Ionic liquid mediated synthesis and molecular docking study of novel aromatic embedded Schiff bases as potent cholinesterase inhibitors

Bioorg Chem. 2014 Dec:57:162-168. doi: 10.1016/j.bioorg.2014.10.005. Epub 2014 Nov 4.

Abstract

Novel aromatic embedded Schiff bases have been synthesized in ionic liquid [bmim]Br and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibitory activities. Among the newly synthesized compounds, 5f, 5h and 7j displayed higher AChE enzyme inhibitory activities than standard drug, galanthamine, with IC50 values of 1.88, 2.05 and 2.03μM, respectively. Interestingly, all the compounds except for compound 5c displayed higher BChE inhibitories than standard with IC50 values ranging from 3.49 to 19.86μM. Molecular docking analysis for 5f and 7j possessing the most potent AChE and BChE inhibitory activities, disclosed their binding interaction templates to the active site of AChE and BChE enzymes, respectively.

Keywords: AChE and BChE; Galanthamine; Ionic liquids; Schiff base.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology
  • Animals
  • Butyrylcholinesterase / chemistry
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Crystallography, X-Ray
  • Humans
  • Hydrocarbons, Aromatic / chemical synthesis
  • Hydrocarbons, Aromatic / chemistry
  • Hydrocarbons, Aromatic / pharmacology
  • Ionic Liquids / chemistry*
  • Molecular Docking Simulation
  • Schiff Bases / chemical synthesis
  • Schiff Bases / chemistry*
  • Schiff Bases / pharmacology*
  • Structure-Activity Relationship
  • Torpedo

Substances

  • Cholinesterase Inhibitors
  • Hydrocarbons, Aromatic
  • Ionic Liquids
  • Schiff Bases
  • Acetylcholinesterase
  • Butyrylcholinesterase