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

Med Res Rev. 2018 Jul;38(4):1159-1187. doi: 10.1002/med.21461. Epub 2017 Nov 2.

Abstract

The biological effects attributed to nitric oxide ( NO) 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 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.

Keywords: age-related diseases; nitric oxide donors; nitrones; nitroxides; nitroxyl donors; spin traps.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / therapeutic use
  • Cardiovascular Diseases / drug therapy*
  • Drug Design
  • Drug Discovery / history
  • Drug Discovery / trends
  • History, 21st Century
  • Humans
  • Mice
  • Neoplasms / drug therapy*
  • Neurodegenerative Diseases / drug therapy*
  • Nitric Oxide / chemistry*
  • Nitrogen Oxides / chemistry*
  • RAW 264.7 Cells
  • Spin Trapping
  • Vasodilator Agents / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Nitrogen Oxides
  • Vasodilator Agents
  • nitrones
  • Nitric Oxide
  • nitroxyl