2-amino-3,4,5-trimethoxybenzophenones as potent tubulin polymerization inhibitors

Abstract

A series of novel 2-amino-3,4,5-trimethoxybenzophenone analogues exhibited excellent activity as tubulin polymerization inhibitors by targeting the colchicine binding site of microtubules. The lead compound 17 exhibited an IC50 value of 1.6 μM, similar to that of combretastatin A-4 (IC50=1.9 μM). It also displayed remarkable anti-proliferative activity, with IC50 values ranging from 7-16 nM against a variety of human cancer cell lines and one MDR(+) cancer cell line. SAR information indicated that the introduction of an amino group at the C2 position of benzophenone ring A and the C3' position of benzophenone ring B play important roles in maximizing activity.