5-Amino-2-Aroylquinolines as Highly Potent Tubulin Polymerization Inhibitors

A series of aroylquinoline derivatives were synthesized and evaluated for anticancer activity. 5-Amino-6-methoxy-2-aroylquinoline 15 showed more potent antiproliferative activity (IC₅₀ values ranging from 0.2 to 0.4 nM) as compared to 1a (combretastatin A-4) (IC₅₀ = 1.9−835 nM) against various human cancer cell lines and a MDR-resistant cancer cell line. Compound 15 (IC₅₀ = 1.6 μM) exhibited more potent inhibition of tubulin polymerization than 1a (IC₅₀ = 2.1 μM) and showed strong binding property to the colchicine binding site of microtubules.