Synthesis, cytotoxic evaluation, and molecular docking study of 4,5-diaryl-thiazole-2-thione analogs of combretastatin A-4 as microtubule-binding agents

摘要

A series of combretastatin A-4 analogs in which m-olefinic bond replaced by thiazole ring were prepared by reaction of alpha-bromo-l,2-(p-substituted)diaryl-1-ethanones and dithiocarbamate derivatives. The cyto-toxicity of these compounds was determined against three cancer cell lines (HT-29), (MCF-7), (AGS) as well as fibroblastic cell line (NIH-3T3) using MTT assay. Inhibition of tubulin polymerization for some potent compounds was evaluated. These biological studies proved that 6j and 60 were the most potent compounds in this series. Furthermore 2-(methylthio)-substituted compounds show moderate or no activity. Docking studies involving 6j and 60 demonstrated that this analogs could be successfully docked in the colchicine binding site of alpha,beta-tubulin.