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Synthesis, biological evaluation, and molecular docking studies of pyrazolyl-acylhydrazone derivatives as novel anticancer agents

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Abstract

A series of pyrazolyl-acylhydrazone derivatives (1e–20e) have been designed and synthesized and their biologic activities were also evaluated for telomerase inhibition and tumor cell antiproliferation. Among all the compounds, 12e showed the most potent activity in vitro, which inhibited the growth of MCF-7 and B16-F10 cell lines with IC50 values of 0.57 ± 0.03 and 0.49 ± 0.07 μM, respectively. Compound 12e also exhibited significant telomerase inhibitory activity (IC50 = 1.9 ± 0.43 μM). The result of flow cytometry demonstrated that compound 12e induced cell apoptosis. Docking simulation was performed to insert compound 12e into the crystal structure of telomerase at ATP binding site to determine the probable binding model. Based on the preliminary results, compound 12e with potent inhibitory activity in tumor growth may be a potential anticancer agent.

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Acknowledgments

This work was financed by National Natural Science Foundation of China (No. J1103512).

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Authors and Affiliations

  1. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, People’s Republic of China

    Man Xing, Ting-Ting Zhao, Yu-Jia Ren, Na-Na Peng, Xian-Hui Yang, Xi Li, Hui Zhang, Li-Rong Zhang & Hai-Liang Zhu

  2. School of Materials Science and Engineering, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China

    Gao-Qi Liu

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  1. Man Xing
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  2. Ting-Ting Zhao
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  3. Yu-Jia Ren
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  7. Hui Zhang
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  9. Li-Rong Zhang
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  10. Hai-Liang Zhu
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Correspondence to Hai-Liang Zhu.

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Man Xing and Ting-Ting Zhao equally contributed to this paper.

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Xing, M., Zhao, TT., Ren, YJ. et al. Synthesis, biological evaluation, and molecular docking studies of pyrazolyl-acylhydrazone derivatives as novel anticancer agents. Med Chem Res 23, 3274–3286 (2014). https://doi.org/10.1007/s00044-014-0909-0

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  • DOI: https://doi.org/10.1007/s00044-014-0909-0

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