Buendia Izaskun, Navarro Elisa, Michalska Patrycja, Gameiro Isabel, Egea Javier, Abril Sheila, López Alicia, González-Lafuente Laura, López Manuela G, León Rafael
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Instituto Teófilo Hernando, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
Future Med Chem. 2015;7(15):1961-9. doi: 10.4155/fmc.15.99. Epub 2015 Oct 23.
BACKGROUND: Neurodegenerative diseases share many pathological pathways, such as abnormal protein aggregation, mitochondrial dysfunction, extensive oxidative stress and neuroinflammation. Cells have an intrinsic mechanism of protection, the Nrf2 transcriptional factor, known as the master regulator of redox homeostasis. RESULTS: Based on the common features of these diseases we have designed a multi-target hybrid structure derived from melatonin and ethyl cinnamate. The obtained derivatives were Nrf2 inducers and potent-free radical scavengers. These new compounds showed a very interesting neuroprotective profile in several in vitro models of oxidative stress, Alzheimer's disease and brain ischemia. CONCLUSION: We have designed a new hybrid structure with complementary activities. We have identified compound 5h as an interesting Nrf2 inducer, very potent antioxidant and neuroprotectant.
背景：神经退行性疾病具有许多共同的病理途径，如异常蛋白质聚集、线粒体功能障碍、广泛的氧化应激和神经炎症。细胞具有一种内在的保护机制，即核因子E2相关因子2（Nrf2）转录因子，它被称为氧化还原稳态的主要调节因子。 结果：基于这些疾病的共同特征，我们设计了一种源自褪黑素和肉桂酸乙酯的多靶点杂合结构。所得到的衍生物是Nrf2诱导剂和有效的自由基清除剂。这些新化合物在氧化应激、阿尔茨海默病和脑缺血的几种体外模型中显示出非常有趣的神经保护作用。 结论：我们设计了一种具有互补活性的新型杂合结构。我们已确定化合物5h是一种有趣的Nrf2诱导剂、强效抗氧化剂和神经保护剂。
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