Study on Molecular Mechanism of Cytotoxicity of Marine Natural Products

研究了海洋大环内酯类化合物阿普利氨酸A抗肿瘤的分子机制。利用化学探针发现阿普氨酸A与肌动蛋白和微管蛋白结合形成三元配合物。结果，阿普氨酸a抑制微管蛋白聚合，诱导不规则的多极纺锤体结构，抑制细胞周期在m期的进展，并诱导细胞凋亡。以Wittig反应和烯丙醇的选择性酶解为关键步骤，合成了具有细胞毒性的海洋大环内酯类物质双甾体A。

The molecular mechanism of antitumor activity of aplyronine A, a marine macrolide, has been investigated. Using chemical probes aplyronine A was found to bind to actin and tubulin to form a ternary complex.As a result, aplyronine A inhibits tubulin polymerization, induces irregular, multipolar spindle structures, inhibits cell-cycle progression in M-phase, and induces apoptosis.Total synthesis of biselide A, a cytotoxic marine macrolide, was achieved by using Wittig reaction and sereoselective enzymatic hydrolysis of allylic alcohol as key steps.