Substituted cinnamic anhydrides act as selective inhibitors of acetylcholinesterase

Bioorg Chem. 2019 Sep:90:103058. doi: 10.1016/j.bioorg.2019.103058. Epub 2019 Jun 8.

Abstract

Cinnamic anhydrides have been shown to be more than reactive reagents, but they also act as inhibitors of the enzyme acetylcholinesterease (AChE). Thus, out of a set of 33 synthesised derivatives, several of them were mixed type inhibitors for AChE (from electric eel). Thus, (E)-3-(2,4-dimethoxyphenyl)acrylic anhydride (2c) showed Ki = 8.30 ± 0.94 µM and Ki' = 9.54 ± 0.38 µM, and for (E)-3-(3-chlorophenyl)acrylic anhydride (2u) Ki = 8.23 ± 0.93 µM and Ki' = 13.07 ± 0.46 µM were measured. While being not cytotoxic to many human cell lines, these compounds showed an unprecedented and noteworthy inhibitory effect for AChE but not for butyrylcholinesterase (BChE).

Keywords: Acetylcholinesterase; Butyrylcholinesterase; Cinnamic anhydrides; Inhibitors.

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Butyrylcholinesterase / chemistry*
  • Cell Proliferation
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Cinnamates / chemistry*
  • Ethylene Oxide / analogs & derivatives
  • Ethylene Oxide / chemistry
  • Ethylene Oxide / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Protein Conformation
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Cholinesterase Inhibitors
  • Cinnamates
  • cinnamic anhydride
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Ethylene Oxide