Novel racemic tetrahydrocurcuminoid dihydropyrimidinone analogues as potent acetylcholinesterase inhibitors

Bioorg Med Chem Lett. 2013 May 15;23(10):2880-2. doi: 10.1016/j.bmcl.2013.03.069. Epub 2013 Apr 1.

Abstract

The synthesis of racemic tetrahydrocurcumin- (THC-), tetrahydrodemethoxycurcumin- (THDC-) and tetrahydrobisdemethoxycurcumin- (THBDC-) dihydropyrimidinone (DHPM) analogues was achieved by utilizing the multi-component Biginelli reaction in the presence of copper sulphate as a catalyst. The evaluation of acetylcholinesterase inhibitors for Alzheimer's disease of these compounds showed that they exhibited higher inhibitory activity than their parent analogues. THBDC-DHPM demonstrated the most potent inhibitory activity with an IC50 value of 1.34±0.03μM which was more active than the approved drug galanthamine (IC50=1.45±0.04μM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Curcumin / analogs & derivatives*
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Pyrimidines
  • Acetylcholinesterase
  • Curcumin