Synthesis of some new 3-coumaranone and coumarin derivatives as dual inhibitors of acetyl- and butyrylcholinesterase

Arch Pharm (Weinheim). 2013 Aug;346(8):577-87. doi: 10.1002/ardp.201300080. Epub 2013 Jul 15.

Abstract

A novel series of coumarin and 3-coumaranone derivatives encompassing the phenacyl pyridinium moiety were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity using Ellman's method. All compounds presented inhibitory activity against both AChE and BuChE in the micromolar range. The molecular docking simulations revealed that all compounds were dual binding site inhibitors of AChE. A kinetic study was performed and the mechanism of enzyme inhibition was proved to be of mixed type. All compounds were tested for their antioxidant activity and no significant activity was observed.

Keywords: 3-Coumaranone; Actylcholinesterase; Butyrylcholinesterase; Coumarin; Docking study; Phenacyl pyridinium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism*
  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology
  • Butyrylcholinesterase / chemistry
  • Butyrylcholinesterase / metabolism*
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / pharmacokinetics
  • Cholinesterase Inhibitors / pharmacology*
  • Coumarins / chemical synthesis*
  • Coumarins / pharmacokinetics
  • Coumarins / pharmacology*
  • Drug Design*
  • Kinetics
  • Molecular Docking Simulation
  • Molecular Structure
  • Protein Conformation
  • Structure-Activity Relationship

Substances

  • 3-coumaranone
  • Antioxidants
  • Cholinesterase Inhibitors
  • Coumarins
  • Acetylcholinesterase
  • Butyrylcholinesterase