Arylaminopropanone Derivatives as Potential Cholinesterase Inhibitors: Synthesis, Docking Study and Biological Evaluation

Molecules. 2020 Apr 10;25(7):1751. doi: 10.3390/molecules25071751.

Abstract

Neurodegenerative diseases in which the decrease of the acetylcholine is observed are growing worldwide. In the present study, a series of new arylaminopropanone derivatives with N-phenylcarbamate moiety (1-16) were prepared as potential acetylcholinesterase and butyrylcholinesterase inhibitors. In vitro enzyme assays were performed; the results are expressed as a percentage of inhibition and the IC50 values. The inhibitory activities were compared with reference drugs galantamine and rivastigmine showing piperidine derivatives (1-3) as the most potent. A possible mechanism of action for these compounds was determined from a molecular modelling study by using combined techniques of docking, molecular dynamics simulations and quantum mechanics calculations.

Keywords: N-phenylcarbamate; acetylcholinesterase; arylaminopropanone; butyrylcholinesterase; enzyme assays; molecular modelling.

MeSH terms

  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Enzyme Activation / drug effects
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Propanolamines / chemical synthesis
  • Propanolamines / chemistry*
  • Propanolamines / pharmacology*
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Propanolamines