The reaction of ebselen with peroxynitrite.
Ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, rapidly reacts with peroxynitrite, the rate constant being of the order of 10(6) M-1 s-1; the reaction yields the selenoxide of the parent molecule, 2-phenyl-1,2-benzisoselenazol-3(2H)-one 1-oxide, as the sole selenium-containing product; a stoichiometry of 1 mol of ebselen reacted and of the selenoxide formed per mole of peroxynitrite was observed. The reaction was studied in detail at neutral and alkaline pH (pH 10-11). It also proceeds at acidic pH where peroxynitrous acid (ONOOH) is predominant, the yield of the selenoxide being lower because peroxynitrous acid (pKa = 6.8) decays rapidly. Reduction of the selenoxide in cells to regenerate ebselen would allow for a sustained defense against peroxynitrite. This novel reaction constitutes a potential cellular defense line against peroxynitrite, one of the important reactive species in inflammatory processes.
Masumoto
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Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
Sies
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D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001393:Azoles / Q000737:chemistry* / Q000494:pharmacology*; D004347:Drug Interactions; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D054833:Isoindoles; D009566:Nitrates / Q000737:chemistry* / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000494:pharmacology*; D018036:Selenium Compounds / Q000737:chemistry; D064588:Selenium Oxides; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D009566:Nitrates; D009573:Nitrites; D016566:Organoselenium Compounds; D018036:Selenium Compounds; D064588:Selenium Oxides; C039642:peroxynitric acid; C042986:ebselen