Add time:08/14/2019 Source:sciencedirect.com
An efficient method for palladium-catalyzed CO cross-coupling of Ethyl acetohydroxamate (cas 10576-12-2) (EAcHO) with 4-bromo-chalcones has been developed to synthesize novel chalcones. The two supporting ligands, namely tBuXPhos (L7), and cataCXium®PIntB (L16) were found to be effective ligands towards the Pd-catalyzed CO 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 IC50 values ranging from 6–16 μg/mL. The selected active molecules 11, 16, 22, (IC50 12 μg/mL) and 19 (IC50 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.
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