Synthesis of novel chromenones linked to 1,2,3-triazole ring system: Investigation of biological activities against Alzheimer's disease

Bioorg Chem. 2017 Feb:70:86-93. doi: 10.1016/j.bioorg.2016.11.011. Epub 2016 Nov 24.

Abstract

In this work, novel chromenones linked to 1,2,3-triazole ring system were synthesized and evaluated for their anti-ChE activity. Among them, N-((1-(2-chlorobenzyl)-1H-1,2,3-triazol-5-yl)methyl)-8-methoxy-2-oxo-2H-chromene-3-carboxamide (6m) showed good anti-acetylcholinesterase activity (IC50=15.42μM). Also, compound 6m demonstrated neuroprotective effect against H2O2-induced cell death in PC12 neurons, however, it showed no beta-secretase (BACE1) inhibitory activity. Docking and kinetic studies separately confirmed dual binding activity of compound 6m since it targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE.

Keywords: 1,2,3-Triazole; Alzheimer’s disease; Anti-cholinesterase; Chromenones; Docking study; Neuroprotective activity; β-Secretase inhibitory activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / enzymology
  • Animals
  • Benzopyrans / chemistry*
  • Benzopyrans / pharmacology*
  • Cell Death / drug effects
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • PC12 Cells
  • Rats
  • Triazoles / chemistry*
  • Triazoles / pharmacology*

Substances

  • Benzopyrans
  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Triazoles
  • Acetylcholinesterase