3,5-dibenzoyl-1,4-dihydropyridines:: Synthesis and MDR reversal in tumor cells

Fifteen 4-phenyl-3.5-dibenzoyl-1,4-dihydropyridines (BzDHPs) (1-15) substituted at the 4-phenyl ring were synthesized and compared to their cytotoxic activity and multidrug resistance (MDR)-reversing activity in in vitro assay systems. Among them, 2-CF3 (5) (IC50 =8.7 muM), 2-Cl (11) (IC50 = 7.0 muM) and 3-Cl (12) (IC50 = 7.0 muM) derivatives showed the highest cytotoxic activity against human oral squamous carcinoma (HSC-2) cells. The activity of P-glycoprotein (Pgp) responce for MDR in tumor cells was reduced by some of derivatives (3, 4, 8, 12), verapamil (VP) and nifedipine (NP). These data suggest that 3,5-dibenzoyl-4-(3-chlorophenyl)-1,4-dihydro-2,6-dimethylpyridine (12) can be recommended as a new drug candidate for MDR cancer treatment. (C) 2002 Elsevier Science Ltd. All rights reserved.