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Título: | New neurogenic lipoic-based hybrids as innovative Alzheimer's drugs with σ-1 agonism and β-secretase inhibition |
Autor: | Estrada, Martín CSIC ORCID CVN; Pérez, Concepción CSIC ORCID; Soriano, Elena CSIC; Pricl, Sabrina; Morales-García, José A. CSIC ORCID; Pérez Castillo, Ana CSIC ORCID; Rodríguez-Franco, María Isabel CSIC ORCID | Palabras clave: | Lipoic acid Acetylcholinesterase (AChE) Beta-secretase-1 (BACE1) sigma-1 receptor (σ1R) Neurogenic properties N,N-dibenzyl(N-methyl)amine N-benzylpiperidine Multi-target directed ligands (MTDLs) Alzheimer’s disease |
Fecha de publicación: | jul-2016 | Editor: | Future Science | Citación: | Future Medicinal Chemistry 8(11): 1191-1207 (2016) | Resumen: | [Background]: Neurogenic agents emerge as innovative drugs for the treatment of Alzheimer's disease (AD), whose pathological complexity suggests strengthening research in the multi-target directed ligands strategy. [Results]: By combining the lipoic acid structure with N-benzylpiperidine or N,N-dibenzyl(N-methyl)amine fragments, new multi-target directed ligands were obtained that act at three relevant targets in AD: σ-1 receptor (σR), β-secretase-1 (BACE1) and acetylcholinesterase (AChE). Moreover, they show potent neurogenic properties, good antioxidant capacity and favorable CNS permeability. Molecular modeling studies on AChE, σR and BACE1 highlight relevant drug-protein interactions that may contribute to the development of new disease-modifying drugs. [Conclusion]: New lipoic-based σ agonists endowed with neurogenic, antioxidant, cholinergic and amyloid β-peptide-reducing properties have been discovered for the potential treatment of AD. | Descripción: | et al. | Versión del editor: | https://doi.org/10.4155/fmc-2016-0036 | URI: | http://hdl.handle.net/10261/143527 | DOI: | 10.4155/fmc-2016-0036 | Identificadores: | issn: 1756-8919 e-issn: 1756-8927 |
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