Vestnik of the Far East Branch of the Russian Academy of SciencesVestnik of the Far East Branch of the Russian Academy of SciencesВестник Дальневосточного отделения Российской академии наук0869-7698The Russian Academy of Sciences67603210.31857/S0869769824030011ISWKGZChemical Sciences. For the 60th anniversary of the G.B. Elyakov Pacific Institute of Bioorganic Chemistry FEB RASХимические науки. К 60-летию Тихоокеанского института биоорганической химии им. Г.Б. Елякова ДВО РАНReview ArticleMarine natural products: the long road to drug discoveryМорские природные продукты: долгий путь к открытию лекарствKimHyoung KyuКимХен Кю
Korea, Democratic People's Republic of

доктор философии, профессор, профессор, профессор

PhD, Professor, Professor, Professor

estrus74@gmail.comGarciaMaria Victoria Faith V.ГарсияМария Виктория Фейт В.
Korea, Democratic People's Republic of

PhD, Post-doctoral Researcher, Post-doctoral Researcher

доктор философии, докторант-исследователь, докторант, научный сотрудник

victoriafaith.garcia@gmail.comShepetovaNatalia M.ШепетоваНаталья Михайловна
Korea, Democratic People's Republic of

Assistant Director for International Relations

помощник директора по международным связям

piboc@bk.ruHanJinХанДжин
Korea, Democratic People's Republic of

MD, PhD, Professor, Director, Professor, Professor

доктор медицины, доктор философии, профессор, директор, профессор, профессор

phyhanj@inje.ac.krCardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, College of Medicine, Inje UniversityЦентр сердечно-сосудистых и метаболических заболеваний, Центр морской терапии, Медицинский колледж, Университет ИнджеDepartment of Health Sciences and Technology, Graduate School of Inje UniversityФакультет медицинских наук и технологий, Высшая школа Университета ИнджеDepartment of Physiology, College of Medicine, Inje UniversityКафедра физиологии, Медицинский колледж, Университет ИнджеG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far East Branch of the Russian Academy of SciencesТихоокеанский институт биоорганической химии имени Г.Б. Елякова ДВО РАН150620243123628022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-7698/article/view/676032

The collaboration between various research institutions in South Korea and G.B. Elyakov Pacific Institute of Bioorganic Chemistry (PIBOC) in Russia started 30 years ago in 1993. Since then, we have been actively conducting marine biotechnology and pharmaceutical research. For nearly 20 years, this successful partnership has been led by the exceptional “conductor” Valentin Stonik, who has formed an exquisite harmony “orchestra” that we have named KORUS MUSIC (Korea-Russia collaboration for Marine Unlimitedre Sources for Innovation and Creation). The purpose of this review paper is to present the history of KORUS MUSIC and highlight the significant advances achieved through our joint research, and to outline plans for our future collaboration and joint efforts for the next 20 years. This article is a synthesis of science and poetry, of the history of friendly relations and dreams of a common future. It is dedicated to the 80th anniversary of Prof. Stonik, to the 60th anniversary of PIBOC and to the 30th anniversary of collaboration between the Korean and Russian scientists.

Сотрудничество между научно-исследовательскими институтами Южной Кореи и Тихоокеанским институтом биоорганической химии имени Г.Б. Елякова (ТИБОХ) в России началось 30 лет назад, в 1993 году. С тех пор мы активно ведем исследования в области морской биотехнологии и фармацевтики. На протяжении почти 20 лет это успешное партнерство возглавлял выдающийся “дирижер” профессор Валентин Стоник, сформировавший изысканный гармоничный “оркестр”, который мы назвали KORUS MUSIC (Korea-Russia collaboration for Marine Unlimitedre Sources for Innovation and Creation). Цель данной обзорной статьи – рассказать об истории создания KORUS MUSIC и отметить значительные успехи, достигнутые в ходе наших совместных исследований, а также наметить планы нашего дальнейшего сотрудничества и совместных усилий на ближайшие 20 лет.

marine natural productsfrondosidecucumariosidestichoposideechinochromespinochromeneopetrosideморские природные продуктыфрондозидкукумариозидстихопозидэхинохромспинохромнеопетрозидНациональный исследовательского фонда КореиNational Research Foundation of KoreaRS-2023-00270463Национальный исследовательского фонда КореиNational Research Foundation of KoreaRS-2023-00221673Корейский институт фундаментальных наукKorean Institute of Fundamental Sciences2023RIA6C101B008This work was supported by the Basic Research Laboratory program and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korean government (RS-2023-00270463 and RS-2023-00221673) and by Korea Basic Science Institute (National Research Facilities and Equipment Center) grant funded by the Ministry of Education (2023RIA6C101B008).Эта работа была поддержана программой Лаборатории фундаментальных исследований и программой фундаментальных научных исследований Национального исследовательского фонда Кореи (NRF), финансируемой правительством Кореи (RS-2023-00270463 и RS-2023-00221673), а также грантом Корейского института фундаментальных наук (Национальный центр научно-исследовательских учреждений и оборудования), финансируемым Национальным исследовательским фондом Кореи (National Research Facilities and Equipment Center). Министерство образования (2023RIA6C101B008).Banerjee P., Mandhare A., Bagalkote V. Marine natural products as source of new drugs: an updated patent review (July 2018–July 2021) // Expert Opinion on Therapeutic Patents. 2022. Vol. 32, N. 3. P. 317–363.Sigwart J. D., Blasiak R., Jaspars M., Jouffray J.-B., Tasdemir D., Unlocking the potential of marine biodiscovery // Nat. Prod. Reports. 2021. Vol. 38, N. 7. P. 1235–1242.Rotter A., Bacu A., Barbier M., Bertoni F., Bones A. M., Cancela, M.L., Carlsson J., Carvalho, M.F., Cegłowska M., Dalay M. C. A new network for the advancement of marine biotechnology in Europe and beyond // Front. Mar. Sci. 2020. Vol. 7. Art. 278. https://doi.org/10.3389/fmars.2020.00278.Haque N., Parveen S., Tang T., Wei J., Huang Z. Marine natural products in clinical use // Mar. Drugs. 2022. Vol. 20, N. 8. Art. 528 [1–40].Donia M., Hamann M. T. Marine natural products and their potential applications as anti-infective agents // Lancet Infect. Diseas. 2003. Vol. 3, N. 6. P. 338–348.Jeong S. H., Kim H. K., Song I. S., Lee S. J., Ko K. S., Rhee B. D., Kim N., Mishchenko N. P., Fedoryev S. A., Stonik, V.A., Han J. Echinochrome A protects mitochondrial function in cardiomyocytes against cardiotoxic drugs // Mar. Drugs. 2014. Vol. 12, N. 5. P. 2922–2936.Jeong S. H., Kim H. K., Song I. S., Noh S. J., Marquez J., Ko K. S., Rhee B. D., Kim N., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Han J. Echinochrome a increases mitochondrial mass and function by modulating mitochondrial biogenesis regulatory genes // Mar. Drugs. 2014. Vol. 12, N. 8. P. 4602–4615.Lee S. R., Pronto J. R., Sarankhuu B. E., Ko K. S., Rhee B. D., Kim N., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Han J. Acetylcholinesterase inhibitory activity of pigment echinochrome A from sea urchin Scaphechinus mirabilis // Mar. Drugs. 2014. Vol. 12, N. 6. P. 3560–3573.Kim H. K., Youm J. B., Jeong S. H., Lee S. R., Song I. S., Ko T. H., Pronto J. R., Ko K. S., Rhee B. D., Kim N., Nilius B., Mischchenko N. P., Fedoreyev S. A., Stonik V. A., Han J. Echinochrome A regulates phosphorylation of phospholamban Ser16 and Thr17 suppressing cardiac SERCA2A Ca²⁺ reuptake // Pflugers Arch. 2015. Vol. 467, N. 10. P. 2151–2163.Shubina L. K., Makarieva T. N., Yashunsky D. V., Nifantiev N. E., Denisenko V. A., Dmitrenok, P.S., Dyshlovoy S. A., Fedorov S. N., Krasokhin V. B., Jeong S. H., Han J., Stonik V. A. Pyridine nucleosides neopetrosides A and B from a marine Neopetrosia sp. sponge. Synthesis of neopetroside A and its β-riboside fnalogue // J. Nat. Prod. 2015. Vol. 78, N. 6. P. 1383–1389.Seo D. Y., McGregor R.A., Noh S. J., Choi S. J., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Han J. Echinochrome A improves exercise capacity during short-term endurance training in rats // Mar. Drugs. 2015. Vol. 13, N. 9. P. 5722–5731.Yoon C. S., Kim H. K., Mishchenko N. P., Vasileva E. A., Fedoreyev, S.A., Stonik V. A., Han J. Spinochrome D attenuates doxorubicin-induced cardiomyocyte death via improving glutathione metabolism and attenuating oxidative stress // Mar. Drugs. 2018. Vol. 17, N. 1. Art. 2 [1–20].Kim H. K., Cho S. W., Heo H. J., Jeong S. H., Kim M., Ko K. S., Rhee B. D., Mishchenko N. P., Vasileva E. A., Fedoreyev S. A., Stonik V. A., Han J. A novel atypical PKC-Iota inhibitor, echinochrome A, enhances cardiomyocyte differentiation from mouse embryonic stem cells // Mar. Drugs. 2018. Vol. 16, No. 6. Art. 192 [1–14].Yoon C. S., Kim H. K., Mishchenko N. P., Vasileva E. A., Fedoreyev S. A., Shestak O. P., Balaneva N. N., Novikov V. L., Stonik V. A., Han J. The protective effects of echinochrome A structural analogs against oxiative stress and doxorubicin in AC16 cardiomyocytes // Mol. Cell. Toxicol. 2019. Vol. 15. P. 407–414.Park J. H., Lee N. K., Lim H. J., Mazumder S., Rethineswaran K. V., Kim Y. J., Jang, W. B.; Ji S. T., Kang S., Kim D. Y., Van L. T.H., Giang L. T.T., Kim D. H., Ha J. S., Yun J., Kim H., Han J., Mishchenko N. P., Fedoreyev S. A., Vasileva E. A., Kwon S. M., Baek S. H. Therapeutic cell protective role of histochrome under oxidative stress in human cardiac progenitor cells // Mar. Drugs. 2019. Vol. 17, N. 6. Art. 368 [1–15].Kim R., Hur D., Kim H. K., Han J., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Chang W. Echinochrome A attenuates cerebral ischemic injury through regulation of cell survival after middle cerebral artery occlusion in rat // Mar. Drugs. 2019. Vol. 17, N. 9. Art. 501 [1–8].Oh S. J., Seo Y., Ahn J. S., Shin Y. Y., Yang J. W., Kim H. K., Han J., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Kim H. S. Echinochrome A reduces colitis in mice and induces in vitro generation of regulatory immune cells // Mar. Drugs. 2019. Vol. 17. N. 11. Art. 622 [1–10].Park G. B., Kim M. J., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Han J., Lee H. S., Kim D., Jeong J. Y. Echinochrome A promotes ex vivo expansion of peripheral blood-derived CD34(+) cells, potentially through downregulation of ROS production and activation of the Src-Lyn-p110δ pathway // Mar. Drugs. 2019. Vol. 17, N. 9. Art. 526 [1–14].Kim J. M., Kim J. H., Shin S. C., Park G. C., Kim H. S., Kim K., Kim H. K., Han J., Mishchenko N. P., Vasileva E. A., Fedoreyev S. A., Stonik V. A., Lee B. J. The protective effect of echinochrome A on extracellular matrix of vocal folds in ovariectomized rats // Mar. Drugs. 2020. Vol. 18, N. 2. Art. 77 [1–15].Yun H. R., Ahn S. W., Seol B., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Han J., Ko K. S., Rhee B. D., Seol J. E., Kim H. K. Echinochrome A treatment alleviates atopic dermatitis-like skin lesions in NC/Nga mice via IL-4 and IL-13 suppression // Mar. Drugs. 2021. V. 19, N. 11 Art. 622 [1–11].Seol J. E., Ahn S. W., Seol B., Yun H. R., Park N., Kim H. K., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Han J. Echinochrome A protects against ultraviolet B-induced photoaging by lowering collagen degradation and inflammatory cell infiltration in hairless mice // Mar. Drugs. 2021. Vol. 19, N. 10. Art. 550 [1–13].Park G. T., Yoon J. W., Yoo S. B., Song Y. C., Song P., Kim H. K., Han J., Bae S. J., Ha K. T., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Kim M. B., Kim J. H. Echinochrome A treatment alleviates fibrosis and inflammation in bleomycin-induced scleroderma // Mar. Drugs. 2021. Vol. 19, N. 5. Art. 237 [1–11].Kim H. K., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Han J., Multifaceted clinical effects of echinochrome // Mar. Drugs. 2021. Vol. 19, N. 8. Art. 412 [1–16].Song B. W., Kim S., Kim R., Jeong S., Moon H., Kim H., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Lee M. Y., Kim J., Kim H. K., Han J., Chang W. Regulation of inflammation-mediated endothelial to mesenchymal transition with echinochrome A for improving myocardial dysfunction // Mar. Drugs. 2022. Vol. 20, N. 12. Art. 756 [1–17].Choi M. R., Lee H., Kim H. K., Han J., Seol J. E., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Ju W. S., Kim D. J., Lee S. R., Echinochrome A inhibits melanogenesis in B16F10 cells by downregulating CREB signaling // Mar. Drugs. 2022. Vol. 20, N. 9. Art. 555 [1–12].Ahn J. S., Shin Y. Y., Oh S. J., Song M. H., Kang M. J., Park S. Y., Nguyen P. T., Nguyen, D. K., Kim H. K., Han J., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Seo Y., Lee B. C., Kim H. S. Implication of echinochrome A in the plasticity and damage of intestinal epithelium // Mar Drugs. 2022, No. 20, N. 11. Art. 715 [1–14].Kim J. M., Shin S. C., Cheon Y. I., Kim H. S., Park G. C., Kim H. K., Han J., Seol J. E., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Lee B. J., Effect of echinochrome A on submandibular gland dysfunction in ovariectomized rats // Mar. Drugs. 2022. Vol. 20, N. 12. Art. 729 [1–14].Tang X., Nishimura A., Ariyoshi K., Nishiyama K., Kato Y., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Kim H. K., Han J., Kanda Y., Umezawa K., Urano Y., Akaike T., Nishida M. Echinochrome prevents sulfide catabolism-associated chronic heart failure after myocardial infarction in mice // Mar. Drugs. 2023. Vol. 21, N. 1. Art. 52 [1–17].Han D. G., Kwak J., Choi E., Seo S. W., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Kim H. K., Han J., Byun J. H., Jung I. H., Yun H., Yoon I. S. Physicochemical characterization and phase II metabolic profiling of echinochrome A, a bioactive constituent from sea urchin, and its physiologically based pharmacokinetic modeling in rats and humans // Biomed. Pharmacother. 2023. Vol. 162. Art. 114589 [1–16].Kim S. E., Chung E. D.S., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Kim H. K., Nam J. H., Kim S. J. Multiple effects of echinochrome A on selected ion channels implicated in skin physiology // Mar. Drugs. 2023. Vol. 21, No. 2. Art. 78 [1–16]Pham T. K., Nguyen T. H.T., Yun H. R., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Vu T. T., Nguyen H. Q., Cho S. W., Kim H. K., Han J. Echinochrome A prevents diabetic nephropathy by inhibiting the PKC-iota pathway and enhancing renal mitochondrial function in db/db mice // Mar. Drugs. 2023. Vol. 21, N. 4. Art. 222 [1–15].Jin J. O., Shastina V. V., Shin S. W., Xu Q., Park J. I., Rasskazov V. A., Avilov S. A., Fedorov, S.N., Stonik V. A., Kwak J. Y., Differential effects of triterpene glycosides, frondoside A and cucumarioside A2-2 isolated from sea cucumbers on caspase activation and apoptosis of human leukemia cells // FEBS Lett. 2009. Vol. 583, N. 4. P. 697–702.Park J. I., Bae H. R., Kim C. G., Stonik V. A., Kwak J. Y., Relationships between chemical structures and functions of triterpene glycosides isolated from sea cucumbers // Front. Chem. 2014. Vol. 2. Art. 77 [1–14].Yun S. H., Park E. S., Shin, S.W., Na Y. W., Han J. Y., Jeong J. S., Shastina V. V., Stonik V. A., Park J. I., Kwak J. Y. Stichoposide C induces apoptosis through the generation of ceramide in leukemia and colorectal cancer cells and shows in vivo antitumor activity // Clin. Cancer Res. 2012. Vol. 18, N. 21. P. 5934–5948.Yun S. H., Park E. S., Shin S. W., Ju M. H.; Han, J.Y., Jeong J. S., Kim S. H., Stonik V. A., Kwak J. Y., Park J. I. By activating Fas/ceramide synthase 6/p38 kinase in lipid rafts, stichoposide D inhibits growth of leukemia xenografts // Oncotarget. 2015. Vol. 6, N. 29. P. 27596–27612.Yun S. H., Sim E. H., Han S. H., Kim T. R., Ju M. H., Han J. Y., Jeong J. S., Kim S. H., Silchenko A. S., Stonik V. A., Park J. I. In vitro and in vivo anti-leukemic effects of cladoloside C2 are mediated by activation of Fas/ceramide synthase 6/p38 kinase/c-Jun NH2-terminal kinase/caspase-8 // Oncotarget. 2018 Vol. 9, N. 1. P. 495–511.Cui H., Liu J., Vasileva E. A., Mishchenko N. P., Fedoreyev S. A., Stonik V. A., Zhang, Y., Echinochrome A reverses kidney abnormality and reduces blood pressure in a rat model of preeclampsia // Mar. Drugs. 2022. Vol. 20, N. 11. Art. 722 [1–13].Daniotti S., Re I. Marine biotechnology: challenges and development market trends for the enhancement of biotic resources in industrial pharmaceutical and food applications. A statistical analysis of scientific literature and business models // Mar. Drugs. 2021. Vol. 19. N. 2. Art. 61 [1–35].Lindequist U. Marine-derived pharmaceuticals–challenges and opportunities // Biomol. Ther. 2016. Vol. 24, N. 6. 561–571.OECD, Marine Biotechnology and the Bioeconomy. Paris: OECD, 2012.