Substituted pyridazino[3,4-b][1,5]benzoxazepin-5(6H)ones as multidrug-resistance modulating agents.
Pyridazino[3,4-b][1,5]benzoxazepin-5(6H)ones substituted with propylene-linked basic side chains were synthesized and investigated for the ability to reverse multidrug resistance (MDR) at vincristine-pretreated HeLa-MDR1 cells. The substances were found to be effective chemosensitizers with activity comparable to that of the known MDR modulator verapamil. The observed antiproliferative effects were not caused by direct drug cytotoxicity.
Ott
Ingo
I
Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria.
Kircher
Brigitte
B
Heinisch
Gottfried
G
Matuszczak
Barbara
B
D002455:Cell Division / Q000187:drug effects; D003989:Dibenzoxazepines / Q000138:chemical synthesis* / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014750:Vincristine / Q000494:pharmacology
D003989:Dibenzoxazepines; D007659:Ketones; D014750:Vincristine