Chemical Research in Chinese Universities ›› 2019, Vol. 35 ›› Issue (2): 186-192.doi: 10.1007/s40242-019-8265-8

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

LI Xinhua1, YUAN Caixia1, LU Liping1, ZHU Miaoli1, XING Shu2, FU Xueqi2   

  1. 1. Key Laboratory of Chemical Biology and Molecular Engineering, Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, P. R. China;
    2. Edmond H. Fischer Signal Transduction Laboratory, College of Life Sciences, Jilin University, Changchun 130012, P. R. China
  • Received:2018-08-23 Revised:2019-01-08 Online:2019-04-01 Published:2019-04-30
  • Contact: YUAN Caixia, FU Xueqi E-mail:cxyuan@sxu.edu.cn;xingshu@jlu.edu.cn
  • Supported by:
    Supported by the National Natural Science Foundation of China(Nos.21471092, 21571118) and the Project of the Scientific Instrument Center of Shanxi University of China.

Abstract: 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.

Key words: Zinc complex, Schiff base, Protein tyrosine phosphatase, Inhibitor