The inhibition of flavoproteins by phenoxaiodonium, a new iodonium analogue

• Published in: European journal of pharmacology 2000-08, Vol.401 (2), p.115-120
• Main Authors: Moulton, Paul, Martin, Hannah, Ainger, Adele, Cross, Andrew, Hoare, Catherine, Doel, Justin, Harrison, Roger, Eisenthal, Robert, Hancock, John
• Format: Article
• Language: English
• 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
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00454-4

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.