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

Abstract

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 Indeed, the olefinic core structure of CA-4 has been replaced by 2(3H)-thiazole thione.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

• Authors: Mandana Banimustafa, Asma Kheirollahi, Maliheh Safavi, Sussan Kabudanian Ardestani, Hassan Aryapour, Alireza Foroumadi, Saeed Emami
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 70 Pg. 692-702 ( 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 24219991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• 3-(trimethoxyphenyl)-2(3H)-thiazole thione
• Antineoplastic Agents
• Bibenzyls
• Thiazoles
• combretastatin

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Bibenzyls (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• MCF-7 Cells
• Molecular Structure
• Structure-Activity Relationship
• Thiazoles (chemical synthesis, chemistry, pharmacology)