New multifunctional AChE inhibitor drug prototypes protect against Aβ-induced memory deficit

Neurol Sci. 2020 Feb;41(2):451-455. doi: 10.1007/s10072-019-04036-6. Epub 2019 Sep 11.

Abstract

Alzheimer's disease (AD) is the most incident neurodegenerative disorder, characterized by accumulation of extracellular amyloid-β (Aβ), intracellular neurofibrillary tangles, and cognitive impairment. The current available treatments are mainly based on the use of reversible acetylcholinesterase (AChE) inhibitors, which only ameliorate the cognitive deficits. However, it is important to develop disease-modifying drugs with neuroprotective effects in order to hamper the progression of the disease. Here, we describe the effect of four promising new drugs with additional protective characteristics on AD-associated memory changes. C57Bl/6 mice treated with the compounds received an intra-hippocampal injection of Aβ1-40 and were submitted to the novel object recognition test, to evaluate memory recovery. All the compounds prevented memory loss. Compounds PQM-56 (4c) and PQM-67 (4g) showed the best profile of memory recovery, representing potential drug candidates for AD treatment.

Keywords: Alzheimer’s disease; Amyloid-β; Memory; N-benzyl-piperidine-aryl-acylhydrazone derivatives.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cholinesterase Inhibitors / pharmacology*
  • Cognition Disorders / drug therapy
  • Disease Models, Animal
  • Memory / drug effects*
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy*
  • Mice, Inbred C57BL
  • Neuroprotective Agents / therapeutic use
  • Peptide Fragments / pharmacology

Substances

  • Amyloid beta-Peptides
  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Peptide Fragments