Ternary oxovanadium(IV) complexes of ONO-donor Schiff base and polypyridyl derivatives as protein tyrosine phosphatase inhibitors: Synthesis, characterization, and biological activities

Institute of Molecular Science, The Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Shanxi University, Taiyuan, China.
European Journal of Biochemistry (Impact Factor: 2.54). 04/2009; 14(6):841-51. DOI: 10.1007/s00775-009-0496-6
Source: PubMed


A series of oxovanadium complexes with mixed ligands, a tridentate ONO-donor Schiff base ligand [viz., salicylidene anthranilic acid (SAA)], and a bidentate NN ligand [viz., 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq), dipyrido[3,2-a:2′,3′-c]phenazine (dppz), or 7-methyldipyrido[3,2-a:2′,3′-c]phenazine (dppm)], have been synthesized and characterized by elemental analysis, electrospray ionization mass spectrometry, UV–vis spectroscopy, Fourier transform IR spectroscopy, EPR spectroscopy, and X-ray crystallography. Crystal structures of both complexes, [VIVO(SAA)(bpy)]·0.25bpy and [VIVO(SAA)(phen)]·0.33H2O, reveal that oxovanadium(IV) is coordinated with one nitrogen and two oxygen atoms from the Schiff base and two nitrogen atoms from the bidentate planar ligands, in a distorted octahedral geometry (VO3N3). The oxidation state of V(IV) with d
1 configuration was confirmed by EPR spectroscopy. The speciation of VO–SAA–bpy in aqueous solution was investigated by potentiomtreic pH titrations, and the results revealed that the main species are two ternary complexes at a pH range of 7.0–7.4, and one is the isolated crystalline complex. The complexes have been found to be potent inhibitors against human protein tyrosine phosphatase 1B (PTP1B) (IC50 approximately 30–61 nM), T-cell protein tyrosine phosphatase (TCPTP), and Src homology phosphatase 1 (SHP-1) in vitro. Interestingly, the [VIVO(SAA)(bpy)] complex selectively inhibits PTP1B over the other two phosphatases (approximate ninefold selectivity against SHP-1 and about twofold selectivity against TCPTP). Kinetics assays suggest that the complexes inhibit PTP1B in a competitive and reversible manner. These suggest that the complexes may be promising candidates as novel antidiabetic agents.
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    • "These ligands with ONNO donor atom set are well known to coordinate with various metal ions and this has attracted the interest of many authors [8] [9] [10] [11]. Many vanadium (IV) compounds are oxocomplexes containing the VO 2+ entity, and the geometry in the dioxo complexes has been confirmed by structure determinations [12] [13]. A few oxovanadium (V) complexes having the VO 3+ or the VO 2 + entity are characterized [14] where anions halides, alkoxide, peroxide, hydroxamates or aminocarboxylate are coordinated to satisfy the oxidation states. "
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    • "); inset the slope versus the concentration of complex 2 to determine the inhibition constant tyrosine phosphatase b (HPTPb). Our previous study shows that [VO(IV)(SAA)(bpy)] complexes selectively inhibit PTP1B over the other two phosphatases SHP-1 (Src homology phosphatase 1) and TCPTP (Tcell protein tyrosine phosphatase), nevertheless oxovanadium glutamate complex inhibits the PTP1B, TCPTP, SHP-1 and HePTP with almost same potency (Gao et al. 2009; Lu et al. 2010, 2011; Yuan et al. 2009, 2010). All these results indicate that although vanadium complexes generally lack specificity, ligands have some influence on the selectivity against different PTPs. "
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