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...
| Autores: | , , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Data de publicação: | 2019 |
| País: | España |
| Recursos: | Universidad Autónoma de Madrid |
| Repositório: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglês |
| OAI Identifier: | oai:repositorio.uam.es:10486/691168 |
| Acesso em linha: | http://hdl.handle.net/10486/691168 https://dx.doi.org/10.3390/molecules24081503 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Alzheimer’s disease Cholinesterase inhibitor Hepatotoxicity Molecular modeling Neuroprotection Quinoxalines Quinoxalinetacrines Tacrine Farmacia |
| Resumo: | 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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