title: Alpha-(phenylselenenyl)acetophenone derivatives with glutathione peroxidase-like activity. A comparison with ebselen.
abstract: Here we describe a new class of organoselenium compounds possessing glutathione peroxidase-like activity. The parent compound, alpha-(phenylselenenyl)acetophenone (PSAP), increased the rate of reaction of glutathione with H2O2, tert-butylhydroperoxide, cumene hydroperoxide, linoleic acid hydroperoxide and dilinoleyl lecithin hydroperoxide by 7.0, 25.1, 34.1, 19.1 and 8.4-fold, respectively, as assessed by the oxidized glutathione (GSSG) reductase enzyme assay. Direct assay of the removal of hydrogen peroxide and glutathione from reaction mixtures confirmed the peroxidase-like activities of these selenoorganic compounds, but indicate that the conventional coupled GSSG reductase assay may be unsuitable for the assessment of the catalytic capacity of PSAP and Ebselen. One possible mechanism of catalysis by PSAP involves an initial oxidation at selenium. Thiol may then react with the selenoxide to yield a selenium (II) compound, H2O and a disulfide. Compounds derived from PSAP may provide potential selenium-based anti-inflammatory agents.
authors.affiliation: Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: I A
authors.initials: IA
authors.lastname: Cotgreave
authors.forename: P
authors.initials: P
authors.lastname: Moldéus
authors.forename: R
authors.initials: R
authors.lastname: Brattsand
authors.forename: A
authors.initials: A
authors.lastname: Hallberg
authors.forename: C M
authors.initials: CM
authors.lastname: Andersson
authors.forename: L
authors.initials: L
authors.lastname: Engman
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis* / Q000378:metabolism; D001393:Azoles / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D054833:Isoindoles; D009249:NADP / Q000378:metabolism; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000098:Acetophenones; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D009249:NADP; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005978:Glutathione