1-脱氧-9-(R)-二氢紫杉烷类似物的合成、生物活性及微管蛋白结合模式

Synthesis, biological activity and tubulin binding poses of 1-deoxy-9-(R)-dihydrotaxane analogs.

作者信息

Yuan Tian-Hai, Jiang Yi, Wang Xiao-Hong, Wang Dian-Long, Bannerjee Abhijit, Bane Susan, Snyder James P, Lin Hai-Xia

机构信息

Department of Chemistry, Shanghai University, Shanghai 200444, China.

出版信息

Bioorg Med Chem Lett. 2009 Feb 15;19(4):1148-51. doi: 10.1016/j.bmcl.2008.12.091. Epub 2008 Dec 27.

DOI:10.1016/j.bmcl.2008.12.091

PMID:19136258

Abstract

1-Deoxy-9alpha-dihydrotaxane analogs 9 and 10 were semi-synthesized from 1-deoxybaccatin VI, isolated from Taxus mairei, and tested for cytotoxic activity. Taxane 9 is 10-fold less cytotoxic than paclitaxel, while 10 is equally active. In the tubulin polymerization assay (ED(50) values), 10 is 4-fold less effective than paclitaxel, but 3-fold superior to 9. These observations can be explained by analysis of the corresponding taxane/beta-tubulin complexes.

摘要

1-脱氧-9α-二氢紫杉烷类似物9和10由从南方红豆杉中分离得到的1-脱氧巴卡亭VI半合成，并对其细胞毒性活性进行了测试。紫杉烷9的细胞毒性比紫杉醇低10倍，而10具有同等活性。在微管蛋白聚合试验（半数有效剂量值）中，10的效力比紫杉醇低4倍，但比9高3倍。通过分析相应的紫杉烷/β-微管蛋白复合物可以解释这些观察结果。