Tumour-specific cytotoxicity and MDR-reversal activity of dihydropyridines.
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.
Engi
Helga
H
Department of Medical Microbiology and Immunobiology, Albert Szent-Györgyi Medical Centre, University of Szeged, H-6720 Szeged, Hungary.
Sakagami
Hiroshi
H
Kawase
Masami
M
Parecha
Alpesh
A
Manvar
Dinesh
D
Kothari
Himanshu
H
Adlakha
Priti
P
Shah
Anamik
A
Motohashi
Noboru
N
Ocsovszki
Imre
I
Molnár
Joseph
J
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004095:Dihydropyridines