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

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 ag...

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Bibliographic Details
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
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Summary:	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.
ISSN:	0250-7005