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Synthesis and antitumor activity of novel phenylhydrazonopyrazolone derivatives and molecular dynamics simulations

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Abstract

SHP2 is a new promising target for anti-cancer drug discovery. A series of novel phenylhydrazonopyrazolone derivatives was synthesized by a more convenient method, and their chemical structures were characterized by various spectroscopic methods. The inhibitory effects of these compounds on SHP2 enzyme and SHP2-dependent cancer cell H1975 were evaluated. The compound 11f with IC50 value of 3.38 μmol/L exhibited more potent antitumor activity against H1975 cell than GS-493 (IC50 = 20.92 μmol/L). Molecular dynamics simulation of compound 11f displayed a possible mode of interaction between this compound and SHP2 enzyme.

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  1. http://vina.scripps.edu/, version 1.1.2, platform independent, Apache license.

  2. http://www.rcsb.org/pdb/home/home.do.

  3. http://adfr.scripps.edu/AutoDockFR/agfr.html, version 1.0, platform independent, LGPL OpenSource software license.

  4. http://www.gromacs.org/, version 5.1.2, platform independent, GNU LGPL 2.1.

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Acknowledgements

This work was supported by the National Youth Innovative Training Fund for College Students of Wuhan University of Science and Technology [Grant No. 201510488010].

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Author notes

  1. Xia-min Hu and Zhi-wen Cui have contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China

    Xia-min Hu

  2. Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, 430065, Hubei Province, China

    Xia-min Hu, Zhi-wen Cui, Wei Dong, Yue Zhu, Cheng-zhi Gao, Shi-qiang Xu, Qiong Yuan, Zhi-jun Yu & Zhen-li Min

  3. Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, 430065, Hubei Province, China

    Qiong Yuan & Zhen-li Min

  4. New Drugs Innovation and Development Institute, Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, 430065, Hubei Province, China

    Qiong Yuan & Zhen-li Min

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  1. Xia-min Hu
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Correspondence to Zhen-li Min.

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Hu, Xm., Cui, Zw., Dong, W. et al. Synthesis and antitumor activity of novel phenylhydrazonopyrazolone derivatives and molecular dynamics simulations. Res Chem Intermed 44, 5107–5122 (2018). https://doi.org/10.1007/s11164-018-3412-2

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  • DOI: https://doi.org/10.1007/s11164-018-3412-2

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