Design and Synthesis of a Mitochondria-Targeted Mimic of Glutathione Peroxidase, MitoEbselen-2, as a Radiation Mitigator

作者:Stoyanovsky Detcho A*; Jiang Jianfei; Murphy Michael P; Epperly Michael; Zhang Xiaolan; Li Song; Greenberger Joel; Kagan Valerian; Bayir Huelya
来源:ACS Medicinal Chemistry Letters, 2014, 5(12): 1304-1307.
DOI:10.1021/ml5003635

摘要

Ionizing radiation (IR) triggers mitochondrial overproduction of H2O2 and accumulation of lipid hydroperoxides leading to the induction of apoptotic and necroptotic cell death pathways. Given the high catalytic efficiency of the seleno-enzyme glutathione peroxidase (Gpx) toward reduction of lipid hydroperoxides and H2O2, we tested the potential of mitochondria-targeted derivatives of ebselen to mitigate the deleterious effects of IR. We report that 2-[[2-[4-(3-oxo-1,2-benzoselenazol-2-yl)phenyl]acetyl]amino]ethyl-triphenyl-phosphonium chloride (MitoPeroxidase 2) was effective in reducing lipid hydroperoxides, preventing apoptotic cell death, and, when administered 24 h postirradiation, increased the survival of mice exposed to whole body gamma-irradiation.

  • 出版日期2014-12