Design, synthesis, biochemical, and biological evaluation of nitrogen-containing trifluoro structural modifications of combretastatin A-4

A series of nitrogen-containing fluoro combretastatin structural modifications have been synthesized and evaluated for potential anti-cancer activity. A new trifluorinated amino-combretastatin analogue, ( Z)-2-(4′-methoxy-3′-aminophenyl)-1-(3,4,5-trifluorophenyl)ethene, prepared by chemical synthesis, was found to be a potent inhibitor of tubulin assembly (IC 50 = 2.9 μM), and cytotoxic against selected human cancer cell lines. This new lead compound is among the most active from a group of related structural modifications.