Novel 12-hydroxydehydroabietylamine derivatives act as potent and selective butyrylcholinesterase inhibitors

Bioorg Chem. 2019 Sep:90:103092. doi: 10.1016/j.bioorg.2019.103092. Epub 2019 Jul 2.

Abstract

The skeleton of the diterpene dehydroabietylamine was modified, and a set of 12-hydroxy-dehydroabietylamine derivatives was obtained. The compounds were screened in colorimetric Ellman's assays to determine their ability to act as inhibitors for the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). Additional investigations concerning the enzyme kinetics were performed and showed 12-hydroxy-N-(4-nitro-benzoyl)dehydroabietylamine (13) and 12-hydroxy-N-(isonicotinoyl)dehydroabietylamine (17) as selective BChE inhibitors holding good inhibition constants Ki = 0.72 ± 0.06 μM and Ki = 0.86 ± 0.19 μM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Animals
  • Butyrylcholinesterase / chemistry*
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Diterpenes / chemistry*
  • Diterpenes / pharmacology*
  • Electrophorus
  • Ethylamines / chemistry
  • Ethylamines / pharmacology*
  • Molecular Docking Simulation
  • Structure-Activity Relationship

Substances

  • 12-Hydroxy-N-(isonicotinoyl)dehydroabietylamine
  • Cholinesterase Inhibitors
  • Diterpenes
  • Ethylamines
  • Acetylcholinesterase
  • Butyrylcholinesterase