Multitarget drugs as potential therapeutic agents for alzheimer’s disease. A new family of 5-substituted indazole derivatives as cholinergic and BACE1 inhibitors
Multitarget drugs are a promising therapeutic approach against Alzheimer’s disease. In this work, a new family of 5-substituted indazole derivatives with a multitarget profile including cholinesterase and BACE1 inhibition is described. Thus, the synthesis and evaluation of a new class of 5-substitut...
| Autores: | , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/279417 |
| Acceso en línea: | http://hdl.handle.net/10261/279417 |
| Access Level: | acceso abierto |
| Palabra clave: | Alzheimer’s disease BACE1 inhibitor BuChE inhibitor Indazole Multitarget drug |
| Sumario: | Multitarget drugs are a promising therapeutic approach against Alzheimer’s disease. In this work, a new family of 5-substituted indazole derivatives with a multitarget profile including cholinesterase and BACE1 inhibition is described. Thus, the synthesis and evaluation of a new class of 5-substituted indazoles has been performed. Pharmacological evaluation includes in vitro inhibitory assays on AChE/BuChE and BACE1 enzymes. Also, the corresponding competition studies on BuChE were carried out. Additionally, antioxi- dant properties have been calculated from ORAC assays. Furthermore, studies of anti-inflammatory proper- ties on Raw 264.7 cells and neuroprotective effects in human neuroblastoma SH-SY5Y cells have been performed. The results of pharmacological tests have shown that some of these 5-substituted indazole derivatives 1–4 and 6 behave as AChE/BuChE and BACE1 inhibitors, simultaneously. In addition, some indazole derivatives showed anti-inflammatory (3, 6) and neuroprotective (1–4 and 6) effects against Ab- induced cell death in human neuroblastoma SH-SY5Y cells with antioxidant properties. |
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