A novel glutathione peroxidase mimic with antioxidant activity

Many diseases are associated with the overproduction of hydroperoxides that inflict cell damage. A novel cyclodextrin derivative, 6A,6B-diseleninic acid-6A',6B'-selenium bridged beta-cyclodextrin (6-diSeCD), was synthesized to be a functional mimic of glutathione peroxidase (GPX) that normally removes these hydroperoxides. The mimic had high catalytic GPX activity of 13.5 U/micromol, which is 13.6-fold higher than ebselen (PZ51), and was chemically and biologically stable in vitro. Antioxidant activity was studied by ferrous sulfate/ascorbate-induced mitochondria damage model system. These data show that the mimic has great antioxidant activity. Such mimics may result in better clinical therapies for diseases mediated by hydroperoxides.