Synthesis, Characterization, and Evaluation of Difluoropyrido[4,3-b]indoles as Potential Agents for Acetylcholinesterase and Antiamnesic Activity

Arch Pharm (Weinheim). 2017 Apr;350(3-4). doi: 10.1002/ardp.201600303. Epub 2017 Mar 22.

Abstract

Acetylcholinesterase (AChE) inhibitors are currently the most widely prescribed drugs for Alzheimer's disease. The high potential of indole compounds in medicinal chemistry led us to discover a novel series of fluoroindole compounds. The synthesis and pharmacological analysis of the difluoropyrido[4,3-b]indoles 11-34 are described. Compounds 11-34 were tested for AChE inhibition activity using a rat brain homogenate. Compounds 25-29 display a promising in vitro profile with an IC50 value range of 46-51.6 nM and show significant protective effect on scopolamine-induced amnesia. The present data indicate that compounds 25-29 may represent attractive potent molecules for the treatment of Alzheimer's disease.

Keywords: Acetylcholinesterase; Alzheimer's disease; Antiamnesic activity; Difluoropyrido[4,3-b]indoles.

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Amnesia / drug therapy*
  • Animals
  • CHO Cells
  • Carbolines / chemical synthesis
  • Carbolines / chemistry
  • Carbolines / pharmacology*
  • Cells, Cultured
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Carbolines
  • Cholinesterase Inhibitors
  • Acetylcholinesterase