Novel carbamate derivatives as selective butyrylcholinesterase inhibitors

Bioorg Chem. 2018 Aug:78:29-38. doi: 10.1016/j.bioorg.2018.03.003. Epub 2018 Mar 3.

Abstract

Selective butyrylcholinesterase inhibitors could be the promising drug candidates, used in treatment of Alzheimer's disease. The study describes the synthesis and biological activity of novel carbamate derivatives with N-phenylpiperazine, N-benzylpiperazine and 4-benzylpiperidine moieties. Biological studies revealed that most of these compounds displayed significant activity against BuChE. Compound 16 (3-(4-phenyl-piperazin-1-ylmethyl)-phenyl phenylcarbamate) turned out to be the most active (IC50 = 2.00 μM for BuChE). For all synthesized compounds lipophilicity and other physicochemical properties were calculated using computer programs. Relationship between these properties and activity was also checked. Binding mode with enzyme and the ensuing differences in activity were explained by the molecular modeling studies.

Keywords: Biological evaluation; Butyrylcholinesterase; Carbamates; Docking studies; Inhibitor; Physicochemical properties; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Butyrylcholinesterase / metabolism*
  • Carbamates / chemical synthesis
  • Carbamates / chemistry
  • Carbamates / pharmacology*
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrophorus
  • Horses
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Carbamates
  • Cholinesterase Inhibitors
  • Acetylcholinesterase
  • Butyrylcholinesterase