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2022 , Vol. 42 >Issue 1: 249 - 256

DOI: https://doi.org/10.6023/cjoc202107026

研究论文

含三氟甲基的2,4,6-三取代喹唑啉衍生物的合成及抗肿瘤活性研究

  • 汪正捷 ,
  • 戴洪林 ,
  • 司晓杰 ,
  • 高潮 ,
  • 刘丽敏 ,
  • 张路野 ,
  • 张洋 ,
  • 宋亚丹 ,
  • 赵培荣 ,
  • 郑甲信 ,
  • 可钰 ,
  • 刘宏民 ,
  • 张秋荣
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  • a 郑州大学药学院 郑州 450001
    b 郑州大学 新药研究与安全评价协同创新中心 郑州 450001
    c 郑州大学 食管癌防治国家重点实验室 郑州 450052
    d 郑州大学 教育部药物制备关键技术重点实验室 郑州 450001

收稿日期: 2021-07-12

  修回日期: 2021-08-13

  网络出版日期: 2021-08-29

基金资助

国家自然科学基金(U1904163); 国家蛋白质研究项目(2018YFE0195100); 省部共建食管癌防治国家重点实验室资助的开放基金(K2020000X)

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Synthesis and Antitumor Activity of 2,4,6-Trisubstituted Novel Quinazoline Derivatives Containing Trifluoromethyl

  • Zhengjie Wang ,
  • Honglin Dai ,
  • Xiaojie Si ,
  • Chao Gao ,
  • Limin Liu ,
  • Luye Zhang ,
  • Yang Zhang ,
  • Yadan Song ,
  • Peirong Zhao ,
  • Jiaxin Zheng ,
  • Yu Ke ,
  • Hongmin Liu ,
  • Qiurong Zhang
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  • a School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
    b Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, 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 of China, Zhengzhou University, Zhengzhou 450001
* Corresponding authors. E-mail: ;
;

Received date: 2021-07-12

  Revised date: 2021-08-13

  Online published: 2021-08-29

Supported by

National Natural Science Foundation of China(U1904163); National Key Research Program of Proteins(2018YFE0195100); Opening Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment(K2020000X)

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摘要

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三氟甲基基团的2,4,6-三取代喹唑啉喹唑啉类衍生物, 并采用噻唑蓝(MTT)比色法测定目标化合物对人前列腺癌细胞系(PC-3)、人乳腺癌细胞系(MCF-7)、人食管癌细胞系(Eca-109)、人胃癌细胞系(MGC-803)、人未分化胃癌细胞系(HGC-27)、人非小细胞肺癌细胞系(A549)和人非小细胞肺癌细胞系(H1975)的抗肿瘤活性. 结果显示部分化合物表现出中度至强效的抗肿瘤活性, 其中N-(3-溴苯基)-6-甲氧基-2-((4-(三氟甲基)苄基)硫代)喹唑啉-4-胺(16l)对PC-3细胞具有最好的抗肿瘤活性, IC50值为(2.22±0.15) μmol/L, 抗肿瘤活性明显优于阳性对照品吉非替尼. 此外, 化合物16l对PC-3细胞以浓度依赖与时间依赖的方式诱导其凋亡.

关键词： 三氟甲基; 喹唑啉; 合成; 抗肿瘤活性

本文引用格式

汪正捷 , 戴洪林 , 司晓杰 , 高潮 , 刘丽敏 , 张路野 , 张洋 , 宋亚丹 , 赵培荣 , 郑甲信 , 可钰 , 刘宏民 , 张秋荣 . 含三氟甲基的2,4,6-三取代喹唑啉衍生物的合成及抗肿瘤活性研究[J]. 有机化学, 2022 , 42(1) : 249 -256 . DOI: 10.6023/cjoc202107026

Abstract

In order to find efficient and low toxicity antitumor drugs, a series of novel 2,4,6-trisubstituted quinazoline derivatives containing trifluoromethyl were synthesized and evaluated for their antitumor activities against human cancer cell lines (PC-3, MCF-7, Eca-109, MGC-803, HGC-27, A549, H1975) by using methyl thiazolyl tetrazolium (MTT) assay. Most of compounds exerted moderate to excellent antitumor activity against seven human cancer cells. Among them, N-(3-bromophenyl)-6-methoxy-2-((4-(trifluoromethyl)benzyl)thio)quinazolin-4-amine (16l) showed the best antitumor activity against PC-3 cancer cell line, with the IC50 values of (2.22±0.15) μmol/L, which was better than the positive control of gefitinib. At the same time, and compound 16l could dose-dependently and time-dependently induce PC-3 cells apoptosis.

Key words： trifluoromethyl; quinazoline; synthesis; antitumor activity

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