Synthesis, molecular modeling and biological evaluation of dithiocarbamates as novel antitubulin agents

A series of novel dithiocarbamate compounds with the chalcone scaffold have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and antitubulin polymerization inhibitors. Compound 2n showed the most potent biological activity in vitro, which inhibited the growth of MCF-7 cells with IC50 of 0.04 ± 0.01 μM and the polymerization of tubulin with IC50 of 6.8 ± 0.6 μM. To understand the tubulin–inhibitor interaction and the selectivity of the most active compound towards tubulin, molecular modeling studies were performed to dock compound 2n into the colchicine binding site, which suggested probable inhibition mechanism.

Compound 2n showed the most potent biological activity in vitro, which inhibited the growth of MCF-7 human breast carcinoma cells with IC50 of 0.04 ± 0.01 μM and the polymerization of tubulin with IC50 of 6.8 ± 0.6 μM. To understand the tubulin–inhibitor interaction and the selectivity of the most active compound towards tubulin, molecular modeling studies were performed to dock compound 2n into colchicine binding site and this study provided probable inhibition mechanism. The result indicated that compound 2n was a potent inhibitor of tubulin polymerization.Figure optionsDownload as PowerPoint slide