Design, synthesis and evaluation of flavonoid derivatives as potent AChE inhibitors

Bioorg Med Chem. 2009 Sep 15;17(18):6692-8. doi: 10.1016/j.bmc.2009.07.072. Epub 2009 Aug 3.

Abstract

A new series of flavonoid derivatives have been designed, synthesized and evaluated as potent AChE inhibitors. Most of them showed more potent inhibitory activities to AChE than rivastigmine. The most potent inhibitor isoflavone derivative 10d inhibit AChE with a IC(50) of 4 nM and showed high BChE/AChE inhibition ratio (4575-fold), superior to donepezil (IC(50)=12 nM, 389-fold). Molecular docking studies were also performed to explore the detailed interaction with AChE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism*
  • Animals
  • Binding Sites
  • Butyrylcholinesterase / chemistry
  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Computer Simulation
  • Flavonoids / chemical synthesis
  • Flavonoids / chemistry*
  • Flavonoids / pharmacology*
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Structure
  • Phenylcarbamates / pharmacology
  • Protein Binding
  • Rats
  • Rivastigmine
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Flavonoids
  • Phenylcarbamates
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Rivastigmine