Design, synthesis, and evaluation of genipin derivatives for the treatment of Alzheimer's Disease

Chem Biol Drug Des. 2019 Feb;93(2):110-122. doi: 10.1111/cbdd.13194. Epub 2018 Nov 28.

Abstract

Twenty-two novel genipin derivatives have been designed, synthesized, and evaluated for their inhibitory activity against acetylcholinesterase (AChE). As a result, compound 13a bearing ligustrazine moiety displayed the most potent AChE inhibitory activity in this series with IC50 value of 218 nm. Besides, MTT assay was performed to investigate the neuroprotection of these compounds against PC12 cells injured by Amyloid β-protein 1-42 (Aβ1-42 ). Among them, 8a showed higher inhibition rate (%Inhibition = 22.29) than the positive reference Donepezil (%Inhibition = 17.65).

Keywords: Alzheimer's disease; acetylcholinesterase inhibitors; genipin derivatives; neuroprotection; synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism
  • Alzheimer Disease
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Binding Sites
  • Cell Survival / drug effects
  • Drug Design*
  • Inhibitory Concentration 50
  • Iridoids / chemistry*
  • Iridoids / metabolism
  • Iridoids / pharmacology
  • Iridoids / therapeutic use
  • Molecular Docking Simulation
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • PC12 Cells
  • Peptide Fragments / toxicity
  • Protein Structure, Tertiary
  • Rats
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Iridoids
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • genipin
  • Acetylcholinesterase