Air Force General Hospital, Beijing 100036, China.
Bioorg Med Chem. 2011 Jun 1;19(11):3579-84. doi: 10.1016/j.bmc.2011.03.068. Epub 2011 Apr 3.
A series of novel combretastatin-A4 analogues in which the cis-olefinic bridge is replaced by an imidazolone-amide were synthesized, and their cytotoxicity and tubulin-polymerization inhibitory activities were evaluated. These compounds appear to be potential tubulin-polymerization inhibitors. Compounds 10, 9b and 9c, bearing 3'-NH₂-4'-OCH₃, 4'-CH₃ and 3'-CH₃-substituted 1-phenyl B-ring, confer optimal bioactivity. The binding modes of these compounds to tubulin were obtained by molecular docking, which can explain the compounds' structure-activity relationship. The studies presented here provide a new structural type for the development of novel antitumor agents.
合成了一系列新型考布他汀 A4 类似物，其中顺式烯烃桥被咪唑啉酰胺取代，并对其细胞毒性和微管蛋白聚合抑制活性进行了评价。这些化合物似乎是潜在的微管蛋白聚合抑制剂。化合物 10、9b 和 9c 带有 3'-NH₂-4'-OCH₃、4'-CH₃ 和 3'-CH₃ 取代的 1-苯基 B 环，具有最佳的生物活性。通过分子对接获得了这些化合物与微管蛋白的结合模式，这可以解释化合物的构效关系。本文的研究为开发新型抗肿瘤药物提供了一种新的结构类型。
