Design, synthesis, cytotoxic evaluation and tubulin inhibitory activity of 4-aryl-5-(3,4,5-trimethoxyphenyl)-2-alkylthio-1H-imidazole derivatives
Design, synthesis, cytotoxic evaluation and tubulin inhibitory activity of 4-aryl-5-(3,4,5-trimethoxyphenyl)-2-alkylthio-1H-imidazole derivatives
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DOI：
10.1016/j.bmc.2013.03.011
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发表时间：
2013-05-15
影响因子：
3.5
通讯作者：
Shafiee, Abbas
中科院分区：
文献类型：
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作者：
Assadieskandar, Amir;Amini, Mohsen;Shafiee, Abbas
合成了一系列新的4-芳基-5-（3，4，5-三甲氧基苯基）-2-烷硫基-1H-咪唑类化合物，并评价了它们对HT-29，MCF-7，NIH-3 T3，AGS四种不同细胞系的体外细胞毒活性。化合物6 g在A环上带有3，4，5-三甲氧基苯基部分，在B环上带有4-甲氧基取代基，对所有细胞系显示出强的细胞毒活性。流式细胞仪分析和微管聚合实验证实，该化合物的细胞毒活性与抑制微管聚合有关。分子模拟研究显示，化合物6 g可以通过与Thr α 179和Cys β 241的氢键相互作用与α，β-微管蛋白的秋水仙碱结合位点强烈结合。(C)2013爱思唯尔有限公司保留所有权利。
A new series of 4-aryl-5-(3,4,5-trimethoxyphenyl)-2-alkylthio-1H-imidazoles were synthesized and their cytotoxic activities in vitro against four different cell lines (HT-29, MCF-7, NIH-3T3, AGS) were evaluated. Compound 6g bearing 3,4,5-trimethoxyphenyl moiety on ring A and 4-methoxy substituent on ring B displayed potent cytotoxic activity against all cell lines. Flow cytometry analysis and microtubule polymerization assay confirmed that cytotoxic activities of this compound were related to inhibitory effect against microtubules polymerization. Molecular modeling studies revealed that compound 6g could strongly bind to the colchicine binding site of alpha,beta-tubulin through hydrogen bond interactions with Thr alpha 179 and Cys beta 241. (C) 2013 Elsevier Ltd. All rights reserved.