Chemical Research in Chinese Universities

, Volume 35, Issue 2, pp 186–192 | Cite as

Exploration of Zinc(II) Complexes as Potent Inhibitors Against Protein Tyrosine Phosphatase 1B

  • Xinhua Li
  • Caixia YuanEmail author
  • Liping Lu
  • Miaoli Zhu
  • Shu XingEmail author
  • Xueqi Fu


Although protein tyrosine phosphatases(PTPs) do not contain any metals, their activities can be inhibited by some metal complexes. Here we investigated the inhibition of two zinc complexes with Schiff base ligands against PTPs activity to explore their effect on the cellular metabolism. It has been found that they are potent inhibitors against four recombinant PTPs, including protein tyrosine phosphatase 1B(PTP1B), T cell protein tyrosine phosphatase( TCPTP), megakaryocyte protein tyrosine phosphatase 2(PTP-MEG2), and Src-homology phosphatase 1(SHP-1), with exception of Src-homology phosphatase 2(SHP-2). Moreover, they showed moderate selective inhibition against PTP1B with the IC50 values of 0.15 and 0.36 μmol/L. Meanwhile, the complexes also inhibited cellular phosphatase activities efficiently. Comparing the inhibitory potency over PTPs mediated by the zinc ion, we found that zinc complexes might be easily developed into potent and selective inhibitors against certain PTP by rationally modifying the organic ligands moieties.


Zinc complex Schiff base Protein tyrosine phosphatase Inhibitor 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Alonso A., Sasin J., Bottini N., Friedberg I., Osterman A., Godzik A., Hunter T., Dixon J., Mustelin T., Cell, 2004, 117(6), 699CrossRefGoogle Scholar
  2. [2]
    Andersen J. N., Mortensen O. H., Peters G. H., Drake P. G., Iversen L. F., Olsen O. H., Jansen P. G., Andersen H. S., Tonks N. K., Moller N. P. H., Mol. Cell. Biol., 2001, 21(21), 7117CrossRefGoogle Scholar
  3. [3]
    Shivani V., Saurabh S., Curr. Mol. Pharmacol., 2018, 11(3), 191CrossRefGoogle Scholar
  4. [4]
    Hale A. J., ter Steege E., den Hergog J., Dev. Biol., 2017, 428(2), 283CrossRefGoogle Scholar
  5. [5]
    Bollu L. R., Mazumdar A., Savage M. I., Brown P. H., Clin. Cancer Res., 2017, 23(9), 2136CrossRefGoogle Scholar
  6. [6]
    Ruddraraju K. V., Zhang Z. Y., Mol. Biosyst., 2017, 13, 1257CrossRefGoogle Scholar
  7. [7]
    Zhang C. L., Sun X. N., Li C. Y., Cai J. Y., Wang J., Li Y. Z., Wang H. Y., Chem. J. Chinese Universities, 2017, 38(10), 1764Google Scholar
  8. [8]
    Chai Q., Shen Q., Ma L. P., Wang X., Meng T., Li J. Y., Li J., Shen J. K., Chem. J. Chinese Universities, 2011, 32(2), 306Google Scholar
  9. [9]
    Lu L. P., Zhu M. L., Antioxid. Redox Signal., 2014, 20(14), 2210CrossRefGoogle Scholar
  10. [10]
    Jia Y., Lu L., Zhu M., Yuan C., Xing S., Fu X., Eur. J. Med. Chem., 2017, 128, 287CrossRefGoogle Scholar
  11. [11]
    Li Y. H., Yuan C. X., Lu L. P., Zhu M. L., Fu X. Q., Xing S., Gao Z. Q., Chem. J. Chinese Universities, 2016, 37(12), 2138Google Scholar
  12. [12]
    Maywald M., Wessels I., Rink L., Int. J. Mol. Sci., 2017, 18(11), 2222CrossRefGoogle Scholar
  13. [13]
    Maret W., Biometals, 2013, 26(2), 197CrossRefGoogle Scholar
  14. [14]
    Bellomo E., Massarotti A., Hogstrand C., Maret W., Metallomics, 2014, 6(7), 1229CrossRefGoogle Scholar
  15. [15]
    Haase H., Maret W., Biometals, 2005, 18(4), 333CrossRefGoogle Scholar
  16. [16]
    Wilson M., Hogstrand C., Maret W., J. Biol. Chem., 2012, 287(12), 9322CrossRefGoogle Scholar
  17. [17]
    Price K. A., Caragounis A., Paterson B. M., Filiz G., Volitakis I., Masters C. L., Barnham K. J., Donnelly P. S., Crouch P. J., White A. R., J. Med. Chem., 2009, 52(21), 6606CrossRefGoogle Scholar
  18. [18]
    Yuan C., Lu L., Gao X., Wu Y., Guo M., Li Y., Fu X., Zhu M., J. Biol. Inorg. Chem., 2009, 14(6), 841CrossRefGoogle Scholar
  19. [19]
    Zhang L., Zhang S. T., Zhang X. P., Sun J., Wang Y. S., Liu Y. L., Xue M. M., Wang Z., Xing S., Ma J. F., Li W. N., Fu X. Q., Chem. Res. Chinese Universities, 2013, 29(4), 730CrossRefGoogle Scholar
  20. [20]
    Yuan C. X., Lan S. F., Lu L. P., Chin. J. Inorg. Chem., 2015, 31(5), 915Google Scholar
  21. [21]
    Clague M. J., Keder N. L, Butler A., Inorg. Chem., 1993, 32(22), 4754CrossRefGoogle Scholar
  22. [22]
    Sheldrick G. M., Correction Software, University of Göttingen, Göttingen, 1996Google Scholar
  23. [23]
    Sheldrick G. M., Program for the Solution of Crystal Structure, University of Göttingen, Göttingen, 1997Google Scholar
  24. [24]
    Farrugia L. J., J. Appl. Cryst., 1997, 30, 565CrossRefGoogle Scholar
  25. [25]
    Ma L., Lu L., Zhu M., Wang Q., Li Y., Xing S., Fu X., Gao Z., Dong Y., Dalton Trans., 2011, 40(24), 6532CrossRefGoogle Scholar
  26. [26]
    Woolley E. M., Tomkins J., Hepler L. G., J. Sol. Chem., 1972, 1, 341CrossRefGoogle Scholar
  27. [27]
    Yuan C., Lu L., Wu Y., Liu Z., Guo M., Xing S., Fu X., Zhu M., J. Inorg. Biochem., 2010, 104(9), 978CrossRefGoogle Scholar
  28. [28]
    Alain M., Michel B., Michel D., J. Chem. Edu., 1986, 63, 365CrossRefGoogle Scholar
  29. [29]
    Kumar S. M., Rajesh J., Anitha K., Dhahagani K., Marappan M., Gandhi N. I., Rajagopal G., Spectrochim. Acta A, 2015, 142(5), 292Google Scholar
  30. [30]
    Gans P., Sabatini A., Vacca A., J. Chem. Soc., Dalton Trans., 1985, 1195Google Scholar
  31. [31]
    Yuan C., Zhu M., Wang Q., Lu L., Xing S., Fu X., Jiang Z., Zhang S., Li Z., Zhu R., Ma L., Xu L., Chem. Commun., 2012, 48, 1153CrossRefGoogle Scholar
  32. [32]
    Ding F., Zhao G., Huang J., Sun Y., Zhang L., Eur. J. Med. Chem., 2009, 44(10), 4083CrossRefGoogle Scholar
  33. [33]
    Haj F. G., Markova B., Klaman L. D., Bohmer F. D., Neel B. G., J. Biol. Chem., 2003, 278, 739CrossRefGoogle Scholar
  34. [34]
    Zhang S., Chen L., Luo Y., Gunawan A., Lawrence D. S., Zhang Z. Y., J. Am. Chem. Soc., 2009, 131, 13072CrossRefGoogle Scholar
  35. [35]
    Yuan T., Wang Y., Zhao Z. J., Gu H., J. Bio. Chem., 2010, 285(20), 14861CrossRefGoogle Scholar
  36. [36]
    Chen Q., Lu L. P., Chinese J. Inorg. Chem., 2016, 32(6), 1001Google Scholar
  37. [37]
    Li Y. H., Lu L. P., Zhu M. L., Yuan C. X., Feng S. S., Gao Z. Q., Chinese J. Struct. Chem., 2017, 36(2), 316Google Scholar
  38. [38]
    Seale A. P., de Jesus L. A., Kim S., Choi Y., Lim H. B., Hwang C., Kim Y., Biotechnol. Lett., 2005, 27, 221CrossRefGoogle Scholar

Copyright information

© Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH 2019

Authors and Affiliations

  1. 1.Key Laboratory of Chemical Biology and Molecular Engineering, Ministry of Education, Institute of Molecular ScienceShanxi UniversityTaiyuanP. R. China
  2. 2.Edmond H. Fischer Signal Transduction Laboratory, College of Life SciencesJilin UniversityChangchunP. R. China

Personalised recommendations