l-Hypaphorine and d-hypaphorine: Specific antiacetylcholinesterase activity in rat brain tissue

Bioorg Med Chem Lett. 2021 Sep 1:47:128206. doi: 10.1016/j.bmcl.2021.128206. Epub 2021 Jun 16.

Abstract

Acetylcholinesterase (AChEis) inhibitors are used to treat neurodegenerative diseases like Alzheimer's disease (AD). l-Hypaphorine (l-HYP) is a natural indole alkaloid that has been shown to have effects on the central nervous system (CNS). The goal of this research was to synthesize l-HYP and d-HYP and test their anticholinesterasic properties in rat brain regions. l-HYP suppressed acetylcholinesterase (AChE) activity only in the cerebellum, whereas d-HYP inhibited AChE activity in all CNS regions studied. No cytotoxic effect on normal human cells (HaCaT) was observed in the case of l-HYP and d-HYP although an increase in cell proliferation. Molecular modeling studies revealed that d-HYP and l-HYP have significant differences in their binding mode positions and interact stereospecifically with AChE's amino acid residues.

Keywords: Acetylcholinesterase; Betaine; Indole; Neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Brain / enzymology*
  • Brain / pathology
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Molecular Structure
  • Rats
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Indoles
  • Acetylcholinesterase
  • lenticin