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

• Published in: Anticancer research Vol. 20; no. 1A; p. 373
• Main Authors: Shah, A, Gaveriya, H, Motohashi, N, Kawase, M, Saito, S, Sakagami, H, Satoh, K, Tada, Y, Solymosi, A, Walfard, K, Molnar, J
• Format: Journal Article
• Language: English
• Published: Greece 01-01-2000
• Subjects: Antineoplastic Agents - pharmacology; Calcium Channel Blockers - pharmacology; Carcinoma, Squamous Cell - pathology; Chemical Phenomena; Chemistry, Physical; Dihydropyridines - chemical synthesis; Dihydropyridines - chemistry; Dihydropyridines - pharmacology; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Fluorescent Dyes - metabolism; HL-60 Cells - drug effects; Humans; Molecular Structure; Rhodamine 123 - metabolism; Structure-Activity Relationship; Tumor Cells, Cultured - drug effects
• ISSN: 0250-7005

Eleven 4-phenyl-3,5-diacetyl-1,4-dihydropyridines (AcDHPs) [G1-11] substituted at the phenyl ring were synthesized and compared for their cytotoxic activity and multidrug resistance (MDR)-reversing activity in in vitro assay systems. Among them, compound [G7] showed the highest cytotoxic activity against human promyelocytic leukemia HL-60 and human squamous cell carcinoma HSC-2 cells. However, no compounds tested produced radicals at pH 7.4-12.5. The activity of P-glycoprotein (Pgp) responsible for MDR in tumor cells was reduced by compounds [G2, 3, 6, 5, 8, 1, 11], verapamil [VP] and nifedipine [NP]. However, compounds [G4, 7, 10] were hardly active while G9 did not show a MDR reversing effect at 2.0-20.0 micrograms/mL. These data show a relationship between chemical structures and MDR-reversing effect on tumor cells.