Biological evaluation of bishydroxymethyl-substituted cage dimeric 1,4-dihydropyridines as a novel class of p-glycoprotein modulating agents in cancer cells.

A series of N-substituted cage dimeric 1,4-dihydropyridines 3a-e was evaluated as inhibitors of membrane efflux pump P-glycoprotein (P-gp) in multidrug resistant (mdr) cancer cells. Structure-activity relationships (SAR) and cytotoxic properties are discussed. Effective concentrations for overcoming mdr have been demonstrated in competition studies with the P-gp substrate epirubicin.