Bcl-2蛋白天然产物抑制剂的研究进展

Progress in natural product inhibitors of Bcl-2 protein

研究表明Bcl-2蛋白过度表达会阻止正常的细胞凋亡,是肿瘤产生及发生耐药的重要原因之一。近几年,其抗肿瘤小分子抑制剂的研究逐渐成为热点。研究者发现了一些不同结构类型的抑制剂,其中天然产物占很大比重。文中对已发现的Bcl-2蛋白天然产物抑制剂(包括棉酚、红棓酚、茶多酚、抗菌霉素A3)的结构、生物活性、与蛋白结合模式及结构改造等方面进行了系统的综述,着重介绍了几类经结构改造后活性较好的棉酚衍生物(ApoGossypol,TW37,TM-1206,BI-33),期望对从天然产物中寻找Bcl-2抑制剂以及合理设计抑制剂提供帮助。

Studies have shown that the overexpression of Bcl-2 protein, which can inhibit the normal cellular apoptosis, is one of the important factors in tumor progression and resistance to therapeutic agents. In recent years, the research on anti-tumor small molecule inhibitors of Bcl-2 is becoming a hot spot. Some small molecule inhibitors with diverse chemical structures including a large partition of natural products have been found. This paper systematically reviewed the progress in structures, biological activity, protein-binding modes, and structural modification of the natural product inhibitors （including gossypol, purpurogallin, tea polyphenols and antimycin A3 ）. We emphasize several gossypol derivatives （ApoGossypol, TW37, TM-1206, BI-33） that have been modified and have good bioactivity. It is expected that the review will provide guidance to find Bcl-2 inhibitor from natural products, and to rationally design Bcl-2 inhibitors.