Overexpression of P-glycoprotein (P-gp) is one of the major problems to successful cancer chemotherapy. To find novel effective P-gp inhibitors, a series of bifendate–chalcone hybrids were synthesized and evaluated. Among them, the most active compound 8g had little intrinsic cytotoxicity (IC50> 200μM), and could increase accumulation of Rhodamine 123 in K562/A02 cells more potently than bifendate and verapamil (VRP) by inhibiting P-gp efflux ...