Effects of alkyl side chain modification of coenzyme Q10 on mitochondrial respiratory chain function and cytoprotection

David M. Fash, Omar M. Khdour, Sunil J. Sahdeo, Ruth Goldschmidt, Jennifer Jaruvangsanti, Sriloy Dey, Pablo M. Arce, Valérie C. Collin, Gino A Cortopassi, Sidney M. Hecht

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The effect of the alkyl side chain length of coenzyme Q10 on mitochondrial respiratory chain function has been investigated by the use of synthetic ubiquinone derivatives. Three analogues (3, 4 and 6) were identified that exhibited significantly improved effects on mitochondrial oxygen consumption and mitochondrial membrane potential, and also conferred significant cytoprotection on cultured mammalian cells in which glutathione had been depleted by treatment with diethyl maleate. The analogues also exhibited lesser inhibition of the electron transport chain than idebenone. The results obtained provide guidance for the design of CoQ10 analogues with improved activity compared to that of idebenone (1), the latter of which is undergoing evaluation in the clinic as a therapeutic agent.

Original languageEnglish (US)
Pages (from-to)2346-2354
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number8
DOIs
StatePublished - Apr 15 2013

Keywords

  • Coenzyme Q
  • Cytoprotection
  • Electron transport chain
  • Oxygen consumption
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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    Fash, D. M., Khdour, O. M., Sahdeo, S. J., Goldschmidt, R., Jaruvangsanti, J., Dey, S., Arce, P. M., Collin, V. C., Cortopassi, G. A., & Hecht, S. M. (2013). Effects of alkyl side chain modification of coenzyme Q10 on mitochondrial respiratory chain function and cytoprotection. Bioorganic and Medicinal Chemistry, 21(8), 2346-2354. https://doi.org/10.1016/j.bmc.2013.01.075