The inhibition of flavoproteins by phenoxaiodonium, a new iodonium analogue

Iodonium compounds, especially diphenylene iodonium and iodonium diphenyl are used extensively as inhibitors of NADH–ubiquinone reductase and NADPH oxidase activity. Here, the use of a new iodonium compound, phenoxaiodonium is reported. The IC 50 of neutrophil superoxide production, measured using t...

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Bibliographic Details
Published in:	European journal of pharmacology Vol. 401; no. 2; pp. 115 - 120
Main Authors:	Moulton, Paul, Martin, Hannah, Ainger, Adele, Cross, Andrew, Hoare, Catherine, Doel, Justin, Harrison, Roger, Eisenthal, Robert, Hancock, John
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 04-08-2000 Elsevier
Subjects:	Analytical, structural and metabolic biochemistry Animals Biological and medical sciences Cattle Dose-Response Relationship, Drug Electron Transport - drug effects Enzyme Inhibitors - pharmacology Enzymes and enzyme inhibitors Flavoproteins - antagonists & inhibitors Fundamental and applied biological sciences. Psychology Iodonium Mitochondria - drug effects Mitochondria - metabolism NADH–ubiquinone reductase NADPH oxidase Neutrophils - drug effects Neutrophils - metabolism Nitric oxidase (NO) synthase Nitric Oxide Synthase - antagonists & inhibitors Nitric Oxide Synthase - metabolism Onium Compounds - chemistry Onium Compounds - pharmacology Oxidoreductases Oxygen - pharmacokinetics Superoxides - metabolism Swine Time Factors Xanthine oxidase Xanthine Oxidase - antagonists & inhibitors Xanthine Oxidase - metabolism Iodonium Xanthine oxidase NADPH oxidase Nitric oxidase (NO) synthase NADH–ubiquinone reductase Enzyme Enzyme inhibitor Superoxide dismutase Flavoprotein In vitro Biological activity Nitric-oxide synthase Free radical Hyperoxides Analog Nitric oxide Iodonium compounds Models Oxidoreductases
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Summary:	Iodonium compounds, especially diphenylene iodonium and iodonium diphenyl are used extensively as inhibitors of NADH–ubiquinone reductase and NADPH oxidase activity. Here, the use of a new iodonium compound, phenoxaiodonium is reported. The IC 50 of neutrophil superoxide production, measured using the superoxide dismutase inhibitable rate of cytochrome c reduction, was approximately 0.75 μM, while 50% inhibition of mitochondrial respiration, measured by the rate of oxygen uptake using a Clark type oxygen electrode, was at approximately 20 μM. The inhibition of oxidation of xanthine to urate by xanthine oxidase was also studied, giving a K i of 0.2 μM. Inhibition of nitric oxidase synthase (NOS: from rat brain) by 0.2 μM phenoxaiodonium was equivalent to 1 mM N G-nitro- l-arginine methyl ester HCl ( l-NAME), that is total abolition of activity. We conclude that phenoxaiodonium is an extremely good inhibitor of flavo-enzymes, but like diphenylene iodonium and iodonium diphenyl, will be of limited use as a pharmacological tool for the elucidation of the involvement of such enzymes in specific cellular functions.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-2999 1879-0712
DOI:	10.1016/S0014-2999(00)00454-4