Nitrone therapeutics has been employed in the treatment of oxidative 
stress-related diseases such as neurodegeneration, cardiovascular disease and 
cancer. The nitrone-based compound NXY-059, which is the first drug to reach 
clinical trials for the treatment of acute ischemic stroke, has provided promise 
for the development of more robust pharmacological agents. However, the specific 
mechanism of nitrone bioactivity remains unclear. In this review, we present a 
variety of nitrone chemistry and biological activity that could be implicated 
for the nitrone's pharmacological activity. The chemistries of spin trapping and 
spin adduct reveal insights on the possible roles of nitrones for altering 
cellular redox status through radical scavenging or nitric oxide donation, and 
their biological effects are presented. An interdisciplinary approach towards 
the development of novel synthetic antioxidants with improved pharmacological 
properties encompassing theoretical, synthetic, biochemical and in vitro/in vivo 
studies is covered.