Design, synthesis, biological evaluation and docking study of 5-oxo-4,5-dihydropyrano[3,2-c]chromene derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors

Eur J Med Chem. 2013 Oct:68:260-9. doi: 10.1016/j.ejmech.2013.07.038. Epub 2013 Aug 11.

Abstract

A series of fused coumarins namely 5-oxo-4,5-dihydropyrano[3,2-c]chromenes linked to N-benzylpyridinium scaffold were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The 1-(4-fluorobenzyl)pyridinium derivative 6g showed the most potent anti-AChE activity (IC50 value=0.038 μM) and the highest AChE/BuChE selectivity (SI>48). The docking study permitted us to rationalize the observed structure-affinity relationships and to detect possible binding modes.

Keywords: Acetylcholinesterase; Alzheimer's disease; Chromenes; Coumarins; Docking study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / chemistry
  • Benzopyrans / pharmacology*
  • Binding Sites
  • Butyrylcholinesterase / metabolism*
  • Catalytic Domain
  • Cholinesterase Inhibitors* / chemical synthesis
  • Cholinesterase Inhibitors* / pharmacology
  • Drug Design*
  • Enzyme Activation / drug effects
  • Models, Biological
  • Models, Molecular
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Benzopyrans
  • Cholinesterase Inhibitors
  • Acetylcholinesterase
  • Butyrylcholinesterase