title: Tumour-specific cytotoxicity and MDR-reversal activity of dihydropyridines.
abstract: The ability of 41 1,4-diphenyl-1,4-dihydropyridine derivatives to inhibit the transport activity of P-glycoprotein were studied by flow cytometry in a multidrug-resistant human colon cancer cell line (COLO320) and in human mdr1 gene-transfected mouse lymphoma cells (L 5178 Y). The cytotoxicities of these compounds were also examined against human normal and cancer cell lines. The majority of the tested compounds proved to be effective inhibitors of rhodamine 123 outward transport, but their cytotoxicities were not negligible. Some dihydropyridine derivatives displayed cytotoxic activity against four human oral tumour cell lines and against three normal human oral cell lines. There was no clear-cut relationship between the multidrug-resistance activity or cytotoxicity and the chemical structures of the compounds. New ring substituents could prevent the oxidation of the ring of the aromatic compound.
authors.affiliation: Department of Medical Microbiology and Immunobiology, Albert Szent-Györgyi Medical Centre, University of Szeged, H-6720 Szeged, Hungary.
authors.forename: Helga
authors.initials: H
authors.lastname: Engi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Masami
authors.initials: M
authors.lastname: Kawase
authors.forename: Alpesh
authors.initials: A
authors.lastname: Parecha
authors.forename: Dinesh
authors.initials: D
authors.lastname: Manvar
authors.forename: Himanshu
authors.initials: H
authors.lastname: Kothari
authors.forename: Priti
authors.initials: P
authors.lastname: Adlakha
authors.forename: Anamik
authors.initials: A
authors.lastname: Shah
authors.forename: Noboru
authors.initials: N
authors.lastname: Motohashi
authors.forename: Imre
authors.initials: I
authors.lastname: Ocsovszki
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnár
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002460:Cell Line; D045744:Cell Line, Tumor; D004095:Dihydropyridines / Q000493:pharmacokinetics / Q000633:toxicity*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D014162:Transfection
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004095:Dihydropyridines