Synthesis and characterization of mitoQ and idebenone analogues as mediators of oxygen consumption in mitochondria

Bioorg Med Chem. 2010 Sep 1;18(17):6429-41. doi: 10.1016/j.bmc.2010.06.104. Epub 2010 Aug 4.

Abstract

Analogues of mitoQ and idebenone were synthesized to define the structural elements that support oxygen consumption in the mitochondrial respiratory chain. Eight analogues were prepared and fully characterized, then evaluated for their ability to support oxygen consumption in the mitochondrial respiratory chain. While oxygen consumption was strongly inhibited by mitoQ analogues 2-4 in a chain length-dependent manner, modification of idebenone by replacement of the quinone methoxy groups by methyl groups (analogues 6-8) reduced, but did not eliminate, oxygen consumption. Idebenone analogues 6-8 also displayed significant cytoprotective properties toward cultured mammalian cells in which glutathione had been depleted by treatment with diethyl maleate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology
  • Cytoprotection
  • Glutathione / metabolism
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Organophosphorus Compounds / chemical synthesis*
  • Organophosphorus Compounds / pharmacology*
  • Oxygen Consumption / drug effects*
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / chemical synthesis
  • Ubiquinone / pharmacology

Substances

  • 10-(6'-ubiquinonyl)decyltriphenylphosphonium bromide
  • Antioxidants
  • Organophosphorus Compounds
  • Ubiquinone
  • Glutathione
  • idebenone