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

作　　者：赵阳[1] 王翼腾 李楠[1,2] 陈诗雅[2] 李覃[2] 陈虹[1,2] 刘艳霞[1] 

机构地区：[1]天津医科大学药学院天津市临床药物关键技术重点实验室,天津300070 [2]中国人民武装警察部队后勤学院生药与药剂学教研室,天津300309

出　　处：《天津医科大学学报》2016年第3期195-198,203,共5页Journal of Tianjin Medical University

基　　金：国家自然科学基金资助项目(30873363);天津市应用基础项目基金资助(08JCYBJC070000)

摘　　要：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.

关 键 词：5-醛基吲哚 5-羧基吲哚 土槿乙酸 免疫抑制活性 

分 类 号：R9[医药卫生—药学]