Synthesis and Evaluation of Chroman-4-One Linked to N-Benzyl Pyridinium Derivatives as New Acetylcholinesterase Inhibitors

Arch Pharm (Weinheim). 2015 Sep;348(9):643-9. doi: 10.1002/ardp.201500149. Epub 2015 Jul 20.

Abstract

A novel series of chroman-4-one derivatives containing the N-benzyl pyridinium moiety were designed, synthesized, and evaluated for their acetylcholinesterase (AChE) inhibitory activities. Among the various synthesized compounds, (E)-1-(2,3-dibromobenzyl)-4-((7-ethoxy-4-oxochroman-3-ylidene)methyl)pyridinium bromide (8l) depicted the most potent anti-AChE activity (IC50 = 0.048 μM). In addition, the molecular modeling study allowed us to detect possible binding modes that are in full compliance with the observed results through in vitro experiments.

Keywords: Acetylcholinesterase; Alzheimer's disease; Chroman-4-one; Docking study; N-Benzyl pyridinium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism*
  • Benzyl Compounds / chemical synthesis*
  • Benzyl Compounds / pharmacology*
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / pharmacology*
  • Drug Design
  • Molecular Docking Simulation
  • Protein Conformation
  • Pyridinium Compounds / chemical synthesis*
  • Pyridinium Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • Benzyl Compounds
  • Cholinesterase Inhibitors
  • Pyridinium Compounds
  • Acetylcholinesterase