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

26 Citations (Scopus)

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

Fingerprint

Mitochondria
Oxygen Consumption
Oxygen
diethyl maleate
Electron Transport
Chain length
Glutathione
Cultured Cells
Cells
idebenone

Keywords

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

ASJC Scopus subject areas

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

Cite this

Synthesis and characterization of mitoQ and idebenone analogues as mediators of oxygen consumption in mitochondria. / Duveau, Damien Y.; Arce, Pablo M.; Schoenfeld, Robert A.; Raghav, Nidhi; Cortopassi, Gino A.; Hecht, Sidney.

In: Bioorganic and Medicinal Chemistry, Vol. 18, No. 17, 01.09.2010, p. 6429-6441.

Research output: Contribution to journalArticle

Duveau, Damien Y. ; Arce, Pablo M. ; Schoenfeld, Robert A. ; Raghav, Nidhi ; Cortopassi, Gino A. ; Hecht, Sidney. / Synthesis and characterization of mitoQ and idebenone analogues as mediators of oxygen consumption in mitochondria. In: Bioorganic and Medicinal Chemistry. 2010 ; Vol. 18, No. 17. pp. 6429-6441.
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