Synthesis and biological evaluation of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones as combretastatin analogs

被引：48

作者：

Banimustafa, Mandana ^{[1
]}

Kheirollahi, Asma ^{[2
]}

Safavi, Maliheh ^{[3
]}

Ardestani, Sussan Kabudanian ^{[3
]}

Aryapour, Hassan ^{[4
]}

Foroumadi, Alireza ^{[5
]}

Emami, Saeed ^{[6
,7
]}

机构：

[1] Mazandaran Univ Med Sci, Fac Pharm, Student Res Comm, Sari 48175861, Iran

[2] Univ Tehran Med Sci, Sch Med, Dept Clin Biochem, Tehran, Iran

[3] Univ Tehran, Inst Biochem & Biophys, Dept Biochem, Tehran, Iran

[4] Golestan Univ, Dept Biol, Fac Sci, Gorgan, Iran

[5] Univ Tehran Med Sci, Pharmaceut Sci Res Ctr, Tehran, Iran

[6] Mazandaran Univ Med Sci, Fac Pharm, Dept Med Chem, Sari 48175861, Iran

[7] Mazandaran Univ Med Sci, Fac Pharm, Pharmaceut Sci Res Ctr, Sari 48175861, Iran

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 70卷

关键词：

Anticancer activity; Cytotoxicity; Combretastatin analogs; 2(3H)-Thiazole thiones; Thiazolidine-2-thione; Tubulin polymerization; COLCHICINE BINDING-SITE; ANTINEOPLASTIC AGENTS; TUBULIN POLYMERIZATION; ANTIMITOTIC AGENTS; DERIVATIVES; CANCER; CELLS; A-4; CYTOTOXICITY; INHIBITORS;

D O I：

10.1016/j.ejmech.2013.10.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 Indeed, the olefinic core structure of CA-4 has been replaced by 2(3H)thiazole thione.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.

引用

页码：692 / 702

页数：11

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