Discovery of benzochromene derivatives first example with dual cytotoxic activity against the resistant cancer cell MCF-7/ADR and inhibitory effect of the P -glycoprotein expression levels.

A series of 1 H -benzo[ f ]chromene moieties ( 4a-z ) were synthesised under Ultrasonic irradiation and confirmed with spectral analyses. Derivative 4i solely possessed an X-ray single crystal. The anti-proliferative efficacy of the desired molecules has been explored against three cancer cells: MCF-7, HCT-116, and HepG-2 with the cytotoxically active derivatives screened against MCF-7/ADR and normal cells HFL-1 and WI-38. Furthermore, compounds 4b-d , 4k , 4n , 4q , and 4w , which possessed good potency against MCF-7/ADR, were tested as permeability glycoprotein ( P- glycoprotein [ P -gp]) expression inhibitors. The attained data confirmed that 4b-d , 4q , and 4w exhibited strong expression inhibition against the P- gp alongside its cytotoxic effect on MCF-7/ADR. The western blot results and Rho123 accumulation assays showed that compounds 4b-d, 4q , and 4w effectively inhibited the P -gp expression and efflux function. Meanwhile, 4b-d , 4q , and 4w induced apoptosis and accumulation of the treated MCF-7/ADR cells in the G1 phase and 4k and 4n in the S phase of the cell cycle.