α-bisabolol β-D-fucopyranoside as a potential modulator of β-amyloid peptide induced neurotoxicity: An in vitro &in silico study

Bioorg Chem. 2019 Jul;88:102935. doi: 10.1016/j.bioorg.2019.102935. Epub 2019 Apr 19.

Abstract

Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder affecting the elderly people. For the AD treatment, there is inefficiency in the existing medication, as these drugs reduce only the symptoms of the disease. Since multiple pathological proteins are involved in the development of AD, searching for a single molecule targeting multiple AD proteins will be a new strategy for the management of AD. In view of this, the present study was designed to synthesize and evaluate the multifunctional neuroprotective ability of the sesquiterpene glycoside α-bisabolol β-D-fucopyranoside (ABFP) against multiple targets like acetylcholinesterase, oxidative stress and β-amyloid peptide aggregation induced cytotoxicity. In silico computational docking and simulation studies of ABFP with acetylcholinesterase (AChE) showed that it can interact with Asp74 and Thr75 residues of the enzyme. The in vitro studies showed that the compound possess significant ability to inhibit the AChE enzyme apart from exhibiting antioxidant, anti-aggregation and disaggregation properties. In addition, molecular dynamics simulation studies proved that the interacting residue between Aβ peptide and ABFP was found to be involved in Leu34 and Ile31. Furthermore, the compound was able to protect the Neuro2 a cells against Aβ25-35 peptide induced toxicity. Overall, the present study evidently proved ABFP as a neuroprotective agent, which might act as a multi-target compound for the treatment of Alzheimer's disease.

Keywords: Alzheimer’s disease (AD); Amyloid β-protein; Cholinesterase (ChE); Neuroprotective; Oxidative Stress; α-bisabolol β-D-fucopyranoside (ABFP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Biphenyl Compounds / antagonists & inhibitors
  • Biphenyl Compounds / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Fucose / analogs & derivatives
  • Fucose / chemistry
  • Fucose / pharmacology*
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Monocyclic Sesquiterpenes / chemical synthesis
  • Monocyclic Sesquiterpenes / chemistry
  • Monocyclic Sesquiterpenes / pharmacology*
  • Picrates / antagonists & inhibitors
  • Picrates / metabolism
  • Protein Aggregates / drug effects
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Biphenyl Compounds
  • Cholinesterase Inhibitors
  • Monocyclic Sesquiterpenes
  • Picrates
  • Protein Aggregates
  • bisabolol
  • Fucose
  • 1,1-diphenyl-2-picrylhydrazyl
  • Acetylcholinesterase