Neurogenic Potential Assessment and Pharmacological Characterization of 6-Methoxy-1,2,3,4-tetrahydro-beta-carboline (Pinoline) and Melatonin-Pinoline Hybrids

作者：de la Fuente Revenga Mario; Perez Concepcion; Morales Garcia Jose A; Alonso Gil Sandra; Perez Castillo Ana; Caignard Daniel Henri; Yanez Matilde; Gamo Ana M; Isabel Rodriguez Franco Maria

来源：ACS Chemical Neuroscience, 2015, 6(5): 800-810.

DOI：10.1021/acschemneuro.5b00041

• Melatonin
• pinoline
• neurogenesis
• serotonergic receptors
• melatonergic receptors
• monoamine oxidases
• antioxidants

6-Methoxy-1,2,3,4-tetrahydro-beta-carboline (pi-noline) 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-beta-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.

• 出版日期2015-5