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Chinese Journal of Organic Chemistry >

2022 , Vol. 42 >Issue 6: 1677 - 1686

DOI: https://doi.org/10.6023/cjoc202201048

ARTICLES

Synthesis and Antiproliferative Activity of 2,4,5,6-Tetrasubstituted Pyrimidine Derivatives Containing Anisole

  • Chao Gao ,
  • Xiaojie Si ,
  • Lingling Chi ,
  • Hao Wang ,
  • Honglin Dai ,
  • Limin Liu ,
  • Zhengjie Wang ,
  • Yang Zhang ,
  • Tao Wang ,
  • Yaochuan Zhou ,
  • 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 & Quality and Safety Evaluation, 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 450001
*E-mail: ;
;

Received date: 2022-01-28

  Revised date: 2022-03-08

  Online published: 2022-03-22

Supported by

National Natural Science Foundation of China(U21A20416); Opening Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment(K2020000X)

Fold

Abstract

In order to find efficient new anti-tumor drugs, a series of 2,4,5,6-tetrasubstituted pyrimidine derivatives containing anisole structure were designed, synthesized and evaluated for antiproliferative activity against four human cancer cell lines of PC-3, MGC-803, MCF-7 and HGC-27 using methyl thiazolyl tetrazolium (MTT) assay. Most of compounds displayed moderate to excellent antiproliferative activity against the four human tumor cell lines, among which the compound 5-ethyl-6- ((4-methoxyphenyl)thio)-N4-(3,4,5-trimethoxyphenyl)pyrimidine-2,4-diamine (14t) showed the best antiproliferative activity on HGC-27 cells, with IC50 value of (0.98±0.12) μmol•L–1, the antiproliferative activity is significantly better than that of the positive control 5-fluorouracil. Further research on anti-tumor mechanism showed that compound 14t could significantly inhibit the colony formation and migration of HGC-27 cells and induce apoptosis. At the same time, compound 14t can down-regulate the expression of anti-apoptotic protein Bcl-2 and up-regulate the expression of pro-apoptotic proteins Bax and P53.

Key words： pyrimidine; anisole; synthesis; antiproliferative activity

Cite this article

Chao Gao , Xiaojie Si , Lingling Chi , Hao Wang , Honglin Dai , Limin Liu , Zhengjie Wang , Yang Zhang , Tao Wang , Yaochuan Zhou , Jiaxin Zheng , Yu Ke , Hongmin Liu , Qiurong Zhang . Synthesis and Antiproliferative Activity of 2,4,5,6-Tetrasubstituted Pyrimidine Derivatives Containing Anisole[J]. Chinese Journal of Organic Chemistry, 2022 , 42(6) : 1677 -1686 . DOI: 10.6023/cjoc202201048

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