NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals.

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Bachur NR, Gordon SL, Gee MV, Kon H

NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals.

Proc Natl Acad Sci U S A. 1979 Feb;76(2):954-7.

PubMed ID

34156 [ View in PubMed

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Abstract

With NADPH as the electron donor, rat liver NADPH cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4) catalyzes the single-electron reduction of several quinone antibiotics to a semiquinone or free radical state. The benzanthraquinones adriamycin, daunorubicin, carminomycin, 7-O-methylnogalarol, and aclacinomycin A and the N-heterocyclic quinones streptonigrin and mitomycin C are activated to free radical intermediates which can transfer their single electron to molecular oxygen to form superoxide. The overall Km range for this electron transfer is 0.4 to 42.1 X 10(-4) M. We postulate that the formation of the "site-specific free radical/ intermediate is central to the cytotoxic action of these antibiotics.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Daunorubicin	NADPH--cytochrome P450 reductase	Protein	Humans	Unknown	Substrate Inducer	Details