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 the superoxide dismutase inhibitable rate of cytochrome c reduction, was approximately 0.75 microM, while 50% inhibition of mitochondrial respiration, measured by the rate of oxygen uptake using a Clark type oxygen electrode, was at approximately 20 microM. The inhibition of oxidation of xanthine to urate by xanthine oxidase was also studied, giving a K(i) of 0.2 microM. Inhibition of nitric oxidase synthase (NOS: from rat brain) by 0.2 microM 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.
Department of Biological and Biomedical Sciences, University of the West of England, Coldharbour Lane, BS16 1QY, Bristol, UK.
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Moulton
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Martin
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Ainger
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Cross
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Hoare
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Doel
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Harrison
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Eisenthal
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Hancock
D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005420:Flavoproteins / Q000037:antagonists & inhibitors*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009861:Onium Compounds / Q000737:chemistry / Q000494:pharmacology*; D010100:Oxygen / Q000493:pharmacokinetics; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D005420:Flavoproteins; D009861:Onium Compounds; C414204:phenoxaiodonium; D013481:Superoxides; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D010100:Oxygen