Simplified bicyclic pyridinol analogues protect mitochondrial function

Xiaoqing Cai, Omar Khdour, Jennifer Jaruvangsanti, Sidney Hecht

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Bicyclic pyridinol antioxidants have been reported to suppress the autoxidation of methyl linoleate more effectively than α-tocopherol in benzene solution. A few novel lipophilic analogues have recently been synthesized by conjugating a pyridinol core with the phytyl side chain of α-tocopherol; these have been shown to possess potent antioxidant activity. However, the complexity of the synthetic routes has hampered their further development. Herein, we describe a facile approach, involving only five synthetic steps, to simplified analogues (1a-1c) and their acetate ester precursors (2a-2c). Simple alkyl chains of different lengths were attached to the 6-methyl group of the antioxidant core via regioselective metalation. These analogues were found to retain biological activity and exhibit protective behaviour under conditions of induced oxidative stress, which could lead to the development of more readily accessible analogues as potential antioxidants capable of preserving mitochondrial function.

Original languageEnglish (US)
Pages (from-to)3584-3595
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number11
DOIs
StatePublished - Jun 1 2012

Fingerprint

Antioxidants
Tocopherols
Oxidative stress
Bioactivity
Benzene
Esters
Acetates
Oxidative Stress

Keywords

  • Bicyclic pyridinol antioxidant
  • Lipid peroxidation
  • Mitochondrial dysfunction
  • Mitochondrial membrane potential
  • Reactive oxygen species

ASJC Scopus subject areas

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

Cite this

Simplified bicyclic pyridinol analogues protect mitochondrial function. / Cai, Xiaoqing; Khdour, Omar; Jaruvangsanti, Jennifer; Hecht, Sidney.

In: Bioorganic and Medicinal Chemistry, Vol. 20, No. 11, 01.06.2012, p. 3584-3595.

Research output: Contribution to journalArticle

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