Design, synthesis and glutathione peroxidase-like properties of ovothiol-derived diselenides

Eleven imidazole diselenides derived from the naturally occurring family of antioxidants, the ovothiols, were synthetised by cyclisation of selenoamides with trimethylsilyltrifluoromethanesulfonate or refluxing of cyanoamines in a selenium/sodium borohydride mixture. These compounds were assayed for their glutathione peroxidase-like (GSH Px-like) activity and their capacity to be reduced by glutathione. The most active molecules of the series were 4 times more potent in the GSH Px-like test than the widely known reference compound, ebselen. This catalytic activity was mediated by the formation of the antioxidant selenol intermediate upon partial but significant exchange reaction with glutathione.