Towards a modern definition of vitamin E-evidence for a quinone hypothesis

Bioorg Med Chem Lett. 2012 Jan 1;22(1):391-5. doi: 10.1016/j.bmcl.2011.10.117. Epub 2011 Nov 15.

Abstract

We report on the synthesis, biological and pharmacological activity of the tocoquinone natural product, α-tocopherol quinone (ATQ); an oxidative metabolite of α-tocopherol. ATQ is a potent cellular protectant against oxidative stress, whose biological activity is dependent upon its ability to undergo reversible two-electron redox cycling. ATQ is orally bioavailable, with a favorable pharmacokinetic profile and has demonstrated a beneficial clinical response in patients with Friedreich's ataxia. ATQ is a member of a broader class of vitamin E derived quinone metabolites which may be ascribable in whole or in part to the activity of vitamin E.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Design
  • Fibroblasts / metabolism
  • Friedreich Ataxia / metabolism
  • Humans
  • Hydrolases / chemistry
  • Mice
  • Micronucleus Tests
  • Models, Chemical
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Nutritional Sciences*
  • Oxidation-Reduction
  • Oxidative Stress
  • Quinones / chemistry*
  • Rats
  • Vitamin E / analogs & derivatives
  • Vitamin E / chemistry*
  • Vitamin E / metabolism
  • Vitamin E / pharmacology
  • alpha-Tocopherol / metabolism

Substances

  • Quinones
  • Vitamin E
  • tocopherylquinone
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • Hydrolases
  • alpha-Tocopherol