Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (10): 2673-2679.DOI: 10.6023/cjoc201804016 Previous Articles     Next Articles



栗娜a,b, 辛景超a,b, 孟娅琪a,b, 李二冬a,b, 马启胜a,b, 包崇男a,b, 杨鹏a,b, 宋攀攀a,b, 崔飞a,b, 赵培荣b, 李雯a,b, 可钰a,b, 张秋荣a,b, 刘宏民a,b   

  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
  • 收稿日期:2018-04-10 修回日期:2018-05-04 发布日期:2018-06-06
  • 通讯作者: 可钰,;张秋荣,;刘宏民,;;
  • 基金资助:


Synthesis and Antitumor Evaluation of 2,4-Substituted Quinazoline Derivatives Containing Benzimidazole

Li Naa,b, Xin Jingchaoa,b, Meng Yaqia,b, Li Erdonga,b, Ma Qishenga,b, Bao Chongnana,b, Yang Penga,b, Song Panpana,b, Cui Feia,b, Zhao Peirongb, Li Wena,b, Ke Yua,b, Zhang Qiuronga,b, Liu Hongmina,b   

  1. a School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001;
    b Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001
  • Received:2018-04-10 Revised:2018-05-04 Published:2018-06-06
  • Contact: 10.6023/cjoc2018004016;;
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 81430085), the Natural Science Foundation of Henan Province (No. 182300410321) and the Technology Department Project of Henan Province (No. 182102310249).

In order to find more efficient and economical antitumor drugs, a series of novel 2,4-substituted quinazoline derivatives containing benzimidazole were designed, synthesized and evaluated for their antitumor activities on two human tumor cell lines including human gastric cancer cells (MGC-803), human breast cancer cells (MCF-7) and the normal human gastric epithelial cell line (GES-1) by using thiazolyl blue tetrazolium bromide (MTT) assay in vitro. Among all the tested compounds, some compounds displayed moderate to potent antitumor activities against MGC-803 and MCF-7. When the 4-position of quinazoline was substituted by different aromatic amines, 2-(((1H-benzo[d]imidazol-2-yl)methyl)thio)-N-(4-methoxyphen-yl)quinazolin-4-amine (15e) had good anti-tumor activity against MGC-803 with IC50 value of 4.60 μmol·L-1. When the 4-position of quinazoline was replaced by different chalcone, (E)-1-(4-((2-(((1H-benzo[d]imidazol-2-yl)methyl)thio)quinazo-lin-4-yl)amino)phenyl)-3-(3-nitrophenyl)prop-2-en-1-one (15k) had a strong anti-tumor activity against MGC-803 with IC50 value of 0.97 μmol·L-1, which was significantly better than compound 15e. However, the toxicity of compound 15e was more serious than compound 15k whose toxicity was similar to that of the control drug 5-fluorouracil and gefitinib against GES-1. The result of docking with epidermal growth factor receptor (EGFR) suggested that the binding mode of 15k was better than that of 15e. It is believed that this work would be very useful for developing a new series of EGFR inhibitors.

Key words: quinazoline, benzimidazole, synthesis, antitumor activities