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Chinese Journal of Organic Chemistry >

2021 , Vol. 41 >Issue 1: 310 - 317

DOI: https://doi.org/10.6023/cjoc202007067

Article

Design, Synthesis and Antitumor Activity Evaluation Research of Novel 2,4,6-Substituted Pyrimidine Derivatives

  • Yang Zhang ,
  • Luye Zhang ,
  • Jikuan Wang ,
  • Limin Liu ,
  • Tao Wang ,
  • Na Li ,
  • Zhengjie Wang ,
  • Xiujuan Liu ,
  • Yaxin Chen ,
  • Danlin Zhao ,
  • Jiaxin Zheng ,
  • Lihong Shan ,
  • 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 450001
    c Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001
    d State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou 450052

Received date: 2020-07-29

  Revised date: 2020-08-26

  Online published: 2020-08-31

Supported by

the National Natural Science Foundation of China(81773562); the National Key Research Program of Proteins(2018YFE0195100); the Openning Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment(K2020000X)

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Abstract

With the expectation to find out novel and effective anti-tumor agents, a series of novel 2,4,6-substituted pyrimidine derivatives were synthesized and evaluated for their anti-tumor activity against four human cancer cells [SW-620 (human colon cancer cells), PC-3 (human prostate cancer cells), A549 (Human non-small cell lung cancer cells), MGC-803 (human gastric cancer cells)] using methyl thiazolyl tetrazolium (MTT) assay. Among tested compounds, N-((4-ethylphenyl)- carbamoyl)-2-((4-( p-tolylamino)-6-(trifluoromethyl)pyrimidin-2-yl)thio)acetamide (5i), 2-((4-((4-ethoxyphenyl)amino)-6-(tri- fluoromethyl)pyrimidin-2-yl)thio)- N-((4-ethylphenyl)carbamoyl)acetamide (5o) and N-((4-ethylphenyl)carbamoyl)-2-((4-((4- methoxyphenyl)amino)-6-(trifluoromethyl)pyrimidin-2-yl)thio)acetamide (5r) displayed strong antiproliferative activity on 4 tested cancer cell lines. In particular, compound5r has the highest inhibitive activity, and possessed the lowest IC50 value of 1.46 μmol/L towards SW-620 cells. Further mechanism research shows that compound5rinduces SW-620 apoptosis, arrests cell cycle at S phase. Molecular docking reveals that5r can bind well to the active site of epidermal growth factor receptor (EG-FR), and may be considered as a promising compound amenable for further investigation for the development of new anticancer agents.

Key words： pyrimidine derivative; synthesis; antitumor activity; cell cycle; apoptosis

Cite this article

Yang Zhang , Luye Zhang , Jikuan Wang , Limin Liu , Tao Wang , Na Li , Zhengjie Wang , Xiujuan Liu , Yaxin Chen , Danlin Zhao , Jiaxin Zheng , Lihong Shan , Hongmin Liu , Qiurong Zhang . Design, Synthesis and Antitumor Activity Evaluation Research of Novel 2,4,6-Substituted Pyrimidine Derivatives[J]. Chinese Journal of Organic Chemistry, 2021 , 41(1) : 310 -317 . DOI: 10.6023/cjoc202007067

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