Towards a modern definition of vitamin E-evidence for a quinone hypothesis |
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Authors: | Shrader William D Amagata Akiko Barnes Adam Hinman Andrew Jankowski Orion Lee Edgar Kheifets Viktoria Komatsuzaki Ryo Mollard Paul Murase Katsuyuki Rioux Patrice Wesson Kieron Miller Guy |
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Institution: | Edison Pharmaceuticals, Inc., 350 North Bernardo Avenue, Mountain View, CA 94043, USA. bshrader@edisonpharma.com |
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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. |
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