Design, synthesis, and biological evaluation of curcumin analogues as multifunctional agents for the treatment of Alzheimer's disease

Bioorg Med Chem. 2011 Sep 15;19(18):5596-604. doi: 10.1016/j.bmc.2011.07.033. Epub 2011 Jul 24.

Abstract

A series of novel curcumin analogues were designed, synthesized, and evaluated as potential multifunctional agents for the treatment of AD. The in vitro studies showed that these compounds had better inhibitory properties against Aβ aggregation than curcumin. Superior anti-oxidant properties (better than the reference compound Trolox) of these compounds were observed by the oxygen radical absorbance capacity (ORAC) method and a cell-based assay using DCFH-DA as a probe. In addition they were able to chelate metals such as iron and copper and decrease metal-induced Aβ aggregation. The structure-activity relationships were discussed. The results suggested that our curcumin analogues could be selected as multifunctional agents for further investigation of AD treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Antioxidants / metabolism
  • Cell Line, Tumor
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacology
  • Curcumin / analogs & derivatives
  • Curcumin / chemical synthesis*
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Molecular Structure
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / metabolism
  • Reactive Oxygen Species / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Chelating Agents
  • Peptide Fragments
  • Reactive Oxygen Species
  • amyloid beta-protein (1-42)
  • Curcumin