Toward a rational design of multitarget-directed antioxidants: merging memoquin and lipoic acid molecular frameworks

J Med Chem. 2009 Dec 10;52(23):7883-6. doi: 10.1021/jm901123n.

Abstract

Novel multitargeted antioxidants 3-6 were designed by combining the antioxidant features, namely, a benzoquinone fragment and a lipoyl function, of two multifunctional lead candidates. They were then evaluated to determine their profile against Alzheimer's disease. They showed antioxidant activity, improved following enzymatic reduction, in mitochondria and T67 cell line. They also displayed a balanced inhibitory profile against amyloid-beta aggregation and acetylcholinesterase, emerging as promising molecules for neuroprotectant lead discovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanes / chemistry*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / prevention & control
  • Alzheimer Disease / therapy
  • Amyloid beta-Peptides / metabolism
  • Antioxidants / chemistry*
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Cell Line, Tumor
  • Drug Design
  • Electron Transport
  • Ethylamines / chemistry*
  • Humans
  • Ligands
  • Protein Binding / drug effects
  • Reactive Oxygen Species / metabolism
  • Submitochondrial Particles / drug effects
  • Submitochondrial Particles / metabolism
  • Thioctic Acid / chemistry*
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / metabolism

Substances

  • Alkanes
  • Amyloid beta-Peptides
  • Antioxidants
  • Ethylamines
  • Ligands
  • Reactive Oxygen Species
  • memoquin
  • Ubiquinone
  • Thioctic Acid
  • ubiquinol