Synthesis and anticholinergic activity of 4-hydroxycoumarin derivatives containing substituted benzyl-1,2,3-triazole moiety

Chem Biol Drug Des. 2015 Nov;86(5):1215-20. doi: 10.1111/cbdd.12588. Epub 2015 Jul 20.

Abstract

A series of 4-hydroxycoumarin-derived compounds 8a-p containing N-benzyl-1,2,3-triazole motif were designed as AChE inhibitors. The title compounds were obtained conveniently using multicomponent click reaction. The in vitro anticholinesterase evaluation of synthesized compounds against AChE and BuChE showed that some of them are potent and selective inhibitors of AChE. Among them, 2-chlorobenzyl derivative 8k showed the most potent activity against AChE (IC50 = 0.18 μm). Its activity was also superior to that of standard drug tacrine. The kinetic study and molecular docking simulation of the most potent compound 8k were also described.

Keywords: 1,2,3-Triazole; Alzheimer's disease; acetylcholinesterase; click chemistry; coumarin; docking study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Hydroxycoumarins / chemical synthesis
  • 4-Hydroxycoumarins / chemistry*
  • 4-Hydroxycoumarins / pharmacology*
  • Acetylcholinesterase / metabolism*
  • Animals
  • Cholinergic Antagonists / chemical synthesis
  • Cholinergic Antagonists / chemistry
  • Cholinergic Antagonists / pharmacology
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Click Chemistry
  • Drug Design
  • Electrophorus
  • Kinetics
  • Molecular Docking Simulation
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology*

Substances

  • 4-Hydroxycoumarins
  • Cholinergic Antagonists
  • Cholinesterase Inhibitors
  • Triazoles
  • Acetylcholinesterase
  • 4-hydroxycoumarin