Alpha-(phenylselenenyl)acetophenone derivatives with glutathione peroxidase-like activity. A comparison with ebselen

Biochem Pharmacol. 1992 Feb 18;43(4):793-802. doi: 10.1016/0006-2952(92)90245-e.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / chemical synthesis*
  • Acetophenones / metabolism
  • Azoles / metabolism*
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism*
  • Hydrogen Peroxide / metabolism
  • Isoindoles
  • NADP / metabolism
  • Organoselenium Compounds / chemical synthesis*
  • Organoselenium Compounds / metabolism*
  • Structure-Activity Relationship

Substances

  • Acetophenones
  • Azoles
  • Isoindoles
  • Organoselenium Compounds
  • ebselen
  • NADP
  • Hydrogen Peroxide
  • Glutathione Peroxidase
  • Glutathione