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 <b>QT78</b> in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer’s disease therapy. We have found that <b>QT78</b> is less toxic than tacri...
| Autores: | , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/180729 |
| Acceso en línea: | http://hdl.handle.net/10261/180729 |
| Access Level: | acceso abierto |
| Palabra clave: | Alzheimer’s disease Cholinesterase inhibitors Hepatotoxicity Molecular modeling Neuroprotection Quinoxalines Quinoxalinetacrines Tacrine |
| Sumario: | We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid <b>QT78</b> in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer’s disease therapy. We have found that <b>QT78</b> is less toxic than tacrine at high concentrations (from 100 μM to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC<sub>50</sub> (hAChE) = 22.0 ± 1.3 μM; IC<sub>50</sub> (hBuChE) = 6.79 ± 0.33 μM). Moreover, <b>QT78</b> showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer’s disease. |
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