, 640, 641. Cytotoxic, PRXF-22RV1 835. Cytotoxic, PRXF-DU145 835. Cytotoxic, PRXF-LNCAP 835. Cytotoxic, PRXF-PC3M 835. Cytotoxic, PS (=P388) 443, 728. Cytotoxic, PTEN-deficient MDA-MB-468 972. Cytotoxic, PV4 cultured cells transformed with virus Polyoma sp. 409. Cytotoxic, PXF-1752L 835. Cytotoxic, reh lymphoblastic leukemia 196. Cytotoxic, resistant HL60 731. Cytotoxic, resistant MCF7 731. Cytotoxic, RPMI8226 579, 580, 583. Cytotoxic, RXF-1781L 835. Cytotoxic, RXF-393, high selective 715. Cytotoxic, RXF-393NL 835. Cytotoxic, RXF-486L 835. Cytotoxic, RXF-944L 835. Cytotoxic, selective 433. Cytotoxic, several cell lines 154, 155. Cytotoxic, several hmn lymphoma cell lines 196. Cytotoxic, several tumour cell lines, weak 292. Cytotoxic, SF268 272, 452, 494, 495, 562, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 973, 974. Cytotoxic, SF268, high selective 715. Cytotoxic, SF295 269, 270, 365, 546, 627. Cytotoxic, SF539 158, 159, 161, 579, 580, 583.

Index 5 Compound Pharmacological Activity Index

Cytotoxic, SGC7901 921, 922, 923, 924. Cytotoxic, SKBR3 327, 327, 328, 328, 347, 457, 489. Cytotoxic, SK-MEL-2 156, 157, 667. Cytotoxic, SK-MEL-5 269, 270, 546, 627. Cytotoxic, SK-MEL-28 347. Cytotoxic, SK-MEL-S 365. Cytotoxic, SK-OV-3 157, 347, 377, 378, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 530, 612, 620, 731, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 897. Cytotoxic, SNB19 201. Cytotoxic, SNB75 504. Cytotoxic, SR 314. Cytotoxic, starfish eggs 912. Cytotoxic, SW480 921, 922. Cytotoxic, SW1990 921, 922, 923, 924. Cytotoxic, T24 410, 411. Cytotoxic, T24 tumour cells, incorporation of [methyl-3H] thymidine 429. Cytotoxic, T47D 49. Cytotoxic, U251 163, 165, 347, 579, 582, 587, 590, 595, 597, 599, 921, 922, 923, 924. Cytotoxic, U2OS 661, 662, 770, 775. Cytotoxic, U2OS, growth inhibition 792. Cytotoxic, U373 561. Cytotoxic, U373MG 343. Cytotoxic, U-87-MG 377. Cytotoxic, U937 36, 49, 50, 54, 55, 72, 266. Cytotoxic, uninfected PBMC cells 731. Cytotoxic, UO-31 314, 315, 562. Cytotoxic, UXF-1138L 835. Cytotoxic, V79 918, 931, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968, 972. Cytotoxic, various cell lines 8. Cytotoxic, Vero 173, 174, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740. Cytotoxic, weak 402, 447, 448, 449, 874. Cytotoxic, WHCO1 316. Cytotoxic, WHCO6 316. Cytotoxic, XF498 156, 157, 897. Cytotoxin 678, 1001. D Disruptor of cellular microfilament network, normal fibroblasts 793. DNA polymerase inhibitor 894.

485

E Elastase inducer 652, 653. Elastase inhibitor 319, 626, 810, 811, 812, 815, 816, 820, 821, 823, 824. Emetic toxin 502. Endothelin converting enzyme inhibitor 919. Explosive 1032. F F-actin filaments stabilizer, Prodan-actin assay, Inhibits depolymerization of F-actin 670. F-actin inhibitor 579, 584. Factor VIIa inhibitor 142. Factor Xa inhibitor 142. Feeding deterrent, grazers of Lyngbya majuscule 652. Fungicidal 196. G G1 cell cycle arrest and induction of apoptosis 770. G-actin polymerization promoter, Prodan-actin assay 670. Gene cluster for biosynthesis was identified, isolated and analysed 798. Glutamate receptor agonist 863. Growth factor 871. H Hepatotoxic 932. Hepatotoxin 262, 263, 264, 345, 479, 480. High toxic 707. Highly potent suppressor of microtubule dynamics and blocks cells in G2/M phase, 100~1000 times more potent than currently available anticancer drugs such as taxol or vinblastine 505. Highly toxic 1032. Histone deacetylase inhibitor 275, 338, 339, 792. Histone deacetylase inhibitor, MMOA: - selective inhibition of isoforms 1, 2 and 3 276. HIV-1 integrase inhibitor 443. HIV-1 reverse transcriptase inhibitor 693. HIV-rt inhibitor 895. Hypotensive 149. Hypothermic 914.

486

Index 5 Compound Pharmacological Activity Index

I Ichthyotoxin 716, 717. Iionophoric agent 683. IL-1β binding inhibitor, intact EL4.6.1 cells 351. IL-8 receptors inhibitor 1017. IL-12 p40 protein production inhibitor, LPS-stimulated bone marrow-derived dendritic cells 901, 902, 903. Immune system activity, classical complement pathway activator, MMOA: - IgM mediatedeffect 900. Immunomodulating activity 932. Immunosuppressant 767. Immunosuppressive 683, 686, 689. Immunosuppressive, MLR assay 490, 538, 540, 542. Immunosuppressive, MLR assay, lymphocyte viability LCV 741. Immunosuppressive, mus, inhibits mixidlymphocyte response and P388 218. Immunosuppressive, mus, inhibits MLR and P388 217. Indicator organism 645. inducer of apoptosis 848. Induces apoptosis, MCF7 327, 328. Induces arrest in G2/M phase 794. Induces G2/M-cell cycle, cell line not specified 61. Induces production of ROS, strongly 1026, 1027. Induces reporter gene expression, under control of insulin-degrading enzyme promoter 398. Inhibitor of factor VIIa 143, 144, 145, 146. Inhibitor of histone methyltransferase G9A 9, 927, 929, 933, 934. Inhibitor of histone methyltransferase G9A inactive 10, 11. Inhibitor of thrombin 143, 144, 145, 146. Inhibits A549 769. Inhibits amoeboid invasion of hmn tumour cells, having potential to be cell biology tools that can be enlisted to find drug targets for inhibiting amoeboid invasion of tumorcells 257, 258. Inhibits colony formation 918, 931, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968. Inhibits development of starfish 310.

Inhibits development of starfish embryo starfish Asterina pectinifera 306, 307, 308, 309. Inhibits GTP-induced tubulin polymerization 457. inhibits NO and PGE2 production, LPS-induced RAW264.7 718, 719. Inhibits protein expression of molecular chaperone GRP78, HT1080 and MKN74 250. Inhibits settlement of barnacle larvae 7. Inhibits settlement of barnacle larvae Balanus improvises 16, 38. Inhibits SV40 DNA replication 897. Inhibits VEGF secretion 490. Inhibits β5 subunit, chymotrypsin-like activity, Symploca cerevisiae 20S proteasome 151, 152. Inositol 5-phosphatase SHIP1 activator 399. Inotropic 486. Insecticide 267, 484, 579, 977. Ionophore 463, 464. Ionophoric agent 684, 685, 687. Iron chelating activity 153. Isoleucyl transferase inhibitor 993, 994, 995. It might indeed have therapeutic potential against fibrosis 862. K Kinase inhibitor 877, 878, 879, 880, 881, 882, 883, 884, 885, 886. Kinases inhibitor, CaMKIII 953. Kinases inhibitor, CDK4, cyclindependent 246. Kinases inhibitor, PTK 953. L LD50 brine shrimp 418, 419, 794, 917. LD50 goldfish 716. LD50 mus 1032. LD50 mus ipr 10, 118, 162. LD50 mus ivn 899. LD50 mus orl 907, 916, 932, 1030. Lethal brine shrimp 110. Long-acting antagonists of TRPV1 channels, mouse and hmn, pain and in ammation mediators 221. Long-acting hypertensive 907.

Index 5 Compound Pharmacological Activity Index

Luciferase inhibitor, inhibits 2-deoxyglucoseinduced luciferase expression, reporter gene assay, to treat HT1080 cells to increase luciferase activity 248, 249, 250. M MDR inhibitor 427, 426, 428. Metal binding properties, selective 433. Microfilament disruption, microfilament disruption assay, HeLa 579, 584. Microtubule assembly inhibitor 515. Microtubule assembly inhibitor, disruption of microtubule spindle 102, 103. Microtubule inhibitor 197. MLR Inhibitor, hmn two-way MLR 217. Modulator of multidrug resistance, tumour cells 255. Motility inhibition and lytic activities, zoospores of late blight pathogen Phytophthora capsici 844, 845, 846, 847. Motility inhibition and lytic activities, zoospores of Phytophthora capsic 842, 843. MSR inhibitor 456. Muscle contractant 118. Muscle relaxant 907, 914. Mycotoxin 4, 102, 486, 1001. N Na/K-ATPase inhibitor 683, 684, 685, 687. Nematocide 579, 650, 651, 869. Neurophysiological activity, mammals, potent 858. Neuroprotective, hmn dopaminergic neuron assay model of Parkinson’s disease 1011. Neurotoxin 162, 716, 717, 863, 920. NF-κB inhibitor 720. NF-κB inhibitor, blocked TNF-induced NF-κB activation in dose- and time-dependent manner 718, 719. NGF inducer 154, 155. No effect on phosphorylation of AKT, PKD, PLCγ1, or S6 ribosomal protein 181. NO production inhibitor, LPS-stimulated macrophages 386. N-type Ca2+ channel blocker 876.

487

O Odour 937. One of the most prevalent genera in marine environments in class Alphaproteobacteria, Pseudovibrio sp. 698, 699. Osteoporotic agent 46. Oxidoreductase stimulator 865, 866, 867. P PAcF inhibitor 2. PAF-induced platelet aggregation inhibitor 10. Papain inhibitor 319. Peptidic proteasome inhibitor 151, 152. P-Glycoprotein Inhibitor, MDR cancer cells 94. Pharmacologically active nucleoside, caused relaxation of muscles and hypothermia in mice and blocked polysynaptic and monosynaptic reflexes 906. Pheromone, to release eggs 865. Phycotoxin 345, 479, 480. Phytotoxic 31. Phytotoxin associated with fungal diseases of trees 30. PK inhibitor 913. PK inhibitor, selectively inhibits phosphorylation of ERK in NRK cells by PDGF-stimulation 181. PKC inhibitor 918, 975. PLA2 inhibitor 306, 307, 308, 309, 865, 866. PLA2 inhibitor, bee venom PLA2 861. Plant growth regulator 26. Plasmin inhibitor 138, 319, 825. Platelet aggregation inhibitor 904. Potassium channel agonist 920. PP inhibitor 345, 481, 482. PP2A inhibitor 319. Prevents fertilization of sea urchin eggs 689. Protease enzyme cathepsin E inhibitor 229. Proteases elastase inhibitor, strong 804. Protein phosphatase 1 inhibitor 343. PTEN is a identified tumour suppressor gene located on hmn chromosome 10q23.3 972. PTK inhibitor 119. PTP1B inhibitor 487. PTPB inhibitor 474, 475. Pyroglutamyl peptidase inhibitor 120.

488

Index 5 Compound Pharmacological Activity Index

R Rb and K selective ionophore 502. Readily chelates Vanadium 126, 127. Redox-active compound 865. Reduces recruitment barnacle Balanus improvisus and mussel Mytilus edulis, having potential as a non-toxic alternative to heavy-metal-based Antifoulant paints 7, 38. Reinvestigation of same fungal strain revealed presence of additional RHM congeners, RHM3 and RHM4 216. RNA synthesis inhibitor 453, 693. RNA synthetase inhibitor 993, 994, 995. ROS inducer, JurKat, induces strongly production of ROS 1026, 1026. RT inhibitor 894. S Scleritodermin A caused a 5.5-fold increase in induction of apoptosis over the control 457. Sedative 412. Selective metal binding propties 426, 428. Selective serotonin-receptor ligand, targeting 5-HT2A, 5-HT2C and 5-HT4 receptors 7. Selective serotonin-receptor, exclusively targeting 5-HT2C receptor 38. Selectively inhibitory effect, dinoflagellate Prorocentrum micans, no effect on other microalgae and bacteria 286, 287. Serine protease inhibitor 129, 133, 134, 136, 139, 219, 224, 225, 226, 227, 228, 305, 817, 818. Serine protease inhibitor, chymotrypsin 805, 806. Serine protease inhibitor, elastase 805, 806. Serine protease selective inhibitor inactive, chymotripsin 606, 621, 622, 623. Serine protease selective inhibitor inactive, elastase 606. Serine protease selective inhibitor inactive, trypsin 621, 622, 623, 626, 678, 799, 800, 807, 808, 809, 810, 811, 812, 830. Serine protease selective inhibitor, chymotripsin 605, 626, 678, 799, 800, 807, 808, 809, 810, 811, 812, 819, 830. Serine protease selective inhibitor, elastase 605, 621, 622, 623, 626, 694, 695, 696,

799, 799, 800, 800, 810, 811, 812, 813, 819, 830. Serine protease selective inhibitor, trypsin 606, 660. Serine proteases inhibitor 303, 304, 137, 138. Siderophore 120, 153, 177, 178, 179, 180, 372, 373. Siderophore, exceptional affinity for ferric ion 175, 488. Sodium channel VGSC activator, activation of mouse neuroblastoma cells 790, 791. Sortase A inhibitor, Staphylococcus aureus 44. Stimulates antibiotic production 28. Stimulator of actin assembly 789, 779. Stimulator of elastase 652. Stimulatory phytoregulatory activity 100. suggesting promise as a potential treatment for Alzheimer’s disease 398. Surfactant 747, 721, 722, 723, 724, 725, 726, 727. T Thrombin inhibitor 130, 131, 132, 135, 137, 138, 142, 148, 220, 224, 225, 226, 227, 228, 298, 299, 300, 301, 302, 305, 319. Thymidine inhibitor 915. Thymidylate kinase inhibitor 915. Topoisomerase II inhibitor 953, 953. Topoisomerase inhibitor, selective 667, 40. Toxic 267. Toxic, Asterina pectinifera 311, 312. Toxic, brine shrimp 281, 284, 418, 419, 565, 571, 572, 573, 708, 713, 714, 835, 855. Toxic, brine shrimp Artemia salina 13, 19, 45, 73, 76, 77, 78, 347. Toxic, brine shrimp assay 278. Toxic, iv 230. Toxic, mice 793. Toxin 716, 1030. Toxin, crustaceans 826. Transcription factor AP-1 inhibitor 786, 787. Treatment of hyperammonaemia and liver disorders 857. Tremorgenic mycotoxin 118, 42. Trypsin inhibitor 135, 137, 138, 140, 141, 147, 148, 224, 225, 226, 227, 228, 305, 319, 825.

Index 5 Compound Pharmacological Activity Index

Trypsin inhibitor inactive 605, 805, 810, 819. Tubulin polymerisation inhibitor 196, 230. Tumour promoter 345. Tumour promotion activity inhibitor 306. Tyrosinase inhibitor 814. U UV protectant 871.

(The End of HAMNP Volume 8)

UV-A 320~390nm protecting activity 51. α α-Glucosidase inhibitor 873.

489