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

Bioorg Med Chem. 2012 Sep 1;20(17):5188-201. doi: 10.1016/j.bmc.2012.07.005. Epub 2012 Jul 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Cattle
  • Cell Survival / drug effects
  • Cytoprotection / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Lipid Peroxidation / drug effects
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / enzymology
  • Mitochondria, Heart / metabolism
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / metabolism
  • Molecular Structure
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / metabolism
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors
  • NADH, NADPH Oxidoreductases / metabolism
  • Pyridones / chemical synthesis
  • Pyridones / chemistry
  • Pyridones / pharmacology*
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antioxidants
  • Multienzyme Complexes
  • Pyridones
  • Reactive Oxygen Species
  • NADH oxidase
  • NADH, NADPH Oxidoreductases