title: Neurogenic Potential Assessment and Pharmacological Characterization of 6-Methoxy-1,2,3,4-tetrahydro-β-carboline (Pinoline) and Melatonin-Pinoline Hybrids.
abstract: 6-Methoxy-1,2,3,4-tetrahydro-β-carboline (pinoline) and N-acetyl-5-methoxytryptamine (melatonin) are both structurally related to 5-hydroxytryptamine (serotonin). Here we describe the design, synthesis, and characterization of a series of melatonin rigid analogues resulting from the hybridization of both pinoline and melatonin structures. The pharmacological evaluation of melatonin-pinoline hybrids comprises serotonergic and melatonergic receptors, metabolic enzymes (monoamine oxidases), antioxidant potential, the in vitro blood-brain barrier permeability, and neurogenic studies. Pinoline at trace concentrations and 2-acetyl-6-methoxy-1,2,3,4-tetrahydro-β-carboline (2) were able to stimulate early neurogenesis and neuronal maturation in an in vitro model of neural stem cells isolated from the adult rat subventricular zone. Such effects are presumably mediated via serotonergic and melatonergic stimulation, respectively.
authors: †Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, 28006-Madrid, Spain.
authors: Mario
authors: M
authors: de la Fuente Revenga
authors: †Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, 28006-Madrid, Spain.
authors: Concepción
authors: C
authors: Pérez
authors: ‡Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas (IIB-CSIC), C/Arturo Duperier 4, 28029-Madrid, Spain.|§Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), C/Valderrebollo 5, 28031-Madrid, Spain.
authors: José A
authors: JA
authors: Morales-García
authors: ‡Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas (IIB-CSIC), C/Arturo Duperier 4, 28029-Madrid, Spain.|§Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), C/Valderrebollo 5, 28031-Madrid, Spain.
authors: Sandra
authors: S
authors: Alonso-Gil
authors: ‡Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas (IIB-CSIC), C/Arturo Duperier 4, 28029-Madrid, Spain.|§Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), C/Valderrebollo 5, 28031-Madrid, Spain.
authors: Ana
authors: A
authors: Pérez-Castillo
authors: ∥Institut de Recherches Servier, 125 Chemin de Ronde, 78290-Croissy sur Seine, France.
authors: Daniel-Henri
authors: DH
authors: Caignard
authors: ⊥Facultad de Farmacia, Departamento de Farmacología, Universidad de Santiago de Compostela, Campus Vida, La Coruña, 15782-Santiago de Compostela, Spain.
authors: Matilde
authors: M
authors: Yáñez
authors: #Facultad de Ciencias Químicas, Departamento de Química Orgánica I, Universidad Complutense de Madrid, 28040-Madrid, Spain.
authors: Ana M
authors: AM
authors: Gamo
authors: †Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, 28006-Madrid, Spain.
authors: María Isabel
authors: MI
authors: Rodríguez-Franco
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008550:Melatonin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D002243:Carbolines; C002272:6-methoxytryptoline; D008550:Melatonin
keywords: Melatonin; antioxidants; melatonergic receptors; monoamine oxidases; neurogenesis; pinoline; serotonergic receptors