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

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

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.

Keywords

Phenylhydrazonopyrazolone Anticancer activity SHP2 inhibitor GS-493 Molecular dynamics simulation 

Notes

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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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Xia-min Hu
    • 1
    • 2
  • Zhi-wen Cui
    • 2
  • Wei Dong
    • 2
  • Yue Zhu
    • 2
  • Cheng-zhi Gao
    • 2
  • Shi-qiang Xu
    • 2
  • Qiong Yuan
    • 2
    • 3
    • 4
  • Zhi-jun Yu
    • 2
  • Zhen-li Min
    • 2
    • 3
    • 4
  1. 1.College of PharmacyShanghai University of Medicine and Health SciencesShanghaiChina
  2. 2.Department of Pharmacy, College of MedicineWuhan University of Science and TechnologyWuhanChina
  3. 3.Hubei Province Key Laboratory of Occupational Hazard Identification and ControlWuhan University of Science and TechnologyWuhanChina
  4. 4.New Drugs Innovation and Development Institute, Department of Pharmacy, College of MedicineWuhan University of Science and TechnologyWuhanChina

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