Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Novel 5-Fluorouracil Derivatives: Synthesis and Cytotoxic Activity of 2-Butoxy-4-Substituted 5-Fluoropyrimidines

  • Sun, Jian (College of Chemical Engineering and Materials Science, Zhejiang University of Technology) ;
  • Zhang, Shi-Jie (Graduate School, Zhejiang Chinese Medical University) ;
  • Li, Hai-Bo (Nantong Center for Disease Control and Prevention) ;
  • Zhou, Wei (College of Pharmaceutical Science, Zhejiang University of Technology) ;
  • Hu, Wei-Xiao (College of Pharmaceutical Science, Zhejiang University of Technology) ;
  • Shan, Shang (College of Chemical Engineering and Materials Science, Zhejiang University of Technology)
  • Received : 2012.11.06
  • Accepted : 2013.02.05
  • Published : 2013.05.20
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Abstract

Twenty two new 5-fluorouracil (5-FU) derivatives, 2-butoxy-4-substituted 5-fluoropyrimidines, were synthesized and characterized by IR, $^1H$ NMR, MS, HRMS. All compounds were preliminarily evaluated by MTT assay on human liver BEL-7402 cancer cell line in vitro. Ten compounds were selected to test their cytotoxic activity against A549, HL-60 and MCF-7 cancer cell lines in vitro. These compounds were more sensitive to BEL-7402 than other cell lines, particularly, cytotoxic activity of compounds 6b, 6d-f, 6p, 6s-u were in sub-micromolar scale. The highest cytotoxic potency against A549, HL-60 and MCF-7 was shown by 2-butoxy-4-chloro-5-fluoropyrimidine (5) with $IC_{50}$ values of 0.10, 1.66 and $0.59{\mu}M$, respectively. Compounds 6d and 6e were effective against MCF-7 with $IC_{50}$ $9.73{\mu}M$ and HL-60 with $IC_{50}$ $8.83{\mu}M$, respectively.

Keywords

References

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