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

Raúl Horacio Camarillo-López, Maricarmen Hernández Rodríguez, Mónica Adriana Torres-Ramos, Ivonne Maciel Arciniega-Martínez, Iohanan Daniel García-Marín, José Correa Basurto, Juan Vicente Méndez Méndez, Martha Cecilia Rosales-Hernández

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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.

Original languageEnglish
JournalMolecules (Basel, Switzerland)
Volume25
Issue number21
DOIs
StatePublished - 29 Oct 2020

Keywords

  • Alzheimer’s disease
  • M4 compound
  • amyloid beta peptide (Aβ1-42)
  • astrocyte cells
  • scopolamine
  • β-secretase

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