Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/173447
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DC Field | Value | Language |
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dc.contributor.author | Viayna, Elisabet | - |
dc.contributor.author | Coquelle, Nicolas | - |
dc.contributor.author | Cieslikiewicz-Bouet, Monika | - |
dc.contributor.author | Cisternas, Pedro | - |
dc.contributor.author | Oliva, Carolina | - |
dc.contributor.author | Sánchez-López, E. (Elena) | - |
dc.contributor.author | Ettcheto Arriola, Miren | - |
dc.contributor.author | Bartolini, Manuela | - |
dc.contributor.author | De Simone, Angela | - |
dc.contributor.author | Ricchini, Mattia | - |
dc.contributor.author | Rendina, Marisa | - |
dc.contributor.author | Pons, Mégane | - |
dc.contributor.author | Firuzi, Omidreza | - |
dc.contributor.author | Pérez, Belén | - |
dc.contributor.author | Saso, Luciano | - |
dc.contributor.author | Andrisano, Vincenza | - |
dc.contributor.author | Nachon, Florian | - |
dc.contributor.author | Brazzolotto, Xavier | - |
dc.contributor.author | García, Maria Luisa | - |
dc.contributor.author | Camins Espuny, Antoni | - |
dc.contributor.author | Silman, Israel | - |
dc.contributor.author | Jean, Ludovic | - |
dc.contributor.author | Inestrosa, Nibaldo C. | - |
dc.contributor.author | Colletier, Jacques-Philippe | - |
dc.contributor.author | Renard, Pierre-Yves | - |
dc.contributor.author | Muñoz-Torrero López-Ibarra, Diego | - |
dc.date.accessioned | 2021-01-28T11:38:56Z | - |
dc.date.available | 2022-12-31T06:10:19Z | - |
dc.date.issued | 2021 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | http://hdl.handle.net/2445/173447 | - |
dc.description.abstract | Combination of the scaffolds of the cholinesterase inhibitor huprine Y and the antioxidant capsaicin results in compounds with nanomolar potencies toward human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) that retain or improve the antioxidant properties of capsaicin. Crystal structures of their complexes with AChE and BChE revealed the molecular basis for their high potency. Brain penetration was confirmed by biodistribution studies in C57BL6 mice, with one compound (5i) displaying better brain/plasma ratio than donepezil. Chronic treatment of 10 month-old APP/PS1 mice with 5i (2 mg/kg, ip, 3 times per week, 4 weeks) rescued learning and memory impairments, as measured by 3 different behavioral tests, delayed the Alzheimer-like pathology progression, as suggested by a significantly reduced Aβ42/Aβ40 ratio in hippocampus, improved basal synaptic efficacy, and significantly reduced hippocampal oxidative stress and neuroinflammation. Compound 5i emerges as an interesting anti-Alzheimer lead with beneficial effects on cognitive symptoms and on some underlying disease mechanisms. | - |
dc.format.extent | 28 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Chemical Society | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1021/acs.jmedchem.0c01775 | - |
dc.relation.ispartof | Journal of Medicinal Chemistry, 2021, vol. 64, num. 1, p. 812-839 | - |
dc.relation.uri | https://doi.org/10.1021/acs.jmedchem.0c01775 | - |
dc.rights | (c) American Chemical Society , 2021 | - |
dc.source | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) | - |
dc.subject.classification | Malalties neuromusculars | - |
dc.subject.classification | Sistema nerviós central | - |
dc.subject.classification | Acetilcolinesterasa | - |
dc.subject.other | Neuromuscular diseases | - |
dc.subject.other | Central nervous system | - |
dc.subject.other | Acetylcholinesterase | - |
dc.title | Discovery of a Potent Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase with Antioxidant Activity that Alleviates Alzheimer-like Pathology in Old APP/PS1 Mice | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 705872 | - |
dc.date.updated | 2021-01-28T11:38:56Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
Files in This Item:
File | Description | Size | Format | |
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705872.pdf | 4.19 MB | Adobe PDF | View/Open |
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