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

Damien Y. Duveau, Pablo M. Arce, Robert A. Schoenfeld, Nidhi Raghav, Gino A. Cortopassi, Sidney Hecht

Research output: Contribution to journalArticle

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6429-6441
Number of pages13
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number17
DOIs
StatePublished - Sep 1 2010

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Keywords

  • Cytoprotection
  • Idebenone
  • Mitochondrial respiration
  • Oxygen consumption
  • Ubiquinones

ASJC Scopus subject areas

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

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