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

Bioorg Med Chem. 2002 Apr;10(4):1051-5. doi: 10.1016/s0968-0896(01)00363-7.

Abstract

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 microM), 2-Cl (11) (IC50=7.0 microM) and 3-Cl (12) (IC50=7.0 microM) derivatives showed the highest cytotoxic activity against human oral squamous carcinoma (HSC-2) cells. The activity of P-glycoprotein (Pgp) response 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • Dihydropyridines / chemical synthesis
  • Dihydropyridines / pharmacology*
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Drug Screening Assays, Antitumor
  • Humans
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Dihydropyridines