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.
Moulton
P
P
Department of Biological and Biomedical Sciences, University of the West of England, Coldharbour Lane, BS16 1QY, Bristol, UK.
Martin
H
H
Ainger
A
A
Cross
A
A
Hoare
C
C
Doel
J
J
Harrison
R
R
Eisenthal
R
R
Hancock
J
J
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