title: 3,5-dibenzoyl-1,4-dihydropyridines: synthesis and MDR reversal in tumor cells.
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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 350-0295, Saitama, Japan. kawasema@josai.ac.jp
authors.forename: Masami
authors.initials: M
authors.lastname: Kawase
authors.forename: Anamik
authors.initials: A
authors.lastname: Shah
authors.forename: Harsukh
authors.initials: H
authors.lastname: Gaveriya
authors.forename: Noboru
authors.initials: N
authors.lastname: Motohashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Andreas
authors.initials: A
authors.lastname: Varga
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnár
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004095:Dihydropyridines