Highly Significant Scaffolds to Design and Synthesis Cholinesterase Inhibitors as Anti-Alzheimer Agents

Mini Rev Med Chem. 2019;19(19):1577-1598. doi: 10.2174/1389557519666190719143112.

Abstract

Alzheimer, a progressive disease, is a common term for memory loss which interferes with daily life through severe influence on cognitive abilities. Based on the cholinergic hypothesis, and Xray crystallographic determination of the structure of acetylcholinesterase (AChE) enzyme, the level of acetylcholine (ACh, an important neurotransmitter associated with memory) in the hippocampus and cortex area of the brain has a direct effect on Alzheimer. This fact encourages scientists to design and synthesize a wide range of acetylcholinesterase inhibitors (AChEIs) to control the level of ACh in the brain, keeping in view the crystallographic structure of AChE enzyme and drugs approved by the Food and Drug Administration (FDA). AChEIs have slightly diverse pharmacological properties, but all of them work by inhibiting the segregation of ACh by blocking AChE. We reviewed significant scaffolds introduced as AChEIs. In some studies, the activity against butyrylcholinesterase (BuChE) has been evaluated as well because BuChE is a similar enzyme to neuronal acetylcholinesterase and is capable of hydrolyzing ACh. In order to study AChEIs effectively, we divided them structurally into 12 classes and briefly explained effective AChEIs and compared their activities against AChE enzyme.

Keywords: Alzheimer disease; Cholinesterase inhibitors; acetylcholine; dementia; design; synthesis..

Publication types

  • Review

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism
  • Alkaloids / chemical synthesis
  • Alkaloids / chemistry
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Butyrylcholinesterase / chemistry
  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / therapeutic use
  • Donepezil / chemical synthesis
  • Donepezil / chemistry
  • Drug Design*
  • Humans
  • Rivastigmine / chemical synthesis
  • Rivastigmine / chemistry
  • Tacrine / chemical synthesis
  • Tacrine / chemistry

Substances

  • Alkaloids
  • Cholinesterase Inhibitors
  • Tacrine
  • Donepezil
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Rivastigmine