Novel imidazole-based combretastatin A-4 analogues: Evaluation of their in vitro antitumor activity and molecular modeling study of their binding to the colchicine site of tubulin

The in vitro antitumor activity of novel combretastatin-like 1,5- and 1,2-diaryl-1H-imidazoles was evaluated against the NCI 60 human tumor cell lines panel. Compounds 2d and 2g proved to be more cytotoxic than CA-4 in tests involving their evaluation over a 10−4–10−8 range. Docking experiments showed a good correlation between the MG_MID Log GI50 values of all these compounds and their calculated interaction energies with the colchicine binding site of αβ-tubulin.

The results of docking experiments aimed at calculating the interaction energies of a variety of 1,5- and 1,2-diaryl-1H-imidazoles with the colchicine binding site of tubulin are reported along with their in vitro antitumor activity data.Figure optionsDownload as PowerPoint slide