Abstract
Six copper complexes of Schiff base ligands containing 3,5-substituted-4-salicylideneamino-3,5-dimethyl-1,2,4-triazole have been synthesized and well characterized. The structures of complexes 1 and 2 were determined by X-ray crystal analysis. Fluorescence and potentiometric study indicated that in the physiological pH range, one ligand was dissociated from the complexes to form 1:1 mononucleus copper complexes. The complexes potently inhibit 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 3-4 fold selectivity against PTP1B over TCPTP and PTP-MEG2, and 3-9 fold over SHP-1, but display almost no inhibition against Src homology phosphatase 2 (SHP-2). Complex 1 inhibits PTP1B with a competitive model with K(i) of 30 nM. Substitution with small groups at the phenyl of the ligand does not obviously influence the inhibitory ability of the complexes.
This journal is © The Royal Society of Chemistry 2011
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Coordination Complexes / chemical synthesis*
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Coordination Complexes / chemistry
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Copper / chemistry*
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Crystallography, X-Ray
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Enzyme Inhibitors / chemistry*
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Hydrogen Bonding
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Hydrogen-Ion Concentration
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Kinetics
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Molecular Conformation
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
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Protein Tyrosine Phosphatase, Non-Receptor Type 2 / antagonists & inhibitors
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Protein Tyrosine Phosphatase, Non-Receptor Type 2 / metabolism
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Protein Tyrosine Phosphatase, Non-Receptor Type 6 / antagonists & inhibitors
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Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
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Protein Tyrosine Phosphatases / antagonists & inhibitors*
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Protein Tyrosine Phosphatases / metabolism
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Schiff Bases / chemistry
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Stereoisomerism
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Triazoles / chemistry*
Substances
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Coordination Complexes
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Enzyme Inhibitors
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Schiff Bases
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Triazoles
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1,2,4-triazole
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Copper
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatase, Non-Receptor Type 2
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases