Design, synthesis, molecular modeling and anticholinesterase activity of benzylidene-benzofuran-3-ones containing cyclic amine side chain

Future Med Chem. 2017 May;9(7):659-671. doi: 10.4155/fmc-2016-0237. Epub 2017 May 9.

Abstract

Aim: A series of 2-benzylidene-benzofuran-3-ones were designed from the structures of Ebselen analogs and aurone derivatives and synthesized in good yields.

Materials & methods: The target compounds were prepared by the condensation reaction between appropriate benzofuranones with amino alkoxy aldehydes and evaluated as cholinesterase inhibitors by Ellman's method.

Results: The in vitro anti-acetylcholinesterase (AChE)/butyrylcholinesterase activities of the synthesized compounds revealed that 7e (IC50 = 0.045 μM) is the most active compound against AChE. Furthermore, the docking study confirmed the results obtained through in vitro experiments and predicted the possible binding conformation.

Conclusion: The anticholinesterase activities of benzylidene-benzofurane-3-ones as aurone analogs revealed that the compounds bearing piperidinylethoxy residue showed better activities against AChE, introducing these compounds for further drug discovery developments. [Formula: see text].

Keywords: Alzheimer’s disease; acetylcholinesterase inhibitors; benzofuran-3-one.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Benzofurans / chemical synthesis*
  • Benzofurans / chemistry
  • Benzofurans / metabolism
  • Benzofurans / pharmacology*
  • Benzylidene Compounds / chemical synthesis*
  • Benzylidene Compounds / chemistry
  • Benzylidene Compounds / pharmacology*
  • Binding Sites
  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Inhibitors / pharmacology*
  • Drug Design
  • Drug Discovery
  • Humans
  • Kinetics
  • Models, Molecular
  • Molecular Docking Simulation
  • Structure-Activity Relationship

Substances

  • 2-(4-(2-(piperidin-1-yl)ethoxy)benzylidene)-6-ethoxybenzofuran-3(2H)-one
  • Benzofurans
  • Benzylidene Compounds
  • Cholinesterase Inhibitors
  • aurone
  • Acetylcholinesterase
  • Butyrylcholinesterase