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Drug Leads Derived from Japanese Marine Organisms

[ Vol. 28 , Issue. 1 ]

Author(s):

Daisuke Uemura*, Yoshinori Kawazoe*, Toshiyasu Inuzuka, Yuki Itakura, Chiari Kawamata and Takahiro Abe*   Pages 196 - 210 ( 15 )

Abstract:


Many natural products with extraordinary chemical structures and brilliant biological activities have been obtained from marine organisms. We have investigated such fascinating bioactive molecules, exemplified by the potent marine toxin palytoxin and the antitumor molecule halichondrin B, which has been developed as the anticancer drug HalavenĀ®, to explore novel frontiers in organic chemistry and bioscience 1. Working within the traditional discipline, we have sought to acquire a deeper understanding of biological phenomena. We introduce here our major work along with up-todate topics. We isolated yoshinone A from marine cyanobacteria and completed a gram-scale synthesis. Yoshinone A is a novel polyketide that inhibited the differentiation of 3T3-L1 cells into adipocytes without significant cytotoxicity. The detailed mechanisms of action will be elucidated via further experiments in vitro and in vivo. In this study, we explore the true producers of okadaic acid and halichondrin B by immunostaining of Halichondria okadai with an antibody that was prepared using these natural products as an antigen. We will analyze isolated symbionts and reveal biosynthetic pathways.

Keywords:

Natural products, halichondrin B, yoshinone A, terpenoids, symbiotic bacteria, metagenomic analysis, halichrome A, okadaic acid.

Affiliation:

Institute for Advanced Research (Emeritus), Nagoya University, Nagoya, Center for Education and Research in Agricultural Innovation, Faculty of Agriculture, Saga University, Karatsu, Life Science Research Center, Gifu University, Gifu, Department of Chemistry, Faculty of Science, Kanagawa University, Hiratsuka, Department of Chemistry, Faculty of Science, Kanagawa University, Hiratsuka, Department of Chemistry, Faculty of Science, Kanagawa University, Hiratsuka



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