부산대학교 도서관

• An efficient Palladium-catalyzed C O cross-coupling reaction between bromo-chalcones and ethyl acetohydroxamate (EAcHO) has been developed. • t BuXPhos (L7), and cataCXium®PIntB (L16) ligands were found to be effective towards the Pd-catalyzed coupling reaction. • The coupled products were screened for their antiplasmodial activity against Plasmodium falciparum (3D7), and the selected active molecules were tested for their cytotoxic effect against HepG2 Cells. • The chalcone 19 was found to be a most active molecule with an IC 50 value of 6 μg/mL against Plasmodium falciparum (3D7) and the selectivity index was >16.7 against HepG2 Cell lines. 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 [3H] 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. [ABSTRACT FROM AUTHOR]