Analysis of the structural and mechanistic factors in antioxidants that preserve mitochondrial function and confer cytoprotection

Pablo M. Arce, Ruth Goldschmidt, Omar Khdour, Manikandadas M. Madathil, Jennifer Jaruvangsanti, Sriloy Dey, David M. Fash, Jeffrey S. Armstrong, Sidney Hecht

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Selected pyridinol analogues of the experimental neuroprotective drug idebenone have been synthesized and evaluated as antioxidants capable of preserving mitochondrial function. The compounds, having a different redox core but the same side chain as idebenone, exhibited a range of potencies, reflecting differences in their structures. The results obtained provide guidance in the design of such analogues with improved properties. Analogues were identified that have significantly improved antioxidant activity compared with idebenone in cultured lymphocytes, and which exhibit lesser inhibition of the electron transport chain.

Original languageEnglish (US)
Pages (from-to)5188-5201
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number17
DOIs
StatePublished - Sep 1 2012

Keywords

  • Electron transport chain
  • Idebenone
  • Mitochondrial dysfunction
  • Reactive oxygen species

ASJC Scopus subject areas

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

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