Facultad de Ciencias Experimentales, Universidad Francisco de Vitoria, Pozuelo de Alarcón, 28223 Madrid, Spain.
Laboratory of Immune-Regulation, Gregorio Marañón Health Research Institute (IISGM), 28009 Madrid, Spain.
Molecules. 2023 Jun 20;28(12):4882. doi: 10.3390/molecules28124882.
Neuroinflammation plays a crucial role in the progression of Alzheimer's disease and other neurodegenerative disorders. Overactivated microglia cause neurotoxicity and prolong the inflammatory response in many neuropathologies. In this study, we have synthesised a series of isatin derivatives to evaluate their anti-neuroinflammatory potential using lipopolysaccharide activated microglia as a cell model. We explored four different substitutions of the isatin moiety by testing their anti-neuroinflammatory activity on BV2 microglia cells. Based on the low cytotoxicity and the activity in reducing the release of nitric oxide, pro-inflammatory interleukin 6 and tumour necrosis factor α by microglial cells, the -alkylated compound and the chlorinated showed the best results at 25 µM. Taken together, the data suggest that and are promising lead compounds for developing new neuroprotective agents.
神经炎症在阿尔茨海默病和其他神经退行性疾病的进展中起着关键作用。过度激活的小胶质细胞在许多神经病理学中引起神经毒性并延长炎症反应。在这项研究中，我们合成了一系列色氨酸衍生物，并用脂多糖激活的小胶质细胞作为细胞模型来评估它们的抗炎潜力。我们通过测试色氨酸部分的四个不同取代基在 BV2 小胶质细胞上的抗炎活性来探索它们。基于低细胞毒性和降低一氧化氮、促炎白细胞介素 6 和肿瘤坏死因子α释放的活性，-烷基化化合物 和氯化物 在 25µM 时表现出最佳效果。总的来说，这些数据表明 和 是开发新型神经保护剂的有前途的先导化合物。
