Nitroxides as Antioxidants and Anticancer Drugs

Int J Mol Sci. 2017 Nov 22;18(11):2490. doi: 10.3390/ijms18112490.

Abstract

Nitroxides are stable free radicals that contain a nitroxyl group with an unpaired electron. In this paper, we present the properties and application of nitroxides as antioxidants and anticancer drugs. The mostly used nitroxides in biology and medicine are a group of heterocyclic nitroxide derivatives of piperidine, pyrroline and pyrrolidine. The antioxidant action of nitroxides is associated with their redox cycle. Nitroxides, unlike other antioxidants, are characterized by a catalytic mechanism of action associated with a single electron oxidation and reduction reaction. In biological conditions, they mimic superoxide dismutase (SOD), modulate hemoprotein's catalase-like activity, scavenge reactive free radicals, inhibit the Fenton and Haber-Weiss reactions and suppress the oxidation of biological materials (peptides, proteins, lipids, etc.). The use of nitroxides as antioxidants against oxidative stress induced by anticancer drugs has also been investigated. The application of nitroxides and their derivatives as anticancer drugs is discussed in the contexts of breast, hepatic, lung, ovarian, lymphatic and thyroid cancers under in vivo and in vitro experiments. In this article, we focus on new natural spin-labelled derivatives such as camptothecin, rotenone, combretastatin, podophyllotoxin and others. The applications of nitroxides in the aging process, cardiovascular disease and pathological conditions were also discussed.

Keywords: antioxidant properties; nitroxide; nitroxide as drugs; oxidative stress; spin labelled drug analogues.

Publication types

  • Review

MeSH terms

  • Aging / metabolism
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Disease Susceptibility
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Nitrogen Oxides / chemistry
  • Nitrogen Oxides / pharmacology*
  • Nitrogen Oxides / therapeutic use
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Superoxide Dismutase / metabolism

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Nitrogen Oxides
  • Doxorubicin
  • Superoxide Dismutase
  • nitroxyl