有机化学 ›› 2020, Vol. 40 ›› Issue (9): 2804-2810.DOI: 10.6023/cjoc202005081 上一篇    下一篇

研究论文

含丙烯酰胺结构的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, 李二冬a,b, 刘丽敏a,b, 刘秀娟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 45000;
    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:2020-05-28 修回日期:2020-06-17 发布日期:2020-07-01
  • 通讯作者: 张秋荣, 单丽红, 刘宏民 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)、省部共建食管癌防治国家重点实验室开放基金(No.K2020000X)资助项目.

Synthesis and Antitumor Activity of Novel Quinazoline Derivatives Containing Acrylamide

Zhang Luyea,b, Zhang Yanga,b, Wang Zhengjiea,b, Wang Taoa,b, Li Erdonga,b, Liu Limina,b, Liu Xiujuana,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 of Henan Province, Zhengzhou 450001;
    c State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou 450052;
    d Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001
  • Received:2020-05-28 Revised:2020-06-17 Published:2020-07-01
  • Supported by:
    Project supported by the National Natural Science Foundation of China (No. U1904163), and the Opening Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment (No. K2020000X).

为了寻找高效低毒的抗肿瘤药物,设计并合成了一系列新型的含N-(3-丙烯酰胺苯基)乙酰胺结构的喹唑啉类衍生物,并采用噻唑蓝(MTT)法测定了目标化合物对H1975(人肺腺癌细胞系),PC-3(人前列腺癌细胞系),MGC-803(人胃癌细胞系)三种肿瘤细胞的抗增殖活性.结果显示大部分化合物具有较好的抗肿瘤活性,其中N-(3-(2-(((4-((4-氯苯基)氨基)-7-甲氧基喹唑啉-6-基)氧基)乙酰氨基)苯基)丙烯酰胺(13j)对H1975,MGC-803两种细胞显示出最好的抗增殖活性,IC50值分别为(6.77±0.65)和(4.06±0.34)μmol/L,其活性均优于阳性对照品吉非替尼,为抗肿瘤药物的研究提供了线索.

关键词: 丙烯酰胺, 喹唑啉, 合成, 抗肿瘤活性

In order to find efficient and low toxicity anti-tumor drugs, a series of novel quinazoline derivatives containing N-(3-aminophenyl)acrylamide were synthesized and their antiproliferative activities were evaluated against three human cancer cell lines (H1975, PC-3, MGC-803) by using methyl thiazolyl tetrazolium (MTT) assay. The results showed that most compounds exhibited better antiproliferative activities against the four human tumor cell lines. Among them, N-(3-(2-((4-((4-chlorophenyl)amino)-7-methoxy-quinazolin-6-yl)oxy)acetamido)phenyl)acrylamide (13j) showed the best antiproliferative activity against H1975 and MGC-803 cancer cell lines with IC50 values of (6.77±0.65) and (4.06±0.34) μmol/L, respectively. Its activity was better than the positive control gefitinib. In a nutshell, this work provides clues to discover antitumor agent based on the quinazoline scaffold.

Key words: acrylamide, quinazoline, synthesis, antiproliferative activity