新型甾体血管新生抑制剂Cortistatin的结构、生物活性与合成

由于肿瘤的生长与转移高度依赖于血管新生,因此发现和发明新型血管新生抑制剂对肿瘤疾病治疗有重要意义.以Cortistatin A为代表的Cortistatin类海洋天然产物是一类化学结构新颖、具有显著血管新生抑制作用的甾体化合物.它们具有9-(10,19)-abeo-雄甾烷骨架和氧原子桥连七元B环结构,Cortistatin A对人脐静脉内皮细胞(HUVEC)增殖具有nmol/L级的抑制活性和相对其他细胞系大于3300的选择性指数.综述了Cortistatin及其类似物自发现来两年期间的合成进展情况.

Structure, Bioactivity and Synthesis of Cortistatins, a New Kind of Steroidal Angiogenesis Inhibitors

The discovery and invention of new type of anti-angiogenesis agents are very important for the treatment of a variety of tumors due to a fact that growth and metastasis of tumor highly depended upon angiogenesis. Cortistatin A and its analogues are a new kind of steroidal alkaloids with 9-(10,19)-abeo-androstane skeleton and a bridged seven-membered B ring of marine origin. Cortistatin A shows cytostatic anti-proliferative activity against human umbilical vein endothelial cell (HUVEC) at very wide range concentrations (100 pmol/L to 1 μmol/L), in which the selective index is more than 3300-fold higher in comparison with those of several other cell lines. This review summarizes the synthetic progress of cortistatin A and its analogues since their discovery in 2006～2007.