Ebselen, a selenoorganic compound as glutathione peroxidase mimic.
The selenoorganic compound ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, exhibits activity as an enzyme mimic. The reaction catalyzed is that of a glutathione (GSH) peroxidase (i.e., the reduction of a hydroperoxide at the expense of thiol). The specificity for substrates ranges from hydrogen peroxide and smaller organic hydroperoxides to membrane-bound phospholipid and cholesterol hydroperoxides. In addition to glutathione, the thiol reductant cosubstrate can be dithioerythritol, N-acetylcysteine or dihydrolipoate, or other suitable thiol compounds. Ebselen also has properties such as free radical and singlet oxygen quenching. Model experiments in vitro with liposomes, microsomes, isolated cells, and organs show that the protection against oxidative challenge afforded by ebselen can be explained largely by the activity as GSH peroxidase mimic. Whether this also explains the known preliminary results in clinical settings is yet open. The metabolism and disposition of ebselen is presented in this review. The main point is that the selenium is not bioavailable, explaining the extremely low toxicity observed in animal studies. The occurrence of natural GPx mimics, ovothiol and related compounds, is briefly mentioned.
Sies
H
H
Institut für Physiologische Chemie I, Heinrich Heine Universität Düsseldorf, Germany.
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001393:Azoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D054833:Isoindoles; D015227:Lipid Peroxidation / Q000187:drug effects; D016566:Organoselenium Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D010084:Oxidation-Reduction
D000975:Antioxidants; D001393:Azoles; D016166:Free Radical Scavengers; D005609:Free Radicals; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D005979:Glutathione Peroxidase