Donepezil-based multi-functional cholinesterase inhibitors for treatment of Alzheimer's disease

Eur J Med Chem. 2018 Oct 5:158:463-477. doi: 10.1016/j.ejmech.2018.09.031. Epub 2018 Sep 13.

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in elderly people. Considering the multifactorial nature of AD, the concept of multi-target-directed ligands (MTDLs) has recently emerged as a new strategy for designing therapeutic agents on AD. MTDLs are confirmed to simultaneously affect diverse targets which contribute to etiology of AD. As the most potent approved drug, donepezil affects various events of AD, like inhibiting cholinesterases activities, anti-Aβ aggregation, anti-oxidative stress et al. Modifications of donepezil or hybrids with pharmacophores of donepezil in recent five years are summarized in this article. On the basis of case studies, our concerns and opinions about development of donepezil derivatives, designing of MTDLs, and perspectives for AD treatments are discussed in final part.

Keywords: Alzheimer's disease; Donepezil; Multi-target-directed ligands (MTDLs).

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Cholinesterase Inhibitors / therapeutic use
  • Cholinesterases / chemistry
  • Cholinesterases / metabolism
  • Donepezil
  • Drug Discovery
  • Humans
  • Indans / chemistry*
  • Indans / pharmacology*
  • Indans / therapeutic use
  • Ligands
  • Molecular Docking Simulation
  • Oxidative Stress / drug effects
  • Piperidines / chemistry*
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use

Substances

  • Amyloid beta-Peptides
  • Cholinesterase Inhibitors
  • Indans
  • Ligands
  • Piperidines
  • Donepezil
  • Cholinesterases