Quinoxalinetacrine QT78, a cholinesterase inhibitor as a potential ligand for Alzheimer’s disease therapy

We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer’s disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 _M...

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Detalles Bibliográficos
Autores: Ramos, Eva, Palomino-Antolín, Alejandra, Bartolini, Manuela, Iriepa, Isabel, Moraleda, Ignacio, Diez-Iriepa, Daniel, Samadi, Abdelouahid, Cortina, Carol V., Chioua, Mourad, Egea, Javier, Romero, Alejandro, Marco-Contelles, José
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/691168
Acceso en línea:http://hdl.handle.net/10486/691168
https://dx.doi.org/10.3390/molecules24081503
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease
Cholinesterase inhibitor
Hepatotoxicity
Molecular modeling
Neuroprotection
Quinoxalines
Quinoxalinetacrines
Tacrine
Farmacia
Descripción
Sumario:We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer’s disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 _M to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC50 (hAChE) = 22.0 _ 1.3 _M; IC50 (hBuChE) = 6.79 _ 0.33 _M). Moreover, QT78 showed e_ective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A

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