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.
William D Shrader  1 ,  Akiko Amagata ,  Adam Barnes ,  Andrew Hinman ,  Orion Jankowski ,  Edgar Lee ,  Viktoria Kheifets ,  Ryo Komatsuzaki ,  Paul Mollard ,  Katsuyuki Murase ,  Patrice Rioux ,  Kieron Wesson ,  Guy Miller
Affiliations
  • 1. Edison Pharmaceuticals, Inc., 350 North Bernardo Avenue, Mountain View, CA 94043, USA. [email protected]
PMID: 22137789 DOI: 10.1016/j.bmcl.2011.10.117
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.