†Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, 28006-Madrid, Spain.
‡Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas (IIB-CSIC), C/Arturo Duperier 4, 28029-Madrid, Spain.
ACS Chem Neurosci. 2015 May 20;6(5):800-10. doi: 10.1021/acschemneuro.5b00041. Epub 2015 Apr 9.
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.
6-甲氧基-1,2,3,4-四氢-β-咔啉（针叶啉）和 N-乙酰-5-甲氧基色胺（褪黑素）在结构上均与 5-羟色胺（血清素）有关。在这里，我们描述了一系列褪黑素刚性类似物的设计、合成和表征，这些类似物是由针叶啉和褪黑素结构杂交而成的。褪黑素-针叶啉杂合体的药理学评价包括血清素能和褪黑素能受体、代谢酶（单胺氧化酶）、抗氧化潜力、体外血脑屏障通透性和神经发生研究。在体外分离的成年大鼠侧脑室下区神经干细胞模型中，痕量浓度的针叶啉和 2-乙酰-6-甲氧基-1,2,3,4-四氢-β-咔啉（2）能够刺激早期神经发生和神经元成熟。这些作用可能分别通过血清素能和褪黑素能刺激来介导。
