Syntheses And Evaluation Of Asymmetric Curcumin Analogues As Potential Multifunctional Agents For The Treatment Of Alzheimer's Disease

Curr Alzheimer Res. 2015;12(5):403-14. doi: 10.2174/1567205012666150504151120.

Abstract

A series of new asymmetric curcumin analogues were synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. Our results showed that most of these synthetic compounds had better inhibitory properties against Aβ aggregation compared with curcumin, and better anti-oxidative properties compared with the reference compound Trolox through the study of oxygen radical absorbance capacity (ORAC). Some compounds showed good properties in selectively chelating metal ions such as copper and iron. Besides, some compounds were found to be able to dissociate Aβ protein which had already aggregated. The structure-activity relationships (SAR) of these synthetic compounds were studied. The present investigation indicated that our synthetic asymmetric curcumin derivatives could be potential multifunctional agents for the treatment of Alzheimer's disease (AD).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Amyloid / drug effects
  • Amyloid / metabolism
  • Amyloid beta-Peptides / metabolism
  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology
  • Cell Line, Tumor
  • Chelating Agents / chemical synthesis
  • Chelating Agents / pharmacology
  • Chromans / pharmacology
  • Copper / metabolism
  • Curcumin / analogs & derivatives
  • Curcumin / chemical synthesis*
  • Curcumin / pharmacology*
  • Drug Evaluation
  • Humans
  • Microscopy, Electron, Transmission
  • Molecular Structure
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / pharmacology*
  • Oxygen / chemistry
  • Peptide Fragments / metabolism
  • Protein Aggregates / drug effects
  • Spectrum Analysis
  • Structure-Activity Relationship

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Antioxidants
  • Chelating Agents
  • Chromans
  • Neuroprotective Agents
  • Peptide Fragments
  • Protein Aggregates
  • amyloid beta-protein (1-42)
  • Copper
  • Curcumin
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
  • Oxygen