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Design, synthesis, and biologic evaluation of some novel N-arylpyrazole derivatives as cytotoxic agents

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Abstract

A novel series of N-arylpyrazole derivatives (5a–5d, 7a–7c) has been designed and synthesized via aromatic substitution reaction of N-nonsubstituted pyrazoles with 4-fluoronitrobenzene in the presence of base. The structures of these compounds were established on the basis of elemental (C, H, and N) and spectral analysis (1H NMR, 13C NMR, HRMS, and FT-IR). All the compounds were tested for their cytotoxic activity in vitro against four human tumor cell lines: carcinoma (Bel-7402), nasopharyngeal carcinoma (KB), immature granulocyte leukemia (HL-60), and gastrocarcinoma (BGC-823) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results showed that most of the obtained compounds exhibited promising cytotoxicity against tested carcinoma cell lines with low IC50 values. The bis-pyrazole derivative 7c, bearing alkoxy group on the 5-position of phenyl ring, was the most effective one. It is inhibition of cell growth of Bel-7402 cells was 1.5-fold higher than that found for cisplatin. And, also mono-pyrazole derivatives 5a and 5b, decorated with trifluoromethyl group on the phenyl ring, displayed better cytotoxicity than that of cisplatin against Bel-7402 cell line.

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Acknowledgments

This work was supported by the National Basic Research 973 Program (Grant No. 2010CB534913), Hebei Provincial Natural Science Foundation of China-Shijiazhuang Pharmaceutical Group (CSPC) Foundation (B2011201174), Hebei Province Nature Science Fund for Distinguished Young Scholars (B2011201164), the Nature Science Fund of Hebei Province (B2011201135), the Key Basic Research Special Foundation of Science Technology Ministry of Hebei Province (11966412D, 12966418D), and Open Fund of Key Laboratory of Chemical Biology of Hebei Province (No. 09265631D-7).

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Authors and Affiliations

  1. Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis, Ministry of Education, College of Chemistry and Environmental Science, Hebei University, Baoding, 071002, People’s Republic of China

    Shengjie Xu, Shenghui Li, Yonghe Tang, Jinchao Zhang, Shuxiang Wang, Chuanqi Zhou & Xiaoliu Li

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  1. Shengjie Xu
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  2. Shenghui Li
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  3. Yonghe Tang
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  4. Jinchao Zhang
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  5. Shuxiang Wang
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  7. Xiaoliu Li
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Correspondence to Shenghui Li or Jinchao Zhang.

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Xu, S., Li, S., Tang, Y. et al. Design, synthesis, and biologic evaluation of some novel N-arylpyrazole derivatives as cytotoxic agents. Med Chem Res 22, 5610–5616 (2013). https://doi.org/10.1007/s00044-013-0552-1

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