Academias de Fisiología, Bioquímica Médica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón s/n, Col. Casco de Santo Tomás, Alc. Miguel Hidalgo, Mexico City 11340, Mexico.
Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón s/n, Col. Casco de Santo Tomás, Alc. Miguel Hidalgo, Mexico City 11340, Mexico.
Int J Mol Sci. 2022 Mar 17;23(6):3229. doi: 10.3390/ijms23063229.
Preclinical and clinical evidence supports melatonin and its analogues as potential treatment for diseases involving cognitive deficit such as Alzheimer's disease. In this work, we evaluated by in silico studies a set of boron-containing melatonin analogues on MT1 and MT2 receptors. Then, we synthesized a compound (borolatonin) identified as potent agonist. After chemical characterization, its evaluation in a rat model with cognitive deficit showed that it induced ameliorative effects such as those induced by equimolar administration of melatonin in behavioral tests and in neuronal immunohistochemistry assays. Our results suggest the observed effects are by means of action on the melatonin system. Further studies are required to clarify the mechanism(s) of action, as the beneficial effects on disturbed memory by gonadectomy in male rats are attractive.
临床前和临床证据支持褪黑素及其类似物作为治疗涉及认知缺陷的疾病（如阿尔茨海默病）的潜在药物。在这项工作中，我们通过计算机研究评估了一组含硼的褪黑素类似物对 MT1 和 MT2 受体的作用。然后，我们合成了一种被鉴定为有效激动剂的化合物（borolatonin）。经过化学表征，在具有认知缺陷的大鼠模型中的评估表明，它在行为测试和神经元免疫组织化学检测中诱导了类似于褪黑素等摩尔给药的改善作用。我们的结果表明，观察到的作用是通过褪黑素系统的作用来实现的。需要进一步的研究来阐明其作用机制，因为对去势雄性大鼠记忆障碍的有益作用很有吸引力。
