有机化学 ›› 2018, Vol. 38 ›› Issue (10): 2657-2665.DOI: 10.6023/cjoc201803051 上一篇    下一篇

研究论文

含1,3,4-噻二唑、硫醚、酰胺的1,3-二取代吲哚酮衍生物的设计、合成及抗肿瘤活性研究

田坤a, 孟娇b, 甘宜远b, 李小琴a, 巫受群a, 陈洁b, 李文b, 漆亚云b, 胡伟男b, 王贞超b,c, 欧阳贵平a,b,c   

  1. a 贵州大学精细化工研究开发中心 绿色农药与农业生物工程国家重点实验室培育基地 教育部绿色农药与生物工程重点实验室 贵阳 550025;
    b 贵州大学药学院 贵阳 550025;
    c 贵州省合成药物工程实验室 贵阳 550025
  • 收稿日期:2018-03-29 修回日期:2018-05-06 出版日期:2018-10-25 发布日期:2018-06-06
  • 通讯作者: 欧阳贵平,E-mail:oygp710@163.com;王贞超,E-mail:wzc.4884@163.com E-mail:oygp710@163.com;wzc.4884@163.com
  • 基金资助:

    贵州省科技计划(No.20161055)、贵州省教育厅青年科技人才成长(No.KY[2017]115)和药用植物功效与利用国家重点实验室(No.FAMP201707K)资助项目.

Design, Synthesis and Antitumor Activity Evaluation of 1,3,4-Thia-diazole, Thioether and Amide Based 1,3-Disubstituted-indol-2-one Derivatives

Tian Kuna, Meng Jiaob, Gan Yiyuanb, Li Xiaoqina, Wu Shouquna, Chen Jieb, Li Wenb, Qi Yayunb, Hu Weinanb, Wang Zhenchaob,c, Ouyang Guipinga,b,c   

  1. a State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research of Fine Chemicals, Guizhou University, Guiyang 550025;
    b College of Pharmacy, Guizhou University, Guiyang 550025;
    c Drug Synthetic Engineering Laboratory of Guizhou Province, Guiyang 550025
  • Received:2018-03-29 Revised:2018-05-06 Online:2018-10-25 Published:2018-06-06
  • Contact: 10.6023/cjoc201803051 E-mail:oygp710@163.com;wzc.4884@163.com
  • Supported by:

    Project supported by the Guizhou Science Technology Program (No. 20161055), the Young Talents Scientific Research Foundation of Guizhou Education Department (No. KY[2017]115), and the State Key Laboratory of Functions and Applications of Medicinal Plants (No. FAMP201707K).

以吲哚酮为先导化合物,设计合成了20个含1,3,4-噻二唑、硫醚、酰胺的1,3-二取代吲哚酮衍生物.采用噻唑蓝(MTT)试验法测试目标化合物的体外抑制肿瘤细胞生长活性,测试结果表明:部分目标化合物对人肝癌细胞HepG2、人转移胰腺癌细胞AsPc-1和人宫颈癌细胞Hela表现出良好的抑制活性;其中N-(5-((2-氟苄基)硫基)-1,3,4-噻二唑-2-基)-3-(2-氧代-3-((对-甲苯基)亚氨基)二氢吲哚-1-基)丙酰胺(6l)和N-(5-((2-甲基苄基)硫基)-1,3,4-噻二唑-2-基)-3-(2-氧代-3-((对甲苯基)亚氨基)二氢吲哚-1-基)丙酰胺(6p)对HePG2、AsPc-1和Hela细胞的IC50分别为(11.47±0.01)、(2.43±0.05)和(1.91±0.06)μmol/L;(14.32±0.01)、(1.61±0.04)和(2.77±0.05)μmol/L,其抑制活性均优于阳性对照吉非替尼[(16.41±0.05)、(5.19±0.02)和(7.89±0.05)μmol/L].

关键词: 吲哚酮衍生物, 噻二唑, 硫醚, 酰胺, 肿瘤抑制活性

A series of novel 1,3-disubstituted-indol-2-one derivatives containing 1,3,4-thiadiazole, thioether and amide moiety were designed and synthesized based on 2,3-dioxindole (isatin). The inhibition activities of all the target compounds against several cancer cell lines were evaluated via thiazolyl blue tetrazolium bromide (MTT) assay method. The preliminary bioassay results indicated that all of the title compounds exhibited a certain antitumor activity in vitro against human liver cancer cell line (HepG2), human transfer of pancreatic cancer cell line (AsPc-1) and human cervical cancer cell line (Hela). The IC50s values of N-(5-((2-fluorobenzyl)thio)-1,3,4-thiadiazol-2-yl)-3-(2-oxo-3-(p-tolylimino)indolin-1-yl)propanamide (6l) [(11.47±0.01), (2.43±0.05), (1.91±0.06) μmol/L, respectively] and N-(5-((2-methylbenzyl)thio)-1,3,4-thiadiazol-2-yl)-3-(2-oxo-3-(p-tolylimino)indolin-1-yl)-propanamide (6p) [(14.32±0.01), (1.61±0.04), (2.77±0.05) μmol/L, respectively] against HepG2, AsPc-1 and Hela cell lines were lower than that of control gefitinib [(16.41±0.05), (5.19±0.02), (7.89±0.05) μmol/L, respecti-vely].

Key words: indol-2-one derivatives, thiadiazole, thioether, amide, antitumor activity