In vitro evaluation of glutathione peroxidase (GPx)-like activity and antioxidant properties of some Ebselen analogues.
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.
Mouithys-Mickalad Mareque
Ange
A
Centre for Oxygen Research and Development, Institute of Chemistry, University of Liège, Belgium. amouithys@ulg.ac.be
Faez
Juan Mareque
JM
Chistiaens
Léon
L
Kohnen
Stephan
S
Deby
Carol
C
Hoebeke
Maryse
M
Lamy
Maurice
M
Deby-Dupont
Ginette
G
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*
D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D005979:Glutathione Peroxidase