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

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 21; p. 5009
• Main Authors: Camarillo-López, Raúl Horacio, Hernández Rodríguez, Maricarmen, Torres-Ramos, Mónica Adriana, Arciniega-Martínez, Ivonne Maciel, García-Marín, Iohanan Daniel, Correa Basurto, José, Méndez Méndez, Juan Vicente, Rosales-Hernández, Martha Cecilia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29-10-2020; MDPI
• Subjects: Acetylcholinesterase; Acids; Alzheimer Disease - chemically induced; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer Disease - prevention & control; Alzheimer's disease; amyloid beta peptide (Aβ1-42); Amyloid beta-Peptides - metabolism; Amyloidogenesis; Animals; Apoptosis; astrocyte cells; Astrocytes; Astrocytes - metabolism; Astrocytes - pathology; Bioavailability; Brain; Carbamates - chemistry; Carbamates - pharmacology; Cell death; Chromatography; Cytokines; Disease Models, Animal; Fibrillogenesis; Free radicals; Galantamine; Humans; In vivo methods and tests; M4 compound; Microscopy; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Peptide Fragments - metabolism; Peptides; Polyphenols; Proteins; Rats; Scopolamine; Scopolamine - adverse effects; Scopolamine - pharmacology; Secretase; Tumor necrosis factor-α; β-Amyloid; β-secretase; β-secretase; Alzheimer’s disease; astrocyte cells; M4 compound; scopolamine; amyloid beta peptide (Aβ1-42)
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25215009

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
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 Aβ
. This work first aimed to assess in in vitro studies to see whether the death of astrocyte cells promoted by Aβ
could be prevented. Second, our work investigated the ability of the
compound to inhibit amyloidogenesis using an in vivo model after scopolamine administration. The results showed that
possesses a moderate protective effect in astrocytes against Aβ
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
was observed in comparison with a galantamine model employed in rats, in which case this outcome was attributed to the bioavailability of
in the brain of the rats.