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

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.

Keywords

Zinc complex / Schiff base / Protein tyrosine phosphatase / Inhibitor

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