title: In vitro evaluation of glutathione peroxidase (GPx)-like activity and antioxidant properties of some Ebselen analogues.
abstract: Four analogues of Ebselen were synthesized and their glutathione peroxidase activity and antioxidant property evaluated and compared to Ebselen. Among the studied compounds, only diselenide [3] exhibited both glutathione peroxidase activity and radical-scavenging capability. Compounds [3] and [4] showed a strong inhibitory effect (53% and 43%, respectively) on the lipid peroxidation of linoleic acid compared to Ebselen and selenide derivatives ([1] and [2]) which were less active (28%, 26% and 18% inhibition, respectively). A concentration-dependent inhibitory effect was also found in the model of the formation of ABTS*+ radical cation: 65% and 89% inhibition for compound [3] at 10(-4) M and 5 x 10(-5) M, respectively, and 68% and 90% for compound [4], compared to 14% and 52% inhibition for Ebselen and the diselenides [1] and [2] (29%, 46% and 45%, 68%, respectively). By EPR spin trapping technique, the following inhibitory profile of the Ebselen analogues was observed towards the formation of thiyl radicals: Ebselen = [3]>[1]>[2]>[4]. Studies with compound [3] are in progress on oxidative stress cell models.
authors.affiliation: Centre for Oxygen Research and Development, Institute of Chemistry, University of Liège, Belgium. amouithys@ulg.ac.be
authors.forename: Ange
authors.initials: A
authors.lastname: Mouithys-Mickalad Mareque
authors.forename: Juan Mareque
authors.initials: JM
authors.lastname: Faez
authors.forename: Léon
authors.initials: L
authors.lastname: Chistiaens
authors.forename: Stephan
authors.initials: S
authors.lastname: Kohnen
authors.forename: Carol
authors.initials: C
authors.lastname: Deby
authors.forename: Maryse
authors.initials: M
authors.lastname: Hoebeke
authors.forename: Maurice
authors.initials: M
authors.lastname: Lamy
authors.forename: Ginette
authors.initials: G
authors.lastname: Deby-Dupont
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D001393:Azoles / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005979:Glutathione Peroxidase / Q000378:metabolism*; D066298:In Vitro Techniques; D054833:Isoindoles; D015227:Lipid Peroxidation; D016566:Organoselenium Compounds / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D005979:Glutathione Peroxidase