Arylthioindoles, potent inhibitors of tubulin polymerization: structure-activity relationships and molecular modeling studies

Tubulin is a very important target for anticancer therapy. Recently, we reported several arylthioindoles with an excellent biological activity as inhibitors of tubulin polymerization and of some carcinoma cells.1,2 To investigate the structural basis of the SAR that emerged from the biological results, we carried out docking and molecular dynamics studies. Ethyl 5-methoxy-3-[(3,4,5-trimethoxyphenyl)thio]-1H-indole-2-carboxylate showed a very interesting binding mode into colchicine binding site of tubulin. References 1] De Martino, G.; La Regina, G.; Coluccia, A. et al. J. Med. Chem. 2004, 47, 6120-6123. 2] De Martino, G.; Michael C. Edler, M. C.; La Regina, G. et al. J. Med. Chem. 2006, 49, 947-954.