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New neurogenic lipoic-based hybrids as innovative Alzheimer's drugs with σ-1 agonism and β-secretase inhibition

AutorEstrada, Martín ; Pérez, Concepción; Soriano, Elena ; Pricl, Sabrina; Morales-García, José A. ; Pérez Castillo, Ana ; Rodríguez-Franco, María Isabel
Palabras claveLipoic 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 (AD)
Fecha de publicaciónjul-2016
EditorFuture Science
CitaciónFuture 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.
Descripciónet al.
Versión del editorhttps://doi.org/10.4155/fmc-2016-0036
URIhttp://hdl.handle.net/10261/143527
DOI10.4155/fmc-2016-0036
Identificadoresissn: 1756-8919
e-issn: 1756-8927
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