Synthesis and biological evaluation of 4-arylcoumarin analogues of combretastatins.

ABSTRACT

A series of A-ring polymethoxylated neoflavonoids was prepared by ligand coupling reactions involving either Suzuki or Stille reactions. Cytotoxicity studies indicated a potent activity against a CEM leukemia cell line for the compounds presenting a substitution pattern related to that of combretastatin A-4. The two compounds having a 3'-OH and a 4'-OCH(3) substituents on the 4-phenyl B-ring have no effect on human topoisomerases I and II but potently inhibit, in vitro, microtubule assembly. At the cell level, the active compounds were characterized as proapoptotic agents, but they can also trigger cell death via a nonapoptotic pathway.