Microsomal metabolism of quinifuryl--a nitrofuryl-ethenyl-quinolone antiseptic possessing antitumor activity in vitro.
Quinifuryl, 2-(5'-nitro-2'-furanyl)ethenyl-4-[N-[4'-(N,N-diethylamino)-1'-methylbuty l] carbamoyl] quinoline, is a representative of a family of nitrofuran-ethenyl-quinoline antibiotics synthesized in the USSR by Dr N.M. Sukhova. The drug has been shown to be an effective cytostatic and radiosensitizer towards cancer cells in culture. While rapid metabolic consumption of these drugs by liver tissue has been shown, none of the drug metabolites have been isolated and characterized. Here, we present the results of experiments focusing on the isolation and characterization of quinifuryl metabolites. A pyridine derivative was the sole product detected and characterized by GC-MS analysis. An alteration of quinifuryl metabolism by peroxynitrite formed during the metabolism of the drug was assumed to be responsible for an unexpectedly high drug decomposition.
Degterev
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IA
Departamento de Patologia Clínica, Faculdade de Ciências Médicas, UNICAMP, Campinas, SP, Brasil.
Nogueira
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PC
Marsaioli
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AJ
Verces
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AE
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism; D004347:Drug Interactions; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D009566:Nitrates / Q000494:pharmacology*; D016877:Oxidants / Q000737:chemistry; D011725:Pyridines / Q000032:analysis*; D011804:Quinolines / Q000378:metabolism*
D000891:Anti-Infective Agents, Local; D000970:Antineoplastic Agents; D009566:Nitrates; D016877:Oxidants; D011725:Pyridines; D011804:Quinolines; C099760:quinifuryl; C039642:peroxynitric acid