Nitrones for understanding and ameliorating the oxidative stress associated with aging
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Oxidative damage from reactive oxygen species (ROS) and the carbon-centred radicals arising from them is important to the process of aging, and age-related diseases are generally caused, exacerbated or mediated by oxidative stress. Nitrones can act as spin traps to detect, identify, quantify and locate the radicals responsible using electron paramagnetic resonance (EPR or ESR) spectroscopy, and a new carnitine-derived nitrone, CarnDOD-7C, designed to accumulate in mitochondria is reported. Nitrones also have potential as therapeutic antioxidants, e.g. for slowing cellular aging, and as tools for chemical biology. Two low-molecular weight nitrones, DIPEGN-2 and DIPEGN-3, are reported, which combine high water-solubility with high lipophilicity and obey Lipinski's rule of five.
KeywordsAging Oxidative stress Reactive oxygen species Radicals Electron paramagnetic resonance spectroscopy Nitrones Antioxidants
Scottish Enterprise for Proof of Concept funding. SPARC and the BBSRC for the purchase of the bench-top EPR spectrometer used.
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