New [1,4]Dihydropyridines for P-gp Mediated Efflux of Anticancer Drugs

Cancer is a leading cause of death these days which require chemotherapeutic drugs for treatment. Although various chemotherapeutic agents have been developed, still there is no successful treatment against multidrug resistance acquired by the cancer cells due to high P-gp expression in the cell walls. In the effort to synthesize new compounds that overcome multidrug resistance, we have synthesized a novel series of N-unsubstituted and N-substituted [1,4]-DHPs and evaluated these derivatives for P-gp inhibitory activity using Rhodamine B as P-gp substrate. From the in vitro assay, it has been found that N-substituted [1,4]-DHPs exhibits improved activity then N-unsubstituted compounds. The aliphatic substitution at 1st position of unsymmetrical [1,4]-DHPs resulted in good fluorescence uptake.