Amino derivatives of platanic acid act as selective and potent inhibitors of butyrylcholinesterase

Eur J Med Chem. 2017 Jan 27:126:652-668. doi: 10.1016/j.ejmech.2016.11.056. Epub 2016 Nov 30.

Abstract

A set of thirtyfive 30-norlupan derivatives (2-36) was prepared from the natural triterpenoid platanic acid (PA), and the hydroxyl group at C-3, the carboxyl group at C-17 and the carbonyl group at C-20 were modified. These derivatives were tested for their inhibitory activity for the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum) using Ellman's assay. Extra enzyme kinetic studies were performed. The most active compound was (3β, 20R)-3-acetyloxy-20-amino-30-norlupan-28-oate (32) showing a Ki value of 0.01 ± 0.003 μM for BChE. This compound proved to be a selective (FB = 851), mixed-type inhibitor for BChE.

Keywords: Acetylcholinesterase; Butyrylcholinesterase; Platanic acid; Triterpenes.

MeSH terms

  • Animals
  • Butyrylcholinesterase / drug effects*
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Electrophorus
  • Horses
  • Kinetics
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • Cholinesterase Inhibitors
  • Triterpenes
  • platanic acid
  • Butyrylcholinesterase