Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Marine-Derived Pharmaceuticals - Challenges and Opportunities

  • Lindequist, Ulrike (Department of Pharmaceutical Biology, Institute of Pharmacy, Ernst-Moritz-Arndt University of Greifswald)
  • Received : 2016.08.11
  • Accepted : 2016.10.05
  • Published : 2016.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

Marine biosphere is the largest one of the earth and harbors an enormous number of different organisms. Living conditions differ fundamentally from those in terrestrial environment. The production of specific secondary metabolites is an important adaption mechanism of marine organisms to survive in the sea. These metabolites possess biological activities which make them interesting as possible drugs for human. The review presents sources, chemistry, production and pharmacology of FDA approved marine derived pharmaceuticals arranged according to their therapeutic indication. Four of the presently seven approved drugs are used for the treatment of cancer. Each another one is applicated for treatment of viral diseases, chronic pain and to lower triglyceride level in blood. Some other products are of interest in diagnostic and as experimental tools. Besides, this article describes challenges in drug development from marine sources, especially the supply problem.

Keywords

References

  1. Aicher, T. D., Buszek, K. R., Fang, F. G., Forsyth, C. J., Jung, S. H., Kishi, Y., Matelich, M. C., Scola, P. M., Spero, D. M. and Yoon, S. K. (1992) Total synthesis of halichondrin B and norhalichondrin B. J. Am. Chem. Soc. 114, 3162-3164. https://doi.org/10.1021/ja00034a086
  2. Anjum, K., Abbas, S. Q., Shah, S. A., Akhter, N., Batool, S. and Hassan, S. S. (2016) Marine sponges as drug treasure. Biomol.Ther. (Seoul) 24, 347-362. https://doi.org/10.4062/biomolther.2016.067
  3. Ansell, S. M. (2011) Brentuximabvedotin: delivering an antimitotic drug to activated lymphoma cells. Expert Opin. Investig. Drugs 20, 99-105. https://doi.org/10.1517/13543784.2011.542147
  4. Bane, V., Lehane, M., Dikshit, M., O'Riordan, A. and Furey, A. (2014) Tetrodotoxin: chemistry, toxicity, source, distribution and detection. Toxins 6, 693-755. https://doi.org/10.3390/toxins6020693
  5. Bergmann, W. and Burke, D. C. (1955) Marine products. XXXIX. The nucleosides of sponges. III. Spongothymidine and spongouridine. J. Org. Chem. 20, 1501-1507. https://doi.org/10.1021/jo01128a007
  6. Bergmann, W. and Feeney, R. J. (1951) Contributions to the study of marine products. XXXII. The nucleosides of sponges. J. Org. Chem. 16, 981-987. https://doi.org/10.1021/jo01146a023
  7. Blunt, J. W., Copp, B. R., Keyzers, R. A., Munro, M. H. and Prinsep, M. R. (2016) Marine natural products. Nat. Prod. Rep. 33, 382-431. https://doi.org/10.1039/C5NP00156K
  8. Bogdanov, A. M., Mishin, A. S., Yampolsky, I. V., Belousov, V. V., Chudakov, D. M., Subach, F. V., Verkhusha, W., Lukyanov, S. and Lukyanov, K. A. (2009) Green fluorescent proteins are light-induced electron donors. Nat. Chem. Biol. 5, 459-461. https://doi.org/10.1038/nchembio.174
  9. Bongiorni, L. and Pietra, F. (1996) Marine natural products for industrial applications. Chem. Ind. 2, 54-58.
  10. Brandon, E. F., Sparidans, R. W., Guijt, K. J., Lowenthal, S., Meijerman, I., Beijnen, J. H. and Schellens, J. H. (2006) In vitro characterization of the human biotransformation and CYP reaction phenotype of ET-743 (Yondelis, Trabectedin), a novel marine anti-cancer drug. Invest. New Drugs 24, 3-14. https://doi.org/10.1007/s10637-005-4538-9
  11. Burgess, J. G. (2012) New and emerging analytical techniques for marine biotechnology. Curr. Opin. Biotechnol. 23, 29-33. https://doi.org/10.1016/j.copbio.2011.12.007
  12. Caron, D. A., Countway, P. D., Jones, A. C., Kim, D. Y. and Schnetzer, A. (2012) Marine protistan diversity. Ann. Rev. Mar. Sci. 4, 467-493. https://doi.org/10.1146/annurev-marine-120709-142802
  13. Carter, N. J. and Keam, S. J. (2010) Trabectedin: a review of its use in soft tissue sarcoma and ovarian cancer. Drugs 70, 355-376.
  14. Census of marine life [Internet] Office of Marine Programs, University of Rhode Island, Graduate School of Oceanography; c2010 [cited 2016 Aug 03]. Available from: http://www.coml.org/.
  15. Cheung, R. C., Ng, T. B., Wong, J. H., Chen, Y. C. and Chan, W. Y. (2016) Marine natural products with anti-inflammatory activity. Appl. Microbiol. Biotechnol. 100, 1645-1666. https://doi.org/10.1007/s00253-015-7244-3
  16. Chini Zitelli, G., Lavista, F., Bastianini, A., Rodolfi, L., Vincenzini, M. and Tredici, M. R. (1999) Production of eicosapentaenoic acid by Nannochloropsis sp. cultures in outdoor tubular photobioreactors. J. Biotechnol. 70, 299-312. https://doi.org/10.1016/S0168-1656(99)00082-6
  17. Cline, J., Braman, J. C. and Hogrefe, H. H. (1996) PCR fidelity of Pfu DNA polymerase and other thermostable DNA polymerases. Nucleic Acids Res. 24, 3546-3551. https://doi.org/10.1093/nar/24.18.3546
  18. Council of Europe (2014) European Pharmacopoeia (Ph. Eur.) (8th edition). Council of Europe.
  19. Cuevas, C. and Francesch, A. (2009) Development of Yondelis (trabectedin, ET-743). A semisynthetic process solves the supply problem. Nat. Prod. Rep. 26, 322-337. https://doi.org/10.1039/b808331m
  20. Debbab, A., Aly, A. H., Lin, W. H. and Proksch, P. (2010) Bioactive compounds from marine bacteria and fungi. Microb. Biotechnol. 3, 544-563. https://doi.org/10.1111/j.1751-7915.2010.00179.x
  21. Deng, C., Pan, B. and O'Connor, O. A. (2013) Brentuximab Vedotin. Clin. Cancer Res. 19, 22-27. https://doi.org/10.1158/1078-0432.CCR-12-0290
  22. Doronina, S. O., Mendelsohn, B. A., Bovee, T. D., Cerveny, C. G., Alley, S. C., Meyer, D. L., Oflazoglu, E., Toki, B. E., Sanderson, R. J., Zabinski, R. F., Wahl, A. F. and Senter, P. D. (2006) Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug. Chem. 17, 114-124. https://doi.org/10.1021/bc0502917
  23. D'Incalci, M., Badri, N., Galmarini, C.M. and Allavena, P. (2014) Trabectedin, a drug acting on both cancer cells and the tumour microenvironment. Br. J. Cancer 111, 646-650. https://doi.org/10.1038/bjc.2014.149
  24. Engene, N., Tronholm, A., Salvador-Reyes, L. A., Luesch, H. and Paul, V. J. (2015) Caldora penicillata gen. nov., comb. nov. (Cyanobacteria), a pantropical marine species with biomedical relevance. J. Phycol. 51, 670-681. https://doi.org/10.1111/jpy.12309
  25. Faulkner, D. J., Harper, M. K., Haygood, M. G., Salomon, C. E. and Schmidt, E. W. (2000) Symbiotic bacteria in sponges: sources of bioactive substances. In Drugs from the Sea (N. Fusetani, Ed.), pp. 107-119. Karger, Basel.
  26. Fenical, W., Jensen, P. R., Palladino, M. A., Lam, K. S., Lloyd, G. K. and Potts, B. C. (2009) Discovery and development of the anticancer agent salinosporamide A (NPI-0052). Bioorg. Med. Chem. 17, 2175-2180. https://doi.org/10.1016/j.bmc.2008.10.075
  27. Fromm, J. R., McEarchem, J. A., Kennedy, D., Thomas, A., Shustov, A. R. and Gopal, A. K. (2012) Clinical binding properties, internalization kinetics, and clinic-pathological activity of brentuximab vedotin: an antibody-drug conjugate for CD30-positive lymphoid neoplasms. Clin. Lymphoma Myeloma Leuk. 12, 280-283. https://doi.org/10.1016/j.clml.2012.01.012
  28. Garnock-Jones, K. P. (2013) Brentuximab vedotin: a review of its use in patients with Hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. Drugs 73, 371-381. https://doi.org/10.1007/s40265-013-0031-5
  29. Giddings, L. A. and Newman, D. J. (2013) Microbial natural products: molecular blue-prints for antitumor drugs. J. Ind. Microbiol. Biotechnol. 40, 1181-1210. https://doi.org/10.1007/s10295-013-1331-1
  30. Gross, H. (2009) Genomic mining - a concept for the discovery of new bioactive natural products. Curr. Opin. Drug Discov. Devel. 12, 207-219.
  31. Grosso, F., D'Incalci, M., Cartaoafa, M., Nieto, A., Fernandez-Teruel, C., Alfaro, V., Lardelli, P., Roy, E., Gomez, J., Kahatt, C., Soto-Matos, A. and Judson, I. (2012) A comprehensive safety analysis confirms rhabdomyolysis as an uncommon adverse reaction in patients treated with trabectedin. Cancer Chemother. Pharmacol. 69, 1557-1565. https://doi.org/10.1007/s00280-012-1864-4
  32. Harris, J. R. and Markl, J. (1999) Keyhole limpet hemocyanin (KLH): a biomedical review. Micron 30, 597-623. https://doi.org/10.1016/S0968-4328(99)00036-0
  33. Hart, J. B., Lill, R. E., Hickford, S. J. H., Blunt, J. W. and Munro, M. H. G. (2000) The halichondrins: chemistry, biology, supply and delivery. In Drugs from the Sea (N. Fusetani, Ed.), pp. 134-153. Karger, Basel.
  34. Hill, R. T. and Fenical, W. (2010) Pharmaceuticals from marine natural products: surge or ebb? Curr. Opin. Biotechnol. 21, 777-779. https://doi.org/10.1016/j.copbio.2010.10.007
  35. Hu, G. P., Yuan, J., Sun, L., She, Z. G., Wu, J. H., Lan, X. J., Zhu, X., Lin, Y. C. and Chen, S. P. (2011) Statistical research on marine natural products based on data obtained between 1985 and 2008. Mar. Drugs 9, 514-525. https://doi.org/10.3390/md9040514
  36. Hu, Y., Chen, J., Hu, G., Yu, J., Zhu, X., Lin, Y., Chen, S. and Yuan, J. (2015) Statistical research on the bioactivity of new marine natural products discovered during the 28 years from 1985 to 2012. Mar. Drugs 13, 202-221. https://doi.org/10.3390/md13010202
  37. Jensen, P. R. and Fenical, W. (2000) Marine microorganisms and drug discovery: current status and future potential. In Drugs from the Sea (N. Fusetani, Ed.), pp. 6-29. Karger, Basel.
  38. Kamat, P. K., Rai, S., Swarnkar, S., Shukla, R. and Nath, C. (2014) Molecular and cellular mechanisms of okadaic acid (OKA)-induced neurotoxicity: a novel tool of Alzheimer's disease therapeutic application. Mol. Neurobiol. 50, 852-865. https://doi.org/10.1007/s12035-014-8699-4
  39. Kiuru, P., D'Auria, M. V., Muller, C. D., Tammela, P., Vuorela, H. and Yli-Kauhaluoma, J. (2014) Exploring marine resources for bioactive compounds. Planta Med. 80, 1234-1246. https://doi.org/10.1055/s-0034-1383001
  40. Klotz, U. (2006) Ziconotide - a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain - a short review. Int. J. Clin. Pharmacol. Ther. 44, 478-483. https://doi.org/10.5414/CPP44478
  41. Koski, R. R. (2008) Omega-3-acid ethyl esters (lovaza) for severe hypertriglyceridemia. P T 33, 271-303.
  42. Konig, G. M. (1992) Meeresorganismen als Quelle pharmazeutisch bedeutsamer Naturstoffe. Dtsch. Apoth. Ztg. 132, 673-683.
  43. Leal, M. C., Madeira, C., Brandao, C. A., Puga, J. and Calado, R. (2012) Bioprospecting of marine invertebrates for new natural products - a chemical and zoogeographical perspective. Molecules 17, 9842-9854. https://doi.org/10.3390/molecules17089842
  44. Li, X. and Qin, L. (2005) Metagenomics-based drug discovery and marine microbial diversity. Trends Biotechnol. 23, 539-543. https://doi.org/10.1016/j.tibtech.2005.08.006
  45. Lindequist, U. and Schweder, T. (2001) Marine Biotechnology. In Biotechnology, Vol. 10: Special processes (H. J. Rehm, Ed.), pp. 441-484. Wiley-VCH, Weinheim.
  46. Luesch, H., Moore, R. E., Paul, V. J., Mooberry, S. L. and Corbett, T. H. (2001) Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1. J. Nat. Prod. 64, 907-910. https://doi.org/10.1021/np010049y
  47. Lopez-Guerrero, J. A., Romero, I. and Poveda, A. (2015) Trabectedin therapy as an emerging treatment strategy for recurrent platinum-sensitive ovarian cancer. Chin. J. Cancer 34, 41-49.
  48. Lowenberg, B. (2013) Sense and nonsense of high-dose cyatarabine for acute myeloid leukemia. Blood 121, 26-28. https://doi.org/10.1182/blood-2012-07-444851
  49. Marmann, A., Aly, A. H., Lin, W., Wang, B. and Proksch, P. (2014) Co-cultivation - a powerful emerging tool for enhancing the chemical diversity of micororganisms. Mar. Drugs 12, 1043-1065. https://doi.org/10.3390/md12021043
  50. Martins, A., Vieira, H., Gaspar, H. and Santos, S. (2014) Marketed marine natural products in the pharmaceutical and cosmeceutical industries: tips for success. Mar. Drugs 12, 1066-1101. https://doi.org/10.3390/md12021066
  51. Maruzzo, M., Brunello, A., Diminutto, A., Rastrelli, M. and Basso, U. (2016) Long-term response to first-line trabectedin in an elderly female patient with a metastatic leiomyosarcoma unfit for anthracycline. Anticancer Drugs 27, 264-267. https://doi.org/10.1097/CAD.0000000000000326
  52. Mayer, A. M., Glaser, K. B., Cuevas, C., Jacobs, R. S., Kem, W., Little, R. D., McIntosh, J. M., Newman, D. J., Potts, B. C. and Shuster, D. E. (2010) The odyssee of marine pharmaceuticals: a current pipeline perspective. Trends Pharmacol. Sci. 31, 255-265. https://doi.org/10.1016/j.tips.2010.02.005
  53. Mayer, A. M. S. (2016) Marine pharmaceuticals: the clinical pipeline. [cited 2016 Aug 01] Available from: http://marinepharmacology.midwestern.edu/clinPipeline.htm/.
  54. Mendola, D. (2000) Aquacultural production of bryostatin 1 and ecteinascidin 743. In Drugs from the Sea (N. Fusetani, Ed.), pp. 120-133. Karger, Basel.
  55. Miljanich, G. P. (2004) Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Curr. Med. Chem. 11, 3029-3040. https://doi.org/10.2174/0929867043363884
  56. Mocz, G. (2007) Fluorescent proteins and their use in marine biosciences, biotechnology, and proteomics. Mar. Biotechnol. 9, 305-328. https://doi.org/10.1007/s10126-006-7145-7
  57. Molinski, T. F., Dalisay, D. S., Lievens, S. L. and Saludes, J. P. (2009) Drug development from marine natural products. Nat. Rev. Drug Discov. 8, 69-85. https://doi.org/10.1038/nrd2487
  58. Morris, P. G. (2010) Advances in therapy: eribulin improves survival for metastatic breast cancer. Anticancer Drugs 21, 885-889. https://doi.org/10.1097/CAD.0b013e32833ed62e
  59. Mullis, K. B. and Falcona, F. A. (1987) Specific synthesis of DNA in vitro via a polymerase-catalyzed chain-reaction. Meth. Enzymol. 155, 335-350. https://doi.org/10.1016/0076-6879(87)55023-6
  60. Mutschler, E., Geisslinger, G., Menzel, S., Ruth, P. and Schmidtko, A. (2016) Pharmakologie kompakt: Allgemeine und Klinische Pharmakologie, Toxikologie. Wissenschaftliche Verlagsgesellschaft Stuttgart. German.
  61. Newman, D. J. and Cragg, G. M. (2004) Marine natural products and related compounds in clinical and advanced preclinical trials. J. Nat. Prod. 67, 1216-1238. https://doi.org/10.1021/np040031y
  62. Newman, D. J. and Cragg, G. M. (2014) Marine-sourced anti-cancer and cancer pain control agents in clinical and late preclinical development. Mar. Drugs 12, 255-278. https://doi.org/10.3390/md12010255
  63. Newman, D. J. and Cragg, G. M. (2016) Drugs and drug candidates from marine sources: an assessment of the current "state of play". Planta Med. 82, 775-789. https://doi.org/10.1055/s-0042-101353
  64. Olivera, B. M., Gray, W. R., Zeikus, R., McIntosh, J. M., Varga, J., Rivier, J., DeSantos, V. and Cruz, L. J. (1985) Peptide neurotoxins from fish-hunting cone snails. Science 230, 1338-1343. https://doi.org/10.1126/science.4071055
  65. Pean, E., Klaar, S., Berglund, E. G., Salmonson, T., Borregaard, J., Hofland, K. F., Ersboll, J., Abadie, E., Giuliani, R. and Pignatti, F. (2012) The European medicines agency review of eribulin for the treatment of patients with locally advanced or metastatic breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. Clin. Cancer Res. 18, 4491-4497. https://doi.org/10.1158/1078-0432.CCR-11-3075
  66. Pro, B., Advani, R., Brice, P., Bartlett, N. L., Rosenblatt, J. D., Illidge, T., Matous, J., Ramchandren, R., Fanale, M., Connors, J. M., Yang, Y., Sievers, E. L., Kennedy, D. A. and Shustov, A. (2012) Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J. Clin. Oncol. 30, 2190-2196. https://doi.org/10.1200/JCO.2011.38.0402
  67. Proksch, P., Putz, A., Ortlepp, S., Kjer, J. and Bayer, M. (2010) Bioactive natural products from marine sponges and fungal endophytes. Phytochem. Rev. 9, 475-489. https://doi.org/10.1007/s11101-010-9178-9
  68. Perez-Victoria, I., Martin, J. and Reyes, F. (2016) Combined LC/UV/MS and NMR strategies for the dereplication of marine natural products. Planta Med. 82, 857-871. https://doi.org/10.1055/s-0042-101763
  69. Radjasa, O. K., Vaske, Y. M., Navarro, G., Vervoort, H. C., Tenney, K., Linington, R. G. and Crews, P. (2011) Highlights of marine invertebrate-derived biosynthetic products: their biomedical potential and possible production by microbial associants. Bioorg. Med. Chem. 19, 6658-6674. https://doi.org/10.1016/j.bmc.2011.07.017
  70. Ramasamy, M. S., Arumugam, P., Manikandan, S. and Murugan, A. (2011) Molecular and combinatorial array of therapeutic targets from conotoxins. Am. J. Drug Discovery Dev. 1, 49-57. https://doi.org/10.3923/ajdd.2011.49.57
  71. Sagar, S., Kaur, M. and Mineman, K. P. (2010) Antiviral lead compounds from marine sponges. Mar. Drugs 8, 2619-2638. https://doi.org/10.3390/md8102619
  72. Schofield, M. M., Jain, S., Porat, D., Dick, G. J. and Sherman, D. H. (2015) Identification and analysis of the bacterial endosymbiont specialized for production of the chemotherapeutic natural product ET-743. Environ. Microbiol. 17, 3964-3975. https://doi.org/10.1111/1462-2920.12908
  73. Schweder, T., Lindequist, U. and Lalk, M. (2005) Screening for new metabolites from marine microorganisms. In Advances in Biochemical Engineering/Biotechnology, Vol. 96: Marine Biotechnology (Y. LeGal and R. Ulber, Eds.), pp. 1-48. Springer, Berlin, Heidelberg.
  74. Shimomura, O. (2009) Discovery of green fluorescent protein (GFP) (Nobel lecture). Angew. Chem. Int. Ed. Engl. 48, 5590-5602. https://doi.org/10.1002/anie.200902240
  75. Skropeta, D. (2008) Deep-sea natural products. Nat. Prod. Rep. 25, 1131-1166. https://doi.org/10.1039/b808743a
  76. Smith, J. A., Wilson, L., Azarenko, O., Zhu, X., Lewis, B. M., Littlefield, B. A. and Jordan, M. A. (2010) Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability. Biochemistry 49, 1331-1337. https://doi.org/10.1021/bi901810u
  77. Snelgrove, P. V. (2016) An ocean of discovery: biodiversity beyond the Census of Marine Life. Planta Med. 82, 790-799. https://doi.org/10.1055/s-0042-103934
  78. Suleria, H. A., Osborne, S., Masci, P. and Gobe, G. (2015) Marinebased nutraceuticals: an innovative trend in the food and supplement industries. Mar. Drugs 13, 6336-6351. https://doi.org/10.3390/md13106336
  79. Sutherland, M. S., Sanderson, R. J., Gordon, K. A., Andreyka, J., Cerveny, C. G., Yu, C., Lewis, T. S., Meyer, D. L., Zabinski, R. F., Doronina, S. O., Senter, P. D., Law, C. L. and Wahl, A. F. (2006) Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J. Biol. Chem. 281, 10540-10547. https://doi.org/10.1074/jbc.M510026200
  80. Takeyama, H., Takeda, D., Yazawa, K., Yamada, A. and Matsunaga, T. (1997) Expression of the eicosapentaenoic acid synthesis gene cluster from Shewanella sp. in a transgenic marine cyanobacterium, Synechococcus sp. Microbiology 143, 2725-2731. https://doi.org/10.1099/00221287-143-8-2725
  81. Tarman, K., Lindequist, U. and Mundt, S. (2013) Metabolites of marine microorganisms and their pharmacological activities. In Marine Microbiology: Bioactive Compounds and Biotechnological Applications (S. K. Kim, Ed.), pp. 393-415. Wiley-VCH, Weinheim.
  82. Terlau, H. and Olivera, B. M. (2004) Conus venoms: a rich source of novel ion channel-targeted peptides. Physiol. Rev. 84, 41-68. https://doi.org/10.1152/physrev.00020.2003
  83. Teuscher, E. and Lindequist, U. (2010) Biogene Gifte. Wissenschaftliche Verlagsgesellschaft, Stuttgart. German.
  84. Thomas, N. V. and Kim, S. K. (2013) Beneficial effects of marine algal compounds in cosmeceuticals. Mar. Drugs 11, 146-164. https://doi.org/10.3390/md11010146
  85. Weinheimer, A. J. and Spraggins, R. L. (1969) The occurrence of two new prostaglandin derivatives (15-epi-PGA2 and its acetate, methyl ester) in the gorgonian Plexaura homomalla chemistry of coelenterates. XV. Tetrahedron Lett. 10, 5185-5188. https://doi.org/10.1016/S0040-4039(01)88918-8
  86. Witte, A. V., Kerti, L., Hermannstadter, H. M., Fiebach, J. B., Schreiber, S. J., Schuchardt, J. P., Hahn, A. and Floel, A. (2014) Long-chain omega-3 fatty acids improve brain function and structure in older adults. Cereb. Cortex 24, 3059-3068. https://doi.org/10.1093/cercor/bht163
  87. World Register of Marine Species [Internet] WoRMS Editorial Board; 2016 [cited 2016 Aug 03]. Available from: http://www.marinespecies.org/.
  88. Wu, C. H. (2009) Palytoxin: membrane mechanisms of action. Toxicon 54, 1183-1189. https://doi.org/10.1016/j.toxicon.2009.02.030
  89. Younes, A., Gopal, A. K., Smith, S. E., Ansell, S. M., Rosenblatt, J. D., Savage, K. J., Ramchandren, R., Bartlett, N. L., Cheson, B. D., de Vos, S., Forero-Torres, A., Moskowitz, C. H., Connors, J. M., Engert, A., Larsen, E. K., Kennedy, D. A., Sievers, E. L. and Chen, R. (2012) Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J. Clin. Oncol. 30, 2183-2189. https://doi.org/10.1200/JCO.2011.38.0410

Cited by

  1. Natural products for human health: an historical overview of the drug discovery approaches 2018, https://doi.org/10.1080/14786419.2017.1356838
  2. Recent Advances in the Isolation, Synthesis and Biological Activity of Marine Guanidine Alkaloids vol.15, pp.10, 2017, https://doi.org/10.3390/md15100324
  3. Marine-Derived Penicillium Species as Producers of Cytotoxic Metabolites vol.15, pp.10, 2017, https://doi.org/10.3390/md15100329
  4. Bioactive Peptides from Marine Ascidians and Future Drug Development–A Review vol.24, pp.1, 2018, https://doi.org/10.1007/s10989-017-9662-9
  5. The Holo-Transcriptome of the Zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa): A Plentiful Source of Enzymes for Potential Application in Green Chemistry, Industrial and Pharmaceutical Biotechnology vol.16, pp.6, 2018, https://doi.org/10.3390/md16060207
  6. Investigation of the Anti-Prostate Cancer Properties of Marine-Derived Compounds vol.16, pp.5, 2018, https://doi.org/10.3390/md16050160
  7. Therapeutic value of steroidal alkaloids in cancer: Current trends and future perspectives pp.00207136, 2019, https://doi.org/10.1002/ijc.31965
  8. Two Isospongian Diterpenes from the Sponge Luffariella sp vol.12, pp.7, 2016, https://doi.org/10.1177/1934578x1701200702
  9. Marine sponge microbial association: Towards disclosing unique symbiotic interactions vol.140, pp.None, 2018, https://doi.org/10.1016/j.marenvres.2018.04.017
  10. The complete genome sequence of a marine sponge-associated bacteria, Bacillus safensis KCTC 12796BP, which produces the anti-allergic compounds vol.54, pp.4, 2018, https://doi.org/10.7845/kjm.2018.8069
  11. Structures, Activities and Drug-Likeness of Anti-Infective Xanthone Derivatives Isolated from the Marine Environment: A Review vol.24, pp.2, 2019, https://doi.org/10.3390/molecules24020243
  12. Diversity, Ecology, and Prevalence of Antimicrobials in Nature vol.10, pp.None, 2016, https://doi.org/10.3389/fmicb.2019.02518
  13. Marine natural products as source of new drugs: a patent review (2015-2018) vol.29, pp.4, 2016, https://doi.org/10.1080/13543776.2019.1598972
  14. Marine-Derived Natural Lead Compound Disulfide-Linked Dimer Psammaplin A: Biological Activity and Structural Modification vol.17, pp.7, 2016, https://doi.org/10.3390/md17070384
  15. Coral and Coral-Associated Microorganisms: A Prolific Source of Potential Bioactive Natural Products vol.17, pp.8, 2016, https://doi.org/10.3390/md17080468
  16. Design and Synthesis of Anti-Cancer Chimera Molecules Based on Marine Natural Products vol.17, pp.9, 2016, https://doi.org/10.3390/md17090500
  17. Structural characterization of novel comb-like branched α-D-glucan from Arca inflata and its immunoregulatory activities in vitro and in vivo vol.10, pp.10, 2016, https://doi.org/10.1039/c9fo01395d
  18. Bright Spots in The Darkness of Cancer: A Review of Starfishes-Derived Compounds and Their Anti-Tumor Action vol.17, pp.11, 2016, https://doi.org/10.3390/md17110617
  19. A Review on Molecular Mechanisms and Patents of Marine-derived Anti-thrombotic Agents vol.21, pp.None, 2016, https://doi.org/10.2174/1389450121666201020151927
  20. Marine Bioresource Development - Stakeholder’s Challenges, Implementable Actions, and Business Models vol.7, pp.None, 2016, https://doi.org/10.3389/fmars.2020.00062
  21. A New Network for the Advancement of Marine Biotechnology in Europe and Beyond vol.7, pp.None, 2016, https://doi.org/10.3389/fmars.2020.00278
  22. Advancing Through the Pandemic From the Perspective of Marine Graduate Researchers: Challenges, Solutions, and Opportunities vol.7, pp.None, 2016, https://doi.org/10.3389/fmars.2020.00528
  23. Metagenomics Approaches in Discovery and Development of New Bioactive Compounds from Marine Actinomycetes vol.77, pp.4, 2016, https://doi.org/10.1007/s00284-019-01698-5
  24. Screening Marine Natural Products for New Drug Leads against Trypanosomatids and Malaria vol.18, pp.4, 2016, https://doi.org/10.3390/md18040187
  25. Inhibition of Microbial Quorum Sensing Mediated Virulence Factors by Pestalotiopsis sydowiana vol.30, pp.4, 2016, https://doi.org/10.4014/jmb.1907.07030
  26. Collective Locomotion of Human Cells, Wound Healing and Their Control by Extracts and Isolated Compounds from Marine Invertebrates vol.25, pp.11, 2016, https://doi.org/10.3390/molecules25112471
  27. Highlights of marine natural products having parallel scaffolds found from marine-derived bacteria, sponges, and tunicates vol.73, pp.8, 2016, https://doi.org/10.1038/s41429-020-0330-5
  28. Exploring Antimicrobials from the Flora and Fauna of Marine: Opportunities and Limitations vol.17, pp.4, 2016, https://doi.org/10.2174/1570163816666190819141344
  29. Cardiovascular Active Peptides of Marine Origin with ACE Inhibitory Activities: Potential Role as Anti-Hypertensive Drugs and in Prevention of SARS-CoV-2 Infection vol.21, pp.21, 2016, https://doi.org/10.3390/ijms21218364
  30. Microbial Activity in Subterranean Ecosystems: Recent Advances vol.10, pp.22, 2016, https://doi.org/10.3390/app10228130
  31. Nanoliposomal Cercodemasoide A and Its Improved Activities Against NTERA-2 Cancer Stem Cells vol.15, pp.12, 2016, https://doi.org/10.1177/1934578x20982108
  32. Utilization of Shrimp waste as a novel media for marine bacteria isolation vol.11, pp.1, 2016, https://doi.org/10.1007/s13205-020-02564-z
  33. Marine-Derived Secondary Metabolites as Promising Epigenetic Bio-Compounds for Anticancer Therapy vol.19, pp.1, 2016, https://doi.org/10.3390/md19010015
  34. Drug Development from Peptide-derived Marine Natural Products vol.1011, pp.None, 2021, https://doi.org/10.1088/1757-899x/1011/1/012063
  35. Bioactivity and Biotechnological Overview of Naturally Occurring Compounds from the Dinoflagellate Family Symbiodiniaceae: A Systematic Review vol.2021, pp.None, 2021, https://doi.org/10.1155/2021/1983589
  36. An overview of potential inhibitors targeting non-structural proteins 3 (PLpro and Mac1) and 5 (3CLpro/Mpro) of SARS-CoV-2 vol.19, pp.None, 2016, https://doi.org/10.1016/j.csbj.2021.08.036
  37. Marine-derived drugs: Recent advances in cancer therapy and immune signaling vol.134, pp.None, 2016, https://doi.org/10.1016/j.biopha.2020.111091
  38. Bioactivity Screening and Gene-Trait Matching across Marine Sponge-Associated Bacteria vol.19, pp.2, 2016, https://doi.org/10.3390/md19020075
  39. 1,2,4‐Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells, Targeting GSK3β Kinase vol.16, pp.3, 2021, https://doi.org/10.1002/cmdc.202000752
  40. Field-Template, QSAR, Ensemble Molecular Docking, and 3D-RISM Solvation Studies Expose Potential of FDA-Approved Marine Drugs as SARS-CoVID-2 Main Protease Inhibitors vol.26, pp.4, 2016, https://doi.org/10.3390/molecules26040936
  41. Secondary Metabolites from the Marine Sponges of the Genus Petrosia: A Literature Review of 43 Years of Research vol.19, pp.3, 2016, https://doi.org/10.3390/md19030122
  42. Marine sponge-derived/inspired drugs and their applications in drug delivery systems vol.13, pp.5, 2016, https://doi.org/10.4155/fmc-2020-0123
  43. Quercetin and Its Nano-Scale Delivery Systems in Prostate Cancer Therapy: Paving the Way for Cancer Elimination and Reversing Chemoresistance vol.13, pp.7, 2021, https://doi.org/10.3390/cancers13071602
  44. Antiplasmodial Compounds from Deep-Water Marine Invertebrates vol.19, pp.4, 2016, https://doi.org/10.3390/md19040179
  45. Anti-Alzheimer’s Molecules Derived from Marine Life: Understanding Molecular Mechanisms and Therapeutic Potential vol.19, pp.5, 2016, https://doi.org/10.3390/md19050251
  46. Promising Activities of Marine Natural Products against Hematopoietic Malignancies vol.9, pp.6, 2021, https://doi.org/10.3390/biomedicines9060645
  47. Genome sequence of Aspergillus flavus A7, a marine-derived fungus with antibacterial activity vol.64, pp.7, 2016, https://doi.org/10.1139/gen-2020-0066
  48. Exploitation of Marine Molecules to Manage Alzheimer’s Disease vol.19, pp.7, 2016, https://doi.org/10.3390/md19070373
  49. Marine Natural Products as Anticancer Agents vol.19, pp.8, 2016, https://doi.org/10.3390/md19080447
  50. Potential role of marine species-derived bioactive agents in the management of SARS-CoV-2 infection vol.16, pp.16, 2016, https://doi.org/10.2217/fmb-2021-0024
  51. Cytotoxic Indole-Diterpenoids from the Marine-Derived Fungus Penicillium sp. KFD28 vol.19, pp.11, 2021, https://doi.org/10.3390/md19110613
  52. Untapped Potential of Marine-Associated Cladosporium Species: An Overview on Secondary Metabolites, Biotechnological Relevance, and Biological Activities vol.19, pp.11, 2016, https://doi.org/10.3390/md19110645
  53. Three Novel Bacteria Associated with Two Centric Diatom Species from the Mediterranean Sea, Thalassiosira rotula and Skeletonema marinoi vol.22, pp.24, 2016, https://doi.org/10.3390/ijms222413199
  54. From Life in the Sea to the Clinic: The Marine Drugs Approved and under Clinical Trial vol.11, pp.12, 2016, https://doi.org/10.3390/life11121390
  55. 갯벌 방선균 유래 Boholamide A의 구조 및 생리활성에 대한 연구 vol.52, pp.4, 2016, https://doi.org/10.22889/kjp.2021.52.4.203
  56. Antiviral Strategies Using Natural Source-Derived Sulfated Polysaccharides in the Light of the COVID-19 Pandemic and Major Human Pathogenic Viruses vol.14, pp.1, 2016, https://doi.org/10.3390/v14010035
  57. Resonance Raman and SERRS of fucoxanthin: Prospects for carotenoid quantification in live diatom cells vol.1250, pp.p1, 2016, https://doi.org/10.1016/j.molstruc.2021.131608