3,3′-双取代-2-吲哚酮的合成及其抗肿瘤活性研究-陕西师范大学学报期刊社网站

陕西师范大学学报（自然科学版）

生命科学

3,3′-双取代-2-吲哚酮的合成及其抗肿瘤活性研究

李午戊1,2，张尊听1*

(1 教育部药用资源与天然药物化学重点实验室，西北濒危药材资源开发国家工程实验室，陕西师范大学化学化工学院，陕西西安 710119； 2 咸阳师范学院化学与化工学院，陕西咸阳 712000)

张尊听，男，教授，博士生导师。 E-mail: zhangzt@snnu.edu.cn

摘要:

以靛红(2,3-二酮二氢吲哚)及其衍生物作为先导化合物，利用活性结构单元拼接原理，通过Morita-Baylis-Hillman反应将3,3′-双取代-2-吲哚酮结构单元与丙烯酸酯基团构筑在同一分子中，合成系列3,3′-双取代-2-吲哚酮(3a—3r)，结构经1H NMR、13C NMR和HRMS或MS表征。化合物3a—3r对于人白血病细胞(K562)和前列腺癌细胞(PC-3)的体外抗增值活性采用MTT法进行测定。药理活性研究表明，该类化合物对于K562和PC-3均有抗增殖活性，其中3j对K562的抗增殖活性最强，3r对PC-3的抗增殖活性最强，这两者的抗增殖活性分别为阳性对照物顺铂的2.85倍和4.24倍。

关键词：

3,3′-双取代-2-吲哚酮；合成；抗肿瘤活性

收稿日期：

2016-05-23

中图分类号：

R914

文献标识码：

文章编号：

1672-4291(2017)01-0064-07doi:10.15983/j.cnki.jsnu.2017.01.314

基金项目：

国家自然科学基金(21372150); 陕西省自然科学基础研究计划(2014JQ2073); 中央高校基本科研业务费专项资金(GK261001095).

Doi:

Synthesis and antitumor activity of 3, 3′-bisubstituted-2-oxindole derivatives

LI Wuwu1,2, ZHANG Zunting1*

(1 Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi′an 710119, Shaanxi, China;2 College of Chemistry & Chemical Engineering, Xianyang Normal University, Xianyang 712000, Shaanxi, China)

Abstract:

According to physiological activity structure combination strategy, 3, 3′-bisubstituted-2-oxindole skeleton and acrylate group were joined together, through the Morita-Baylis-Hilleman reaction. A series of 3, 3′-bisubstituted-2-oxindole derivatives(3a—3r) were synthesized with isatin (2,3-diketoindoline) and its derivatives as leading compounds. The structure of 3a—3r were characterized by 1H NMR, 13C NMR and MS or HRMS. Their anti-proliferative activities in vitro against human leukemia cells K562 and human prostate cancer cells PC-3 were evaluated by the standard MTT assay. The pharmacological activity results showed that this kind of compounds has anti-proliferative activity against human cancer cells K562 and PC-3, the anti-proliferative activity against K562 of 3j is the strongest, the anti-proliferative activity against Pc-3 of 3r is the strongest, their anti-proliferative activity are 2.85 and 4.24 times better than that in positive control group cisplatin, respectively.

KeyWords:

3, 3′-bisubstituted-2-oxindole; synthesis; antitumor activity