Synthesis of novel chalcones through palladium-catalyzed C O cross-coupling reaction of bromo-chalcones with ethyl acetohydroxamate and their antiplasmodial evaluation against Plasmodium falcipuram in vitro

Abstract An efficient method for palladium-catalyzed C O cross-coupling of ethyl acetohydroxamate (EAcHO) with 4-bromo-chalcones has been developed to synthesize novel chalcones. The two supporting ligands, namely t BuXPhos ( L7 ), and cataCXium®PIntB ( L16 ) were found to be effective ligands towards the Pd-catalyzed C O cross-coupling reaction to afford the desired product in moderate to excellent yields (50–99%). The coupled products were screened for in vitro blood stage antiplasmodial activity against Plasmodium falciparum (3D7) using the [ 3 H] hypoxanthine incorporation inhibition assay. Of the twenty two compounds screened, eleven showed good antiplasmodial activity with IC 50 values ranging from 6–16 μg/mL. The selected active molecules 11 , 16 , 22 , (IC 50 12 μg/mL) and 19 (IC 50 6 μg/mL) were studied for their cytotoxic effect against HepG2 Cells (human hepatocellular liver carcinoma cell lines), showing the selectivity index (SI) values are greater than 4 except chalcone 22 . Our result demonstrates a methodology for synthesizing novel chalcones as a new class of antiplasmodial agent.