新型吲哚类衍生物的合成及体外免疫抑制活性的初步研究

Synthesis and evaluation of novel indole derivatives as potential immunosuppressive drugs

目的:以土槿乙酸结构特征为模板,吲哚为母核合成类土槿乙酸化合物,以期得到有更高免疫抑制活性的吲哚类衍生物。方法:对5-醛基吲哚和5-羧基吲哚的1,3,5位进行改造。1位进行烷基化改造,3位通过维尔斯迈尔-哈克反应与醛胺缩合反应进行延长,5位通过克脑文格尔反应与缩合酰化反应进行延长,得到吲哚类衍生物。经氢谱和高分辨质谱对其进行结构表征。采用噻唑蓝(MTT)法检测目标化合物对小鼠T、B淋巴细胞增殖的抑制作用。结果:合成得到两个系列共7个化合物,所有的化合物都经过HR-ESI-MS和1H-NMR验证,其中化合物5c对T细胞和B细胞有一定的增殖抑制活性,化合物9a,9b对B细胞有一定增殖抑制活性。结论:通过模拟土槿乙酸的两个长链结构合成了新的吲哚的类似物,发现了具有一定的免疫抑制活性的先导化合物。

Objective： To obtain indole derivatives with higher immunosuppressive activity, by synthesizing indole derivatives. Methods：Structural modifications of indole-5-carbox- aldehyde and 5-carboxy-indole were obtained through alkylation on N-1, Vilsmeier-Haack reaction and aldehyde-amine condensation on C-3, Knoevenagel reaction and acylated condensation on C-5. All the compounds were characterized by1H-NMR and HR-MS. Meanwhile, MTT assay was used to test their inhibiting activities on murine T and B cells. Results：Seven compounds of the two series were obtained; all of them were confirmed by HR-ESI-MS and1H-NMR validation. Compound 5c showed a certain degree of inhibiting activity against T cells and B cells. Compounds 9a and 9b showed a certain degree of inhibitory activity against B cells. Conclusion： By simulating the structures of two long chains of pseudolaric acid B, new indole analogues are synthesized and some of them may show a certain degree of immunosuppressive activity.