Arylthioindoles, Potent Inhibitors of Tubulin Polymerization

Several arylthioindoles had excellent activity as inhibitors both of tubulin polymerization and of the growth of MCF-7 human breast carcinoma cells. Methyl 3-(3,4,5-trimethoxyphenyl)thio-5-methoxy-1H-indole-2-carboxylate (21), the most potent derivative, showed IC(50) = 2.0 microM, 1.6 times more active than colchicine and about as active as combretastatin A-4 (CSA4). Compound 21 inhibited the growth of the MCF-7 cells at IC(50) = 13 nM. Colchicine and CSA4 had 13 nM and 17 nM IC(50) values, respectively, with these cells.