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

15 Citations (Scopus)

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

Fingerprint

coenzyme Q10
diethyl maleate
Cytoprotection
Electron Transport
Ubiquinone
Mitochondrial Membrane Potential
Chain length
Oxygen Consumption
Glutathione
Cultured Cells
Cells
Oxygen
Derivatives
Membranes
idebenone
Therapeutics

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

Cite this

Fash, D. M., Khdour, O. M., Sahdeo, S. J., Goldschmidt, R., Jaruvangsanti, J., Dey, S., ... 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

Effects of alkyl side chain modification of coenzyme Q10 on mitochondrial respiratory chain function and cytoprotection. / Fash, David M.; Khdour, Omar M.; Sahdeo, Sunil J.; Goldschmidt, Ruth; Jaruvangsanti, Jennifer; Dey, Sriloy; Arce, Pablo M.; Collin, Valérie C.; Cortopassi, Gino A; Hecht, Sidney M.

In: Bioorganic and Medicinal Chemistry, Vol. 21, No. 8, 15.04.2013, p. 2346-2354.

Research output: Contribution to journalArticle

Fash, DM, Khdour, OM, Sahdeo, SJ, Goldschmidt, R, Jaruvangsanti, J, Dey, S, Arce, PM, Collin, VC, Cortopassi, GA & Hecht, SM 2013, 'Effects of alkyl side chain modification of coenzyme Q10 on mitochondrial respiratory chain function and cytoprotection', Bioorganic and Medicinal Chemistry, vol. 21, no. 8, pp. 2346-2354. https://doi.org/10.1016/j.bmc.2013.01.075
Fash, David M. ; Khdour, Omar M. ; Sahdeo, Sunil J. ; Goldschmidt, Ruth ; Jaruvangsanti, Jennifer ; Dey, Sriloy ; Arce, Pablo M. ; Collin, Valérie C. ; Cortopassi, Gino A ; Hecht, Sidney M. / Effects of alkyl side chain modification of coenzyme Q10 on mitochondrial respiratory chain function and cytoprotection. In: Bioorganic and Medicinal Chemistry. 2013 ; Vol. 21, No. 8. pp. 2346-2354.
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