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New melatonin- N, N -dibenzyl(N -methyl)amine hybrids: Potent neurogenic agents with antioxidant, cholinergic, and neuroprotective properties as innovative drugs for alzheimers disease

AuthorsLópez-Iglesias, Beatriz ; Pérez, Concepción; Morales-García, José A. ; Alonso-Gil, Sandra ; Pérez Castillo, Ana ; López, Manuela G.; Conde, Santiago ; Rodríguez-Franco, María Isabel
Issue Date2014
PublisherAmerican Chemical Society
CitationJournal of Medicinal Chemistry 57(9): 3773-3785 (2014)
AbstractHere, we describe a new family of melatonin-N,N-dibenzyl(N-methyl)amine hybrids that show a balanced multifunctional profile covering neurogenic, antioxidant, cholinergic, and neuroprotective properties at low-micromolar concentrations. They promote maturation of neural stem cells into a neuronal phenotype and thus they could contribute to CNS repair. They also protect neural cells against mitochondrial oxidative stress, show antioxidant properties, and inhibit human acetylcholinesterase (AChE). Moreover, they displace propidium from the peripheral anionic site of AChE, preventing the β-amyloid aggregation promoted by AChE. In addition, they show low cell toxicity and can penetrate into the CNS. This multifunctional profile highlights these melatonin-N,N-dibenzyl(N-methyl)amine hybrids as useful prototypes in the research of innovative drugs for Alzheimers disease. © 2014 American Chemical Society.
Descriptionet al.
Identifiersdoi: 10.1021/jm5000613
issn: 0022-2623
e-issn: 1520-4804
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