Diagnostic and therapeutic applications of azulenyl nitrone spin traps

Abstract.

Azulenyl nitrones have been recently demonstrated to constitute a new class of nitrone-based spin traps with the unprecedented capacity to tag free radicals by yielding characteristically colored and highly visible diamagnetic (and paramagnetic) spin adducts. In addition, a comparison of the oxidation potentials of azulenyl nitrones such as 1 and congeners to those of conventional nitrone spin traps previously investigated as potential antioxidant therapeutics such as N-tert-butyl-α-phenylnitrone and its related ortho-sodium sulfonate reveals that the azulene-derived spin traps are far more readily oxidized. These special features render azulenyl nitrones of interest with regard to both their distinct ability to engender the convenient use of colorimetric detection to monitor free radical-mediated oxidative stress in biological systems, and to their potentially enhanced efficacy as neuroprotective antioxidants vs. those conventional nitrone spin traps earlier examined as such. Herein is reported an overview of recent developments pertaining to the use of azulenyl nitrones in the detection of oxidative stress in animal models of amyotrophic lateral sclerosis and stroke, and to their neuroprotective activity in animal models of Parkinson’s disease, stroke and neurodegeneration within the retina.