title: New melatonin-N,N-dibenzyl(N-methyl)amine hybrids: potent neurogenic agents with antioxidant, cholinergic, and neuroprotective properties as innovative drugs for Alzheimer's disease.
abstract: 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 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 Alzheimer's disease.
authors.affiliation: Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC) , C/Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: López-Iglesias
authors.forename: Concepción
authors.initials: C
authors.lastname: Pérez
authors.forename: José A
authors.initials: JA
authors.lastname: Morales-García
authors.forename: Sandra
authors.initials: S
authors.lastname: Alonso-Gil
authors.forename: Ana
authors.initials: A
authors.lastname: Pérez-Castillo
authors.forename: Alejandro
authors.initials: A
authors.lastname: Romero
authors.forename: Manuela G
authors.initials: MG
authors.lastname: López
authors.forename: Mercedes
authors.initials: M
authors.lastname: Villarroya
authors.forename: Santiago
authors.initials: S
authors.lastname: Conde
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Rodríguez-Franco
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001812:Blood-Brain Barrier; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008550:Melatonin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D008550:Melatonin