Tert-butyl-(4-hydroxy-3-((3-(2-methylpiperidin-yl)propyl)carbamoyl)phenyl)carbamate Has Moderated Protective Activity in Astrocytes Stimulated with Amyloid Beta 1-42 and in a Scopolamine Model

Molecules. 2020 Oct 29;25(21):5009. doi: 10.3390/molecules25215009.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease with no cure nowadays; there is no treatment either to prevent or to stop its progression. In vitro studies suggested that tert-butyl-(4-hydroxy-3-((3-(2-methylpiperidin-yl)propyl)carbamoyl)phenyl) carbamate named the M4 compound can act as both β-secretase and an acetylcholinesterase inhibitor, preventing the amyloid beta peptide (Aβ) aggregation and the formation of fibrils (fAβ) from Aβ1-42. This work first aimed to assess in in vitro studies to see whether the death of astrocyte cells promoted by Aβ1-42 could be prevented. Second, our work investigated the ability of the M4 compound to inhibit amyloidogenesis using an in vivo model after scopolamine administration. The results showed that M4 possesses a moderate protective effect in astrocytes against Aβ1-42 due to a reduction in the TNF-α and free radicals observed in cell cultures. In the in vivo studies, however, no significant effect of M4 was observed in comparison with a galantamine model employed in rats, in which case this outcome was attributed to the bioavailability of M4 in the brain of the rats.

Keywords: Alzheimer’s disease; M4 compound; amyloid beta peptide (Aβ1-42); astrocyte cells; scopolamine; β-secretase.

MeSH terms

  • Alzheimer Disease* / chemically induced
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Alzheimer Disease* / prevention & control
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Carbamates* / chemistry
  • Carbamates* / pharmacology
  • Disease Models, Animal
  • Humans
  • Neuroprotective Agents* / chemistry
  • Neuroprotective Agents* / pharmacology
  • Peptide Fragments / metabolism*
  • Rats
  • Scopolamine / adverse effects*
  • Scopolamine / pharmacology

Substances

  • Amyloid beta-Peptides
  • Carbamates
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Scopolamine