Tai Lieu Chat Luong Handbook of Anticancer Drugs from Marine Origin Se-Kwon Kim Editor Handbook of Anticancer Drugs from Marine Origin 1 3 Editor Se-Kwon Kim Specialized Graduate School Science & Technology Convergence Department of Marine-Bio Convergence Science Marine Bioprocess Research Center Pukyong National University Yongdong Campus, 365, Sinseon-ro Nam-gu, Busan 608-739 Republic of Korea ISBN 978-3-319-07144-2 ISBN 978-3-319-07145-9 (eBook) DOI 10.1007/978-3-319-07145-9 Springer Cham Heidelberg New York Dordrecht London Library of Congress Control Number: 2014957505 © Springer International Publishing Switzerland 2015 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer Permissions for use may be obtained through RightsLink at the Copyright Clearance Center Violations are liable to prosecution under the respective Copyright Law The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made The publisher makes no warranty, express or implied, with respect to the material contained herein Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Preface—Anticancer Drugs from Marine Origin Over the years, the invention of new compounds are isolated by using advanced technology has expanded significantly There are number of compounds developed from marine environment for the treatment of various diseases Increasing evidence suggested that anticancer drug discovery leads from the marine environment This book combines the knowledge about the compounds isolated from marine environment and their product development This handbook is divided into five parts Chapter 1 provides general introduction and sponges, seaweed, microbes, tunicates and other miscellaneous compounds derived from marine organisms Part I—Sponges (Chaps. 2–6), described the sponge derived drugs represent one of the most promising sources of research for finding new anticancer drugs These chapters discusses about the anticancer and angiogenesis inhibitors isolated from marine sponges and mechanism of action and preclinical and clinical studies Part II—About the marine algae derived compounds on cancer targets (Chaps. 6–11)—explained the compounds isolated from algae species, amelioration and anti tumor effect of a tertiary sulfonium compound, dimethylsulfoniopropionate, carotenoids, polysaccharides etc and the possible mechanisms of action are described Also the health benefits of seaweeds biological roles and potential benefits for female cancers to be discussed in this part Part III—Provides (Chaps. 12–17) the details about marine microbial derived compounds for cancer therapeutics The antitumor compounds isolated from marine microbes such as fungi, bacteria and actinobacteria are discussed Part IV—Discusses (Chap. 18) with marine tunicate derived compounds for cancer therapeutics Part V—The final part of the book covers others marine organisms derived compounds and mechanism of actions In this part sources of the marine compounds, pyridoacridine alkaloids, triterpene glycosides, meroterpenoids for cancer targets such as microtubules, apoptosis, angiogenesis and also discovery and computeraided drug design studies of the anticancer marine triterpene sipholanes as novel P-gp and Brk modulators to be discussed in these chapters This book provides details about compounds isolation, chemistry, and application in detail Hence, anticancer drugs from marine origin are important for academic research, pharmaceutical, nutraceutical and biomedical industries I would v vi Preface—Anticancer Drugs from Marine Origin like to acknowledge Springer publisher, for their encouragement and suggestions to get this wonderful compilation related marine drugs for cancer treatment I would also like to extend my sincere gratitude to all the contributors for providing help, support, and advice to accomplish this task Busan, South Korea Prof Se-Kwon Kim Contents 1 Introduction to Anticancer Drugs from Marine Origin����������������������� 1 Se-Kwon Kim and Senthilkumar Kalimuthu 2 Triterpenoids as Anticancer Drugs from Marine Sponges������������������� 15 Yong-Xin Li and Se-Kwon Kim 3 Marine Sponge Derived Antiangiogenic Compounds��������������������������� 29 Ana R Quesada, Beatriz Martínez-Poveda, Salvador Rodríguez-Nieto and Miguel Ángel Medina 4 Marine Sponge Derived Eribulin in Preclinical and Clinical Studies for Cancer������������������������������������������������������������������������������������ 59 Umang Swami, Umang Shah and Sanjay Goel 5 Antitumour Effect of Cyclodepsipeptides from Marine Sponges�������� 101 Rosa Lemmens-Gruber 6 Cytotoxic Cyclic Peptides from the Marine Sponges���������������������������� 113 Toshiyuki Wakimoto, Karen Co Tan, Hiroki Tajima and Ikuro Abe 7 Fucoidan, A Sulfated Polysaccharides from Brown Algae as Therapeutic Target for Cancer��������������������������������������������������������������� 145 Senthilkumar Kalimuthu and Se-Kwon Kim 8 Seaweeds-Derived Bioactive Materials for the Prevention and Treatment of Female’s Cancer�������������������������������������������������������� 165 Ratih Pangestuti and Se-Kwon Kim 9 Antitumor and Antimetastatic Effects of Marine Algal Polyphenols������������������������������������������������������������������������������������� 177 Fatih Karadeniz and Se-Kwon Kim vii viii Contents 10 Seaweed Carotenoids for Cancer Therapeutics���������������������������������� 185 Meganathan Boominathan and Ayyavu Mahesh 11 Amelioration Effect of a Tertiary Sulfonium Compound, Dimethylsulfoniopropionate, in Green Sea Algae on Ehrlich Ascitic-tumor, Solid Tumor and Related Diseases������������������������������� 205 Kenji Nakajima 12 The Current Status of Novel Anticancer Drugs from Marine Actinobacteria��������������������������������������������������������������������������� 239 Panchanathan Manivasagan and Se-Kwon Kim 13 Natural Products with Anticancer Activity from Marine Fungi������� 253 Valliappan Karuppiah, Fengli Zhang and Zhiyong Li 14 Toluquinol, A Marine Fungus Metabolite, Inhibits Some of the Hallmarks of Cancer����������������������������������������������������������������������� 269 Melissa García-Caballero, Miguel Ángel Medina and Ana R Quesada 15 Anticancer Diketopiperazines from the Marine Fungus�������������������� 301 Zhan-Lin Li and Hui-Ming Hua 16 Meroterpenoids from Marine Microorganisms: Potential Scaffolds for New Chemotherapy Leads���������������������������������������������� 323 Nelson G M Gomes, Suradet Buttachon and Anake Kijjoa 17 Antitumor Compounds from Actinomycetes in Deep-sea Water of Toyama Bay����������������������������������������������������������������������������� 367 Yasuhiro Igarashi 18 Tunicates: A Vertebrate Ancestral Source of Antitumor Compounds��������������������������������������������������������������������������������������������� 383 Edwin L Cooper and Ralph Albert 19 Trabectedin (ET-743) from Marine Tunicate for Cancer Treatment 397 Harika Atmaca and Emir Bozkurt 20 Anti-Cancer Effects of Chitin and Chitosan Derivatives������������������� 413 Mustafa Zafer Karagozlu and Se-Kwon Kim 21 Meroterpenes from Marine Invertebrates: Chemistry and Application in Cancer���������������������������������������������������������������������������� 423 David M Pereira, Patrícia Valentão and Paula B Andrade Contents ix 22 Marine Sponge Sesterpenoids as Potent Apoptosis-Inducing Factors in Human Carcinoma Cell Lines�������������������������������������������� 439 Giuseppina Tommonaro, Salvatore De Rosa, Rosa Carnuccio, Maria Chiara Maiuri and Daniela De Stefano 23 Advances of Microtubule-Targeting Small Molecular Anticancer Agents from Marine Origin����������������������������������������������� 481 Xiaobo Wang, Lun Yu, Zhiguo Liu, Pengfei Xu, Huilong Tan, Tao Wu and Wenbin Zeng 24 Cytotoxic Triterpene Glycosides from Sea Cucumbers���������������������� 515 Valeria P Careaga and Marta S Maier 25 Targeting Cellular Proapoptotic Agents from Marine Sources��������� 529 Ming Liu, Xiukun Lin and Lanhong Zheng 26 Discovery and Computer-Aided Drug Design Studies of the Anticancer Marine Triterpene Sipholanes as Novel P-gp and Brk Modulators������������������������������������������������������������������������������ 547 Ahmed I Foudah, Asmaa A Sallam and Khalid A El Sayed 27 Molecular Targets of Anticancer Agents from Filamentous Marine Cyanobacteria��������������������������������������������������������������������������� 571 Lik Tong Tan and Deepak Kumar Gupta 28 P-gp Inhibitory Activity from Marine Sponges, Tunicates and Algae������������������������������������������������������������������������������������������������ 593 Xiao-cong Huang, Priyank Kumar, Nagaraju Anreddy, Xue Xiao, Dong-Hua Yang and Zhe-Sheng Chen 29 Marine Cyanobacteria Compounds with Anticancer Properties: Implication of Apoptosis���������������������������������������������������� 621 Maria Rosário Martins and Margarida Costa 30 Cytotoxic Cembrane Diterpenoids������������������������������������������������������� 649 Bin Yang, Juan Liu, Junfeng Wang, Shengrong Liao and Yonghong Liu 31 Anti-cancer Effects of Triterpene Glycosides, Frondoside A and Cucumarioside A2-2 Isolated from Sea Cucumbers�������������������� 673 Chang Gun Kim and Jong-Young Kwak 32 Pederin, Psymberin and the Structurally Related Mycalamides: Synthetic Aspects and Biological Activities����������������� 683 Zbigniew J Witczak, Ajay Bommareddy and Adam L VanWert x Contents 33 Antitumor Effects of Sea Hare-Derived Compounds in Cancer�������� 701 Masaki Kita and Hideo Kigoshi 34 Marine Sponge Derived Actinomycetes and Their Anticancer Compounds������������������������������������������������������������������������� 741 Kannan Sivakumar, Panchanathan Manivasagan and Se-Kwon Kim 35 Cytotoxic Terpene-Purines and Terpene-Quinones from the Sea����� 757 Marina Gordaliza 36 Pyridoacridine Alkaloids from Marine Origin: Sources and Anticancer Activity�������������������������������������������������������������������������������� 771 Anake Kijjoa Index���������������������������������������������������������������������������������������������������������������� 803 33 Antitumor Effects of Sea Hare-Derived Compounds in Cancer 725 Fig 33.23 Aplysiatoxin and bryostatin its limited availability from natural sources and its synthetic complexity have hampered studies on its mode of action and development as a therapeutic agent Recently, Irie and co-workers developed a simple and less-lipophilic analogue of tumor-promoting aplysiatoxin, and designated it aplog-1 [194] Aplog-1 was found to be a novel PKC activator with anticancer and anti-tumor-promoting activities Aplog-1 and bryostatin-1 bind selectively to PKC isozymes δ, η, and θ [195], and the unique biological activities of aplog-1 and bryostatin-1 are suggested to be derived from their ability to bind to PKCδ, an isozyme that is involved in apoptosis and which plays a tumor-suppressor role Malyngamides are structurally characterized as N-substituted amides of longchain methoxylated fatty acids with a broad spectrum of bioactivities To date, more than 30 congeners of malyngamides have been identified, and some of them display potential activity as immunosuppressive, anti-inflammatory, anticancer and anti-HIV agents [196, 197] Recently, malyngamide C and its 8-epi-isomer were shown to inhibit bacterial quorum sensing [198, 199] Although malyngamides were primarily isolated from marine cyanobacteria Lyngbya sp., some are derived from sea hares, such as Stylocheilus longicauda (malyngamides O and P) [200], and Bursatella leachii (malyngamides S [201] and X [202]), which are known to accumulate a wide variety of secondary metabolites from their diet (Fig. 33.24) Malyngamide O has a standard C14 fatty acid linked to acyclic amines with an enol methyl ether moiety It exhibits moderate cytotoxicity against P388 mouse lymphoma, A549 human lung carcinoma, and HT29 human colon carcinoma with IC50 values of 2 µg/mL Malyngamide S is a combination of the shorter 12-carbon fatty acid side chain and a highly substituted cyclohexane ring with diketo-functionality It moderately inhibits the proliferation of HL-60 human leukemia cells (IC50 6–8 µM), and exhibits NCI human tumor activity (panel average values: GI50 16.6 µM) Malyngamide X is the first lyngbic acid connected to a new tripeptide backbone, and shows moderate cytotoxicity against KB oral human epidermoid carcinoma and NCI-H187 human small cell lung cancer (ED50 8.2 and 4.1 µM, respectively) Progress in the synthesis of malyngamides was recently reviewed [203] Almost all chemical studies have considered Aplysiidae specimens, whereas there have been few studies of Dolabriferidae mollusks In 1996, Gavagnin and coworkers reported the first chemical study of the tropical opisthobranch Dolabrifera 726 M Kita and H Kigoshi Fig 33.24 Malyngamides dolabrifera (Rang 1828), which led to the isolation of dolabriferol, a propionatederived compound [204] (Note: D dolabrifera is currently classified as the family Aplysiidae.) Its gross and relative stereochemistry was established by X-ray crystallographic analysis The absolute configuration of ( – )-dolabriferol was confirmed by asymmetric total synthesis [205] In addition, the Caribbean mollusk D dolabrifera from Puerto Rico was shown to contain two congeners, dolabriferols B and C [206] Their absolute configurations were determined by chemical degradation and X-ray crystallographic analysis Biological screening of dolabriferols indicated no significant in vitro cytotoxicity toward A2058 melanoma or DU145 prostate cancer cells at 10 µM Dolabriferol C showed weak inhibitory activity against Mycobacterium tuberculosis H37Rv at 128 µg/mL (Fig. 33.25) 33.3.5 Sterol Derivatives Several highly degraded sterols have been reported as constituents of the genus Aplysia Aplykurodin A and B were isolated from the Japanese sea hare A kurodai [207], and related isoprenoids, 4-acetylaplykurodin B and aplykurodinone B, were also identified as ichthyotoxic compounds from the anaspidean mollusk A fasciata collected in the Bay of Naples, Italy (Fig. 33.26) [208] In 1997, a reinvestigation of 33 Antitumor Effects of Sea Hare-Derived Compounds in Cancer 727 Fig 33.25 Dolabriferols Fig 33.26 Marine sterol derivatives the bioactive substances from A fasciata afforded 3-epi-aplykurodinone B, which was shown to be cytotoxic against P388 mouse lymphoma, A549 human lung carcinoma, HT29 human colon carcinoma, and MEL28 human melanoma tumor cell lines in vitro (ED50 values of 2.5 µg/mL in all cases) [209] In 2005, two degraded sterols, aplykurodinones-1 and -2, were isolated from the skin of the sea hare Syphonota geographica collected along the coast of Greece [210] The structure and absolute stereochemistry of aplykurodinone-1 were elucidated through a combination of spectroscopic methods, X-ray crystallography, and chemical correlation Aplykurodinone-1 possesses a cis-fused C–D ring and an unsaturated side-chain The total synthesis of aplykurodinone-1 was accomplished as a racemic form [211], followed by an enantiopure form [212] 33.3.6 Alkaloids Several alkaloids have been isolated from sea hares and their digestive glands Epidithiodioxopiperazine toxins are a class of fungal metabolites Gliocladins A–C are fungal-derived marine alkaloids from a strain of Gliocladium sp., which were originally separated from the sea hare A kurodai (Fig. 33.27) [213] They contain rare dioxo- or trioxopiperazine structures Gliocladins A–C exhibit moderate cytotoxicity against P388 lymphocytic leukemia in cell culture, with gliocladin C being the most potent (IC50 2.4 µg/mL) Their stereostructures were established by NMR spectroscopic analysis, and synthetic studies established their absolute stereostructures [214–216] 728 M Kita and H Kigoshi Fig 33.27 Marine alkaloids Aplaminal, a new triazabicyclo[3.2.1]octane framework metabolite, was isolated from the sea hare A kurodai in 2008 [217] Its structure was determined by the analysis of NMR data and confirmed by an X-ray crystallographic analysis Aplaminal exhibits cytotoxicity against HeLa S3 cells (IC50 0.51 µg/mL) In the same year, ( – )-aplaminal was synthesized in steps in 19 % overall yield and its absolute stereochemistry was confirmed [218] 33.4 Conclusion From sea hares, and especially from the genera Dolabella and Aplysia, a variety of new cytotoxic substances have been isolated, such as dolastatin 10 and aplyronine A, and their chemical and biological properties have been evaluated Synthesis, d erivatization and mode of action studies using chemical probe approaches have contributed to their clinical trials as antitumor agents Meanwhile, due to the scarcity of available natural sources, the biological properties of most of sea hare-derived compounds have rarely been clarified, and there have been particularly few studies on in vivo antitumor effects Further precise and practical chemical syntheses of sea hare-derived compounds and their derivatives, identification of 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