Design And Synthesis Of CA-4 Flurinated Analogues As Tubulin Inhibitor

Combretastatin A-4 (CA-4), first isolated from the African willow tree combretum caffrum, is a tubulin polymerization inhibitor. It can inhibit tubulin polymerization to prevent tumor blood flow binding to the colchicine site. Due to the structure of CA-4 exists trans inactive and cis unstable, which limit its application in clinic. So the structural transformation is needed.In this paper, CA-4 fluorinated analogues have been designed and synthesized through computer aided and chemical synthesis. The structure characterization and antitumor activity in vitro of these compounds were studied. In addition, molecular modeling indicated the binding site of CA-4 and its derivatives on fungal tubulin. Antifungal activity of them were tested in vitro.