Anti-cancer activity of m-carborane-containing trimethoxyphenyl derivatives through tubulin polymerization inhibition
Anti-cancer activity of m-carborane-containing trimethoxyphenyl derivatives through tubulin polymerization inhibition
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DOI：
10.1016/j.bmc.2019.02.018
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发表时间：
2019-03-15
影响因子：
3.5
通讯作者：
Ohta, Kiminori
中科院分区：
文献类型：
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作者：
Kaise, Asako;Endo, Yasuyuki;Ohta, Kiminori
从随机筛选的硼化合物文库中鉴定出含m-碳硼烷的化合物1a为细胞生长抑制剂。由于1a是两个手性碳的非对映体混合物，我们设计了非手性衍生物2-4，并研究了苯环上甲氧基的构效关系。与先导化合物1a相比，3,4,5-三甲氧基苯甲酰基衍生物2a和3,4,5-三甲氧基苯甲酰基衍生物3a对人乳腺癌细胞株MDA-MB-453具有更强的抗癌活性。化合物3a以剂量依赖的方式抑制微管蛋白聚合。
m-Carborane-containing compound 1a was identified as a cell growth inhibitor from a random screening of a boron compound library. As 1a is a mixture of diastereomers due to the presence of two chiral carbons, we designed achiral derivatives 2-4 and studied the structure-activity relationships of the methoxy groups on the benzene ring. 3,4,5-Trimethoxybenzyl derivative 2a and 3,4,5-trimethoxybenzoyl derivative 3a showed more potent anti-cancer activity against the human breast cancer cell line MDA-MB-453 than lead compound 1a. Compound 3a inhibited tubulin polymerization in a dose-dependent manner.