NO and HNO donors, nitrones, and nitroxides: Past, present, and future

The biological effects attributed to nitric oxide ((NO)-N-center dot) and nitroxyl (HNO) have been extensively studied, propelling their array of putative clinical applications beyond cardiovascular disorders toward other age-related diseases, like cancer and neurodegenerative diseases. In this context, the unique properties and reactivity of the N-O bond enabled the development of several classes of compounds with potential clinical interest, among which (NO)-N-center dot and HNO donors, nitrones, and nitroxides are of particular importance. Although primarily studied for their application as cardioprotective agents and/or molecular probes for radical detection, continuous efforts have unveiled a wide range of pharmacological activities and, ultimately, therapeutic applications. These efforts are of particular significance for diseases in which oxidative stress plays a key pathogenic role, as shown by a growing volume of in vitro and in vivo preclinical data. Although in its early stages, these efforts may provide valuable guidelines for the development of new and effective N-O-based drugs for age-related disorders. In this report, we review recent advances in the chemistry of NO and HNO donors, nitrones, and nitroxides and discuss its pharmacological significance and potential therapeutic application.