Imidazolone-amide bridges and their effects on tubulin polymerization in cis-locked vinylogous combretastatin-A4 analogues: Synthesis and biological evaluation
Imidazolone-amide bridges and their effects on tubulin polymerization in cis-locked vinylogous combretastatin-A4 analogues: Synthesis and biological evaluation
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咪唑酮-酰胺桥及其对顺锁插烯考布他汀-A4类似物中微管蛋白聚合的影响：合成和生物学评价
DOI：
10.1016/j.bmc.2011.03.068
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发表时间：
2011-06-01
影响因子：
3.5
通讯作者：
Zhou, You-Jun
中科院分区：
文献类型：
--
作者：
Li, Yao-Wu;Liu, Jia;Zhou, You-Jun
合成了一系列以咪唑酮酰胺取代顺式烯烃桥的新型comretataatin-A4类似物，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。含3‘-氨基-4’-OCH3、4‘-CH3和3’-CH3取代的1-苯基B环的化合物10、9b和9c具有最好的生物活性。通过分子对接获得了这些化合物与微管蛋白的结合方式，可以解释化合物的构效关系。本研究为新型抗肿瘤药物的开发提供了一种新的结构类型。(C)2011爱思唯尔有限公司。保留所有权利。
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. (C) 2011 Elsevier Ltd. All rights reserved.