Isolation of cholinesterase and β-secretase 1 inhibiting compounds from Lycopodiella cernua

Bioorg Med Chem. 2015 Jul 1;23(13):3126-34. doi: 10.1016/j.bmc.2015.04.080. Epub 2015 May 6.

Abstract

Three new serratene-type triterpenoids (1-3) and a new hydroxy unsaturated fatty acid (13) together with nine known compounds (4-12) were isolated from Lycopodiella cernua. The chemical structures were established using NMR, MS, and Mosher's method. Compound 13 showed the most potent inhibitory activity against acetylcholinesterase (AChE) with an IC50 value of 0.22μM. For butyrylcholinesterase (BChE) inhibitory activity, 5 showed the most potent activity with an IC50 value of 0.42μM. Compound 2 showed the most potent activity with an IC50 of 0.23μM for BACE-1 inhibitory activity. The kinetic activities were investigated to determine the type of enzyme inhibition involved. The types of AChE inhibition shown by compounds 4, 5, and 13 were mixed; BChE inhibition by 5 was competitive, while 2 and 6 showed mixed-types. In addition, molecular docking studies were performed to investigate the interaction of these compounds with the pocket sites of AChE. The docking results revealed that the tested inhibitors 3, 4, and 13 were stably present in several pocket domains of the AChE residue.

Keywords: Cholinesterase; Hydroxy unsaturated fatty acid; Lycopodiella cernua; Serratene-type triterpenoids; β-Secretase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid Precursor Protein Secretases / chemistry
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / chemistry
  • Butyrylcholinesterase / chemistry*
  • Catalytic Domain
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / isolation & purification
  • Fatty Acids, Unsaturated / chemistry
  • Fatty Acids, Unsaturated / isolation & purification
  • Humans
  • Kinetics
  • Lycopodiaceae / chemistry*
  • Molecular Docking Simulation
  • Molecular Structure
  • Plant Extracts / chemistry
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / isolation & purification
  • Protein Binding
  • Structure-Activity Relationship
  • Triterpenes / chemistry*
  • Triterpenes / isolation & purification

Substances

  • Cholinesterase Inhibitors
  • Fatty Acids, Unsaturated
  • Plant Extracts
  • Protease Inhibitors
  • Triterpenes
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human