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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

22卷

期数:

2016年03期

页码:

195

栏目:

基础医学

出版日期:

2016-05-20

文章信息/Info

Title:

Synthesis and evaluation of novel Indole derivatives as potential Immunosuppressive drugs

文章编号:

1006-8147（2016）03-0195-04

作者:

赵阳¹; 王冀腾²; 李楠¹; 2; 陈诗雅²; 李覃²; 陈虹¹; 2; 刘艳霞¹

(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)

Author(s):

ZHAO Yang¹; WANG Yi -teng²; LI Nan¹; 2; LI Tan²; CHEN Hong¹; 2; LIU Yan -xia¹

(1. School of Pharmacy, Tianjin Medical University, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, Tianjin 300070, China; 2. Department of Pharmacognosy, Logistic University of PAP, Tianjin 300309, China)

关键词:

5-醛基吲哚' target="_blank" rel="external">"> 5-醛基吲哚; 5-羧基吲哚; 土槿乙酸; 免疫抑制活性

Keywords:

Indole-5-carboxaldehyde;  5-carboxy-indole;  pseudolaric acid B;  immuno- suprressive activity

分类号:

R9

DOI:

-

文献标志码:

A

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。

Abstract:

Objective: To obtain indole derivatives with higher immunosuppressive activity, by synthesizing Indole deviratives. Methods: Structural modifications of Indole-5-carbox- aldehyde and 5-carboxy-indole were obtained through alkylationon 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 by ¹H-NMR and HR-MS. Meanwhile, MTT assay was used to test their inhibiting activities on murine T and B cells. Results: Seven compounds in the two series were obtained; all of them were confirmed by HR-ESI-MS and ¹H-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, we could synthesize new indole analogues and some of them may show a certain degree of immunosuppressive activity.

参考文献/References:

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备注/Memo

备注/Memo:

基金项目 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）

作者简介 赵阳（1993-），男，硕士在读，研究方向：天然产物结构改造；通信作者：刘艳霞，E-mail: liu_yanxia126@126.com。

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更新日期/Last Update: 2016-05-24