Caffeic acid phenethyl ester (CAPE)-derivatives act as selective inhibitors of acetylcholinesterase

Eur J Med Chem. 2019 Sep 1:177:259-268. doi: 10.1016/j.ejmech.2019.05.059. Epub 2019 May 26.

Abstract

Unexpected inhibitory effects against eeAChE could be found for a newly synthesized class of caffeic acid phenethyl ester (CAPE) derivatives. Thus, phenethyl-(E)-3-(3,5-dimethoxy-4-phenethoxyphenyl)-acrylate (Ki = 1.97 ± 0.38 μM, Ki´ = 2.44 ± 0.07 μM) and 4-(2-(((E)-3-(3,4-bis(benzyloxy)phenyl)acryloyl)oxy)ethyl)-1,2-phenylene (2E,2'E)-bis(3-(3,4-bis(benzyloxy)phenyl)acrylate) (Ki = 0.72 ± 0.31 μM, Ki´ = 1.80 ± 0.21 μM) showed very good inhibition of eeAChE, while being non cytotoxic for malignant human cancer cells and non-malignant mouse fibroblasts. Also, they are weak inhibitors for BChE (from equine serum).

Keywords: Acetylcholinesterase; Butyrylcholinesterase; Caffeic acid phenethyl ester; Cinnamic acid phenethyl esters; Inhibitors.

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism
  • Animals
  • Butyrylcholinesterase / metabolism
  • Caffeic Acids / chemical synthesis
  • Caffeic Acids / chemistry
  • Caffeic Acids / pharmacology*
  • Caffeic Acids / toxicity
  • Catalytic Domain
  • Cell Line, Tumor
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Cholinesterase Inhibitors / toxicity
  • Electrophorus
  • Horses
  • Humans
  • Mice
  • Molecular Docking Simulation
  • NIH 3T3 Cells
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / chemical synthesis
  • Phenylethyl Alcohol / pharmacology*
  • Phenylethyl Alcohol / toxicity

Substances

  • Caffeic Acids
  • Cholinesterase Inhibitors
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Phenylethyl Alcohol