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, [V(IV)O(SAA)(bpy)].0.25bpy and [V(IV)O(SAA)(phen)].0.33H(2)O, 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 (VO(3)N(3)). 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) (IC(50) approximately 30-61 nM), T-cell protein tyrosine phosphatase (TCPTP), and Src homology phosphatase 1 (SHP-1) in vitro. Interestingly, the [V(IV)O(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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Available from: Miaoli Zhu, Oct 13, 2015
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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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    ABSTRACT: Tetradentate Schiff base ligands (L), which were derived from the condensation of ethylenediamine with salicylaldehyde [Bis(5-bromosalicylaldehyde)ethylenediamine, bis(2-hydroxyacetophenone) ethylenediamine, Bis (benzoylacetone) ethylenediamine, Bis(2-hydroxy-1-napthaldehyde) ethylenediamine] and their complexes of VO3+ were synthesized and characterized by some physico-chemical studies; elemental, spectral (IR, UV, NMR), magnetic and conductance analyses. The elemental analysis data showed the formation of 1:1 [M:L] complexes. The obtained molar conductance values revealed their non- electrolytic nature. The results of magnetic measurements supported diamagnetic phenomenon for the complexes. The infrared spectral data displayed the main coordination sites of ligands towards VO3+ions. The electronic spectral results of the complexes showed π→π* (phenyl ring), n→π* (HC=N), CT transition. Based on analytical data octahedral geometry for the prepared complexes has been proposed. The antibacterial activity of the prepared complexes was also studied against some gram positive and gram negative bacteria, and a number of fungi. It is found that complexes are quite effective against tested bacteria whereas moderately effective to mycelia growth of the selected fungi.
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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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    ABSTRACT: The inhibitory effects of three biguanido-oxovanadium complexes ([VO(L(1-3))(2)]·nH(2)O: HL(1) = metformin, HL(2) = phenformin, HL(3) = moroxydine) against four protein tyrosine phosphatases (PTPs) and an alkaline phosphatase (ALP) were investigated. The complexes display strong inhibition against PTP1B and TCPTP (IC(50), 80-160 nM), a bit weaker inhibition against HePTP (IC(50), 190-410 nM) and SHP-1(IC(50), 0.8-3.3 μM) and much weaker inhibition against ALP (IC(50), 17-35 μM). Complex 3 is about twofold less potent against PTP1B, TCPTP and HePTP than complexes 1 and 2, while complex 2 inhibits SHP-1 more strongly (about three to fourfold) than the other two complexes. These results suggest that the structures of the ligands slightly influence the potency and selectivity against PTPs. The complexes inhibit PTP1B and ALP with a typical competitive type.
    Biology of Metals 05/2012; 25(3):599-610. DOI:10.1007/s10534-012-9548-4 · 2.50 Impact Factor
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    • "Kinetics analysis and the inhibitory effects of the copper complexes against the five PTPs were measured similarly as described previously (Yuan et al. 2009), using p-nitrophenol phosphate (pNPP) as the substrate. The assays were performed in 20 mM MOPS buffer, pH 7.2, containing 50 mM NaCl. "
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    ABSTRACT: A series of copper complexes with multi-benzimidazole derivatives, including mono- and di-nuclear, were synthesized and characterized by Fourier transform IR spectroscopy, UV-Vis spectroscopy, elemental analysis, electrospray ionization mass spectrometry. The speciation of Cu/NTB in aqueous solution was investigated by potentiometric pH titrations. Their inhibitory effects against human protein tyrosine phosphatase 1B (PTP1B), T-cell protein tyrosine phosphatase (TCPTP), megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2), srchomology phosphatase 1 (SHP-1) and srchomology phosphatase 2 (SHP-2) were evaluated in vitro. The five copper complexes exhibit potent inhibition against PTP1B, TCPTP and PTP-MEG2 with almost same inhibitory effects with IC(50) at submicro molar level and about tenfold weaker inhibition versus SHP-1, but almost no inhibition against SHP-2. Kinetic analysis indicates that they are reversible competitive inhibitors of PTP1B. Fluorescence study on the interaction between PTP1B and complex 2 or 4 suggests that the complexes bind to PTP1B with the formation of a 1:1 complex. The binding constant are about 1.14 × 10(6) and 1.87 × 10(6) M(-1) at 310 K for 2 and 4, respectively.
    Biology of Metals 05/2011; 24(6):993-1004. DOI:10.1007/s10534-011-9460-3 · 2.50 Impact Factor
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