Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/177730
COMPARTIR / EXPORTAR:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Invitar a revisión por pares abierta
Título

Tau-Centric Multitarget Approach for Alzheimer's Disease: Development of First-in-Class Dual Glycogen Synthase Kinase 3β and Tau-Aggregation Inhibitors

AutorGandini, A.; Bartolini, M.; Tedesco, D.; Martínez-González, Loreto CSIC ORCID ; Roca, Carlos CSIC ORCID; Campillo, Nuria E. CSIC ORCID ; Zaldívar-Díez, Josefa CSIC ORCID; Pérez, Concepción CSIC ORCID; Zuccheri, G.; Miti, Andrea; Feoli, A.; Castellano, S.; Petralla, Sabrina; Monti, B.; Rossi, M.; Moda, F.; Legname, G.; Martínez Gil, Ana CSIC ORCID ; Bolognesi, Maria Laura
Fecha de publicación2018
EditorAmerican Chemical Society
CitaciónJournal of Medicinal Chemistry 61: 7640-7656 (2018)
ResumenSeveral findings propose the altered tau protein network as an important target for Alzheimer's disease (AD). Particularly, two points of pharmacological intervention can be envisaged: inhibition of phosphorylating tau kinase GSK-3β and tau aggregation process. On the basis of this consideration and on our interest in multitarget paradigms in AD, we report on the discovery of 2,4-thiazolidinedione derivatives endowed with such a profile. 28 and 30 displayed micromolar IC values toward GSK-3β, together with the capacity of inhibiting AcPHF6 aggregation of 60% and 80% at 10 μM, respectively. In addition, they showed PAMPA-BBB permeability, together with a suitable cellular safety profile. 30 also displayed inhibition of both K18 and full-length tau aggregations. Finally, both compounds were able to improve cell viability in an okadaic acid-induced neurodegeneration cell model. To the best of our knowledge, 28 and 30 are the first balanced, nontoxic, dual-acting compounds hitting tau cascade at two different hubs.
Versión del editorhttp://dx.doi.org/10.1021/acs.jmedchem.8b00610
URIhttp://hdl.handle.net/10261/177730
DOI10.1021/acs.jmedchem.8b00610
Identificadoresdoi: 10.1021/acs.jmedchem.8b00610
issn: 0022-2623
e-issn: 1520-4804
Aparece en las colecciones: (IQM) Artículos
(CIB) Artículos




Ficheros en este ítem:
Fichero Descripción Tamaño Formato
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo

CORE Recommender

SCOPUSTM   
Citations

76
checked on 12-mar-2024

WEB OF SCIENCETM
Citations

73
checked on 29-feb-2024

Page view(s)

229
checked on 18-mar-2024

Download(s)

38
checked on 18-mar-2024

Google ScholarTM

Check

Altmetric

Altmetric


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.