题  目：Bioorganic-chemical study on antitumor/cytotoxic macrolides

报告人：Prof. Hideo Kigoshi

University of Tsukuba

上海中医药大学

主持人：洪  然 研究员

时  间：2026年1月20日(星期二) 15:30

地  点：君谋楼二楼  第一会议室

欢迎听讲！

【Abstract】

Actin is a major cytoskeletal protein in eukaryotes. Among actin-binding natural products, aplyronine A (ApA) and scytophycin B (ScB) exhibit potent cytotoxicity.

We isolated, structurally determined, and synthesized ApA, an antitumor marine macrolide. After SAR and chemical-biological studies, we found the unique mode of action: 1) ApA binds to actin to depolymerize fibrous actin to globular actin, 2) ApA-actin complex binds to tubulin, another cytoskeletal protein, to form the ternary complex pf ApA-actin-tubulin, 3) the ternary complex inhibits tubulin polymerization, resulting in formation of abnormal spindle, 4) this disruption of mitosis induces apoptosis.

Scytophycins are cytotoxic macrolides, and the cytotoxicity was reported to vary with the structures of the macrolactone moiety. We synthesized natural and artificial scytophycin analogs and evaluated their cytotoxicity, elucidating that the combination of the macrolactone and side-chain moieties is important to the strong cytotoxicity of scytophycins and there is little difference between analogs with the different macrolactone moiety.