Synthesis and biological evaluation of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones as combretastatin analogs
Synthesis and biological evaluation of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones as combretastatin analogs
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DOI：
10.1016/j.ejmech.2013.10.046
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发表时间：
2013-12-01
影响因子：
6.7
通讯作者：
Emami, Saeed
中科院分区：
文献类型：
--
作者：
Banimustafa, Mandana;Kheirollahi, Asma;Emami, Saeed
设计了一系列3-（三甲氧基苯基）-2（3 H）-噻唑硫酮5作为考布他汀A-4（CA-4）的新杂环类似物。事实上，CA-4的烯属核心结构已被2（3 H）噻唑取代。制备化合物5的一般合成策略是基于N-（三甲氧基苯基）二硫代氨基甲酸三乙基铵与适当的苯甲酰甲基卤之间的环化缩合反应。3-（三甲氧基苯基）-2（3 H）-噻唑硫酮5对人癌细胞系T47 D、MCF-7和MDA-MB-231的细胞毒活性评价表明，4-甲基类似物5 f对所有细胞系显示出最高的活性。化合物5 f对非肿瘤细胞MRC-5无明显毒性，对癌细胞有明显的选择性。生物测定结果表明，代表性化合物5 f解聚微管蛋白，抑制细胞增殖，并诱导癌细胞凋亡。(C)2013年Elsevier Masson SAS。All rights reserved.
A series of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones 5 were designed as new heterocyclic analogs of combretastatin A-4 (CA-4). Indeed, the olefinic core structure of CA-4 has been replaced by 2(3H)thiazole thione. The general synthetic strategy to prepare compounds 5 was based on the cyclocondensation reaction between triethylammonium N-(trimethoxyphenyl)dithiocarbamate and appropriate phenacyl halide. The cytotoxic activity evaluation of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones 5 against human cancer cell lines T47D, MCF-7 and MDA-MB-231 demonstrated that 4-methyl analog 5f showed the highest activity against all cell lines. Compound 5f had no significant toxicity towards non-tumoral cells MRC-5 and its cytotoxicity was apparently selective for cancer cells. The results of bioassays showed that the representative compound 5f depolymerized tubulin, inhibited cell proliferation, and induced apoptosis in cancer cells. (C) 2013 Elsevier Masson SAS. All rights reserved.