Antioxidant properties of nitecapone (OR-462).
Nitecapone [3-(3,4-dihydroxy-5-nitrophenyl)methylene-2,4-pentanedione] [OR-462] is a catechol-O-methyltransferase inhibitor with gastroprotective properties. Recently, its antioxidant properties have been discovered: It scavenges peroxyl radicals (ROO.) and thus spares glutathione. Further examination of the properties of nitecapone demonstrated a remarkable ability of this compound to act as an antioxidant: (1) to scavenge ROO. in solution with a stoichiometry factor of 2; (2) to scavenge ROO. in membranes; (3) to inhibit lipid peroxidation; (4) to act as a competitive inhibitor for xanthine oxidase with Ki of 8.8 microM; (5) to scavenge O2- with a second order kinetic rate constant of 1.0 x 10(4) M-1 s-1; and (6) to scavenge HO.. Nitecapone also interacts with oxidation product of ascorbate to participate in recycling of vitamin E. Thus, nitecapone potentially is an effective therapeutic antioxidant, and the use of this compound in a combination with other antioxidants may be beneficial.
Suzuki
Y J
YJ
Department of Molecular & Cell Biology, University of California, Berkeley 94720.
Tsuchiya
M
M
Safadi
A
A
Kagan
V E
VE
Packer
L
L
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid; D001391:Azo Compounds / Q000494:pharmacology; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008163:Luminescent Measurements; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D008892:Milk / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010422:Pentanones / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013481:Superoxides / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D001391:Azo Compounds; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D009570:Nitriles; D010422:Pentanones; D017392:Thiobarbituric Acid Reactive Substances; C055792:2,2'-azobis(2,4-dimethylvaleronitrile); D013481:Superoxides; C057364:nitecapone; D014969:Xanthine Oxidase; D001205:Ascorbic Acid