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

Bioorg Med Chem. 2013 Apr 15;21(8):2346-2354. doi: 10.1016/j.bmc.2013.01.075. Epub 2013 Feb 13.


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.

MeSH terms

  • Animals
  • Cattle
  • Cell Line
  • Cell Line, Tumor
  • Cytoprotection
  • Electron Transport / drug effects*
  • Electron Transport / physiology
  • Humans
  • Leukemia / metabolism
  • Leukemia / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxygen Consumption / drug effects
  • Reactive Oxygen Species / metabolism
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Structure-Activity Relationship
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / chemistry
  • Ubiquinone / metabolism
  • Ubiquinone / pharmacology


  • Reactive Oxygen Species
  • Ubiquinone
  • coenzyme Q10