新型阿魏酸类衍生物的设计、合成及对LPS诱导N9小胶质细胞激活的抑制作用研究

目的设计合成一系列阿魏酸衍生物并测定其体外抑制LPS激活N9小胶质细胞的活性。方法以香兰素为起始原料,经Knoevenagel反应,与美金刚胺盐酸盐直接缩合得基本母核结构(AMJ),再经Mannich反应得到8个目标化合物。采用建立体外LPS激活N9小胶质细胞异常活化的筛选模型对合成的目标化合物活性进行评价。结果合成了8个未见报道的新化合物,其结构经MS及1H-NMR谱确证。活性实验结果表明,化合物4a⁴g能够显著抑制LPS刺激的N9小胶质细胞NO释放,在其发挥抑制作用的浓度范围内不影响小胶质细胞存活率。结论阿魏酸衍生物可能具有减轻小胶质细胞活化介导的神经系统疾病(如神经退行性疾病)的潜在作用。

Design,synthesis and LPS induced N9 microglia cell activation inhibitory effects of novel ferulic acid derivatives

Neurodegenerative diseases including Alzheimer＇s disease seriously affect the health and life quali- ty,which are becoming a social problem. The pathogenesis of neurodegenerative diseases is not clear and there is no effective method to cure them. So it is of great significance to develop more effective and safe agents for Alzheimer＇s disease. Some ferulic acid derivatives were designed and prepared via Knoevenagel reaction, condensation with memantine hydrochloride and Mannich reaction with vanillin as starting material. The structures of the target compounds were confirmed by MS and ^1H-NMR. The effects of target com- pounds on the NO production in vitro using LPS-activated N9 microglial cells were evaluated. And the results showed that 4a -4g significantly suppressed NO production induced by LPS in N9 microglial cells in a concentration-dependent manner. In summary, these data suggested that ferulic acid derivatives showed possible implication on neuroinflammation-mediated neurological disorders.