Synthesis of 9-Hydroxy-1 H -Benzo[ f ]chromene Derivatives with Effective Cytotoxic Activity on MCF7/ADR, P -Glycoprotein Inhibitors, Cell Cycle Arrest and Apoptosis Effects.

β -Enaminonitriles bearing 9-hydroxy-1 H -benzo[ f ]chromene moiety was synthesized. The targeted compounds were evaluated for their anti-proliferative activity against three human tumor cell lines, PC-3, SKOV-3 and HeLa, and the active cytotoxic compounds were further evaluated against cancer cells, MCF-7/ADR, and two normal cell lines, HFL-1 and WI-38. Few compounds were assigned to be the most potent derivatives against PC-3, SKOV-3 and HeLa cell lines in comparison with Vinblastine and Doxorubicin. Several compounds possessed a relatively good potency against MCF-7/ADR cells as compared with Doxorubicin and were tested as a P -gp inhibitor. Moreover, the halogenated substituents, 2,4-F 2 , 2,3-Cl 2 , 2,5-Cl 2 and 3,4-Cl 2; have good potency against P -gp-mediated MDR in MCF-7/ADR as compared with Doxorubicin. Meanwhile, Rho123 accumulation assays revealed that few compounds effectively inhibited P -pg and efflux function. In addition, certain derivatives induced apoptosis and an accumulation of the treated MCF-7/ADR cells in the G1, S and G1/S phases.