Synthesis and molecular docking studies of novel pyrimidine derivatives as potential antibacterial agents

  • Xue-Qian Bai
  • Chun-Shi Li
  • Ming-Yue Cui
  • Ze-Wen Song
  • Xing-Yu Zhou
  • Chao Zhang
  • Yang Zhao
  • Tian-Yi ZhangEmail author
  • Tie-Yan JiangEmail author
Original Article


The present work describes the in vitro antibacterial evaluation of some new pyrimidine derivatives. Twenty-two target compounds were designed, synthesized and preliminarily explored for their antimicrobial activities. The antimicrobial assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungal including drug-resistant pathogens. Compound 7c presented the most potent inhibitory activities against Gram-positive bacteria (e.g., Staphylococcus aureus 4220), Gram-negative bacteria (e.g., Escherichia coli 1924) and the fungus Candida albicans 7535, with an MIC of 2.4 μmol/L. Compound 7c was also the most potent, with MICs of 2.4 or 4.8 μmol/L against four multidrug-resistant, Gram-positive bacterial strains. The toxicity evaluation of the compounds 7c, 10a, 19d and 26b was assessed in human normal liver cells (L02 cells). Molecular docking simulation and analysis suggested that compound 7c has a good interaction with the active cavities of dihydrofolate reductase (DHFR). In vitro enzyme study implied that compound 7c also displayed DHFR inhibition.

Graphic abstract


Pyrimidine Antibacterial activity Toxicity Molecular docking DHFR inhibition 



This work was supported by the Doctoral Foundation of Jilin Medical University (No. JYBS2018007), the Health Department of Jilin Province (2018ZC034) and the Department of Education of Jilin Province (No. JJKH20191070KJ).


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Xue-Qian Bai
    • 1
  • Chun-Shi Li
    • 2
  • Ming-Yue Cui
    • 2
  • Ze-Wen Song
    • 1
    • 3
  • Xing-Yu Zhou
    • 1
  • Chao Zhang
    • 1
  • Yang Zhao
    • 1
  • Tian-Yi Zhang
    • 1
    Email author
  • Tie-Yan Jiang
    • 4
    Email author
  1. 1.Jilin Medical UniversityJilinPeople’s Republic of China
  2. 2.The Third People’s Hospital of DalianDalianPeople’s Republic of China
  3. 3.Department of PharmaryYanbian UniversityYanjiPeople’s Republic of China
  4. 4.Changning Branch of Shanghai Municipal Public Security BureauShanghaiPeople’s Republic of China

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