Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (7): 1967-1974.DOI: 10.6023/cjoc201902036 Previous Articles     Next Articles

Special Issue: 陈茹玉先生诞辰100周年

含苯并噻唑的4-氨基喹唑啉衍生物的合成及抗肿瘤活性研究

张路野a,b, 张洋a,b, 汪正捷a,b, 王涛a,b, 刘丽敏a,b, 刘秀娟a,b, 李二冬a,b, 宋攀攀a,b, 郑甲信a,b, 可钰a,b, 单丽红a,d, 刘宏民a,b,c,d, 张秋荣a,b,d   

  1. a 郑州大学药学院 郑州 450001;
    b 新药创制与药物安全性评价河南省协同创新中心 郑州 450001;
    c 省部共建食管癌防治国家重点实验室 郑州 450052;
    d 教育部药物制备关键技术重点实验室 郑州 450001
  • 收稿日期:2020-02-26 修回日期:2020-04-13 发布日期:2019-05-06
  • 通讯作者: 单丽红, 刘宏民, 张秋荣 E-mail:zqr409@yeah.net;shlh@zzu.edu.cn;liuhm@zzu.edu.cn
  • 基金资助:
    国家自然科学基金(No.U1904163)、蛋白关键研究(No.2018YFE0195100)和省部共建食管癌防治国家重点实验室资助的开放基金(No.K2020000X)资助项目.

Synthesis and Antitumor Activity of Novel 4-Aminoquinazoline Derivatives Containing Benzothiazole

Zhang Luyea,b, Zhang Yanga,b, Wang Zhengjiea,b, Wang Taoa,b, Liu Limina,b, Liu Xiujuana,b, Li Erdonga,b, Song Panpana,b, Zheng Jiaxina,b, Ke Yua,b, Shan Lihonga,d, Liu Hongmina,b,c,d, Zhang Qiuronga,b,d   

  1. a School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001;
    b Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001;
    c State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052;
    d Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001
  • Received:2020-02-26 Revised:2020-04-13 Published:2019-05-06
  • Supported by:
    Project supported by the National Natural Science Foundation of China (No. U1904163) and the Key Research Program of Proteins (No. 2018YFE0195100) and the Openning Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment (No. K2020000X).

In order to find efficient and low toxicity anti-tumor drugs, a series of novel 4-aminoquinazoline derivatives containing benzothiazole were designed and synthesized. And their antiproliferative activities against four human cancer cell lines[human breast cancer cell line (MCF-7), human gastric carcinoma cell line (MGC-803), human prostate cancer cell line (PC-3), human gastric carcinoma cell line (HGC-27)] were evaluated by using methyl thiazolyl tetrazolium (MTT) assay. The results showed that most compounds exhibited good antiproliferative activities against the four human tumor cell lines. Among them, 2-((benzo[d]thiazol-2-ylmethyl)thio)-N-(3-chloro-4-fluorophenyl)-quinazolin-4-amine (13n) showed the best antiproliferative activity against MCF-7, MGC 803, PC-3 and HGC-27 cancer cell lines, with IC50 values of (6.01±0.54), (7.63±0.48), (6.16±0.34), (7.59±0.62) μmol·L-1, respectively. Its activity was better than the positive control gefitinib. Molecular docking showed that compound 13n could bind well with epidermal growth factor receptor (EGFR). In a nutshell, this work provides clues to discover antitumor agent based on the quinazoline scaffold.

Key words: benzothiazole, 4-aminoquinazoline, synthesis, antiproliferative activity