有机化学 ›› 2020, Vol. 40 ›› Issue (4): 978-987.DOI: 10.6023/cjoc201909016 上一篇    下一篇

研究论文

新型三甲氧基苯基喹啉衍生物的设计、合成及抗肿瘤活性研究

吴博文a,c, 崔鑫鑫a,c, 朱挺a,c, 王胜辉b, 陆超凡b, 王金杰a,c, 党贺祥a,c, 张赛扬a,b,d, 丁丽娜a,c, 金成允a,c   

  1. a 新药创制与药物安全性评价河南省协同创新中心 郑州 450001;
    b 郑州大学基础医学院 郑州 450001;
    c 教育部药物制备关键技术重点实验室 郑州 450001;
    d 郑州大学河南省先进技术研究院 郑州 450001
  • 收稿日期:2019-09-10 修回日期:2019-11-21 发布日期:2020-05-06
  • 通讯作者: 张赛扬, 丁丽娜, 金成允 E-mail:saiyangz@zzu.edu.cn;dinglina123@126.com;cyjin@zzu.edu.cn
  • 基金资助:
    国家自然科学基金(Nos.81703541,81673322)和中国博士后科学基金(No.2018M632812)资助项目.

Design, Synthesis and Anticancer Activity Studies of Novel Trimethoxyphenyl-quinoline Derivatives

Wu Bowena,c, Cui Xinxina,c, Zhu Tinga,c, Wang Shenghuib, Lu Chaofanb, Wang Jinjiea,c, Dang Hexianga,c, Zhang Saiyanga,b,d, Ding Li'naa,c, Jin Chengyuna,c   

  1. a Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou 450001;
    b School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001;
    c Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001;
    c Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450001
  • Received:2019-09-10 Revised:2019-11-21 Published:2020-05-06
  • Supported by:
    Project supported by the National Natural Science Foundation of China (Nos. 81703541, 81673322) and the China Postdoctoral Science Foundation (No. 2018M632812).

为了寻找新型高效抗肿瘤候选药物,设计并合成了一系列新型三甲氧基苯基-喹啉杂合体,并评估了目标化合物对三种不同肿瘤细胞EC-109(人食管癌细胞),PC-3(人前列腺癌细胞)和MGC-803(人胃癌细胞)的抗增殖活性.结果表明N-(3-(氯甲基)苄基)-3,4,5-三甲氧基-N-(喹啉-8-基)苯甲酰胺(12j)对PC-3细胞具有良好的抗增殖活性,IC50值为9.23 μmol/L.同时,化合物12j抑制PC-3细胞增殖和克隆形成.进一步机制研究表明,化合物12j可以将PC-3细胞阻滞在G2/M期,并通过激活内源性和外源性凋亡途径诱导细胞凋亡.

关键词: 喹啉, 三甲氧基苯基, 抗肿瘤活性, 细胞周期阻滞, 凋亡

With the expectation to find out novel and effective anti-tumor agents, a series of novel trimethoxyphenyl-quinoline hybrids were designed, synthesized and evaluated for antiproliferative activity against three human cancer cell lines (EC-109, human esophageal cancer cells; PC-3, human prostate cancer cells; MGC-803, human gastric cancer cells). N-(3-(Chloromethyl)benzyl)-3,4,5-trimethoxy-N-(quinolin-8-yl)benzamide (12j) showed the most potent antitumor activity against PC-3 cells with IC50 value of 9.23 μmol/L. Meanwhile, compound 12j inhibited the cell viability and colony formation of PC-3 cells. Further mechanism studies revealed that compound 12j could arrest PC-3 cells in G2/M phase and induce cell apoptosis via activating intrinsic and extrinsic apoptosis pathway.

Key words: quinoline, trimethoxyphenyl, anticancer, cell cycle arrest, apoptosis