2-Amino-3,4,5-Trimethoxybenzophenones as Potent Tubulin Polymerization Inhibitors

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 1.6μM, similar to that of combretastatin A-4 (IC₅₀=1.9μM). It also displayed remarkable anti-proliferative activity, with IC₅₀ values ranging from 7-16nM 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 ringA and the C3' position of benzophenone ringB play important roles in maximizing activity.