Design, Synthesis, Biological Evaluation, and Docking Study of Acetylcholinesterase Inhibitors: New Acridone-1,2,4-oxadiazole-1,2,3-triazole Hybrids

Chem Biol Drug Des. 2015 Dec;86(6):1425-32. doi: 10.1111/cbdd.12609. Epub 2015 Jul 20.

Abstract

In this study, novel acridone-1,2,4-oxadiazole-1,2,3-triazole hybrids were designed, synthesized, and evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activity. Among various synthesized compounds, 10-((1-((3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)acridin-9(10H)-one 10b showed the most potent anti-acetylcholinesterase activity (IC50 = 11.55 μm) being as potent as rivastigmine. Also docking outcomes were in good agreement with in vitro results confirming the dual binding inhibitory activity of compound 10b.

Keywords: Alzheimer's disease; acetylcholinesterase; acridone-1,2,4-oxadiazole-1,2,3-triazole; docking study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acridones / chemical synthesis*
  • Acridones / chemistry
  • Acridones / pharmacology*
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Catalytic Domain
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Drug Design
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Humans
  • Hydrogen Bonding
  • Molecular Docking Simulation
  • Structure-Activity Relationship

Substances

  • Acridones
  • Antioxidants
  • Cholinesterase Inhibitors
  • Free Radical Scavengers
  • Acetylcholinesterase