Effects of cytoprotective antioxidants on lymphocytes from representative mitochondrial neurodegenerative diseases

Ruth Goldschmidt, Pablo M. Arce, Omar Khdour, Valérie C. Collin, Sriloy Dey, Jennifer Jaruvangsanti, David M. Fash, Sidney Hecht

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Two new aza analogues of the neuroprotective agent idebenone have been synthesized and characterized. Their antioxidant activity, and ability to augment ATP levels have been evaluated in several different cell lines having suboptimal mitochondrial function. Both compounds were found to be good ROS scavengers, and to protect the cells from oxidative stress induced by glutathione depletion. The compounds were more effective than idebenone in neurodegenerative disease cells. These novel pyrimidinol derivatives were also shown to augment ATP levels in coenzyme Q10-deficient human lymphocytes. The more lipophilic side chains attached to the pyrimidinol redox core in these compounds resulted in less inhibition of the electron transport chain and improved antioxidant activity.

Original languageEnglish (US)
Pages (from-to)969-978
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number4
DOIs
StatePublished - Feb 15 2013

Keywords

  • Adenosine triphosphate
  • Antioxidants
  • Electron transport chain
  • 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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