Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 57, Issue 9, Pages 3773-3785Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm5000613
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Funding
- Spanish Ministry of Economy and Competitiveness [SAF2012-31035, SAF2009-13015-C02-01, SAF2012-32223]
- Fundacion de Investigacion Medica Mutua Madrilena Automovilistica [AP103952012]
- CSIC [PIE-201280E074]
- CSIC
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Here, 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 beta-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 Alzheimer's disease.
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