Design, synthesis, docking study and biological evaluation of some novel tetrahydrochromeno [3',4':5,6]pyrano[2,3-b]quinolin-6(7H)-one derivatives against acetyl- and butyrylcholinesterase

Eur J Med Chem. 2013 Oct:68:291-300. doi: 10.1016/j.ejmech.2013.07.045. Epub 2013 Aug 11.


Novel hybrid derivatives of two known scaffolds; tetrahydroaminoquinoline and coumarin were synthesized and evaluated for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. By means of an efficient nanocatalyst, the reaction time for the syntheses of the target compounds was reduced. Subsequently, Ellman's modified method was used to evaluate the enzyme inhibitory activity of the synthesized structures. It was observed that most hybrid structures were moderate to potent inhibitors of AChE compared to Tacrine as the reference drug among which 7f with 4-fluorophenyl substituent was the most active compound (IC50=5 nM).

Keywords: Alzheimer's disease; Cholinesterase inhibitor; Coumarin; Docking study; Tacrine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / chemistry
  • Benzopyrans / pharmacology
  • Binding Sites
  • Butyrylcholinesterase / metabolism*
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Coumarins / chemistry
  • Coumarins / pharmacology
  • Drug Design*
  • Enzyme Activation / drug effects
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship
  • Tacrine / chemistry
  • Tacrine / pharmacology


  • Benzopyrans
  • Cholinesterase Inhibitors
  • Coumarins
  • Tacrine
  • coumarin
  • Acetylcholinesterase
  • Butyrylcholinesterase