Synthesis and evaluation of oxovanadium(IV) complexes of Schiff-base condensates from 5-substituted-2-hydroxybenzaldehyde and 2-substituted-benzenamine as selective inhibitors of protein tyrosine phosphatase 1B

Dalton Trans. 2012 Aug 28;41(36):11116-24. doi: 10.1039/c2dt30198a.

Abstract

Five oxovanadium(IV) complexes, which were divided into two groups, [V(IV)O(bhbb, nhbb)(H(2)O)(2)] (tridentate ligands: H(2)bhbb = 2-(5-bromo-2-hydroxylbenzylideneamino)benzoic acid, 1; H(2)nhbb = 2-(5-nitro-2-hydroxylbenzylideneamino)benzoic acid, 2) and [V(IV)O(cpmp, bpmp, npmp)(2)] (bidentate ligands: Hcpmp = 4-chloro-2-((phenylimino)methyl)phenol, 3; Hbpmp = 4-bromo-2-((phenylimino)methyl)phenol, 4; Hnpmp = 4-nitro-2-((phenylimino)methyl) phenol, 5) have been prepared and characterized by elemental analysis, infrared, UV-visible and electrospray ionization mass spectrometry. The coordination in [V(IV)O(bhbb)(H(2)O)(2)] (1) was confirmed by X-ray crystal structure analysis. The oxidation state of V(IV) with d(1) configuration in 1-5 was confirmed by EPR. The speciation of VO/H(2)bhbb in methanol-aqueous solution was investigated by potentiometric pH titrations. The result indicated that the main species were [V(IV)O(bhbb)(OH)](-) and [V(IV)O(bhbb)(OH)(2)](2-) at the pH range 7.0-7.4. The structure-activity relationship of the vanadium complexes in inhibiting protein tyrosine phosphatases (protein tyrosine phosphatase 1B, PTP1B; T-cell protein tyrosine phosphatase, TCPTP; megakaryocyte protein-tyrosine phosphatase, PTP-MEG2; Src homology phosphatase 1, SHP-1 and Src homology phosphatase 2, SHP-2) was investigated. The oxovanadium(IV) complexes were potent inhibitors of PTP1B, TCPTP, PTP-MEG2, SHP-1 and SHP-2, but exhibited different inhibitory abilities over different PTPs. Complexes 2 and 4 displayed better selectivity to PTP1B over the other four PTPs. Kinetic data showed that complex 2 inhibited PTP1B, TCPTP and SHP-1 with a noncompetitive inhibition mode, but a classical competitive inhibition mode for PTP-MEG2 and SHP-2. The results demonstrated that both the structures of vanadium complexes and the conformations of PTPs influenced PTP inhibition activity. The proper modification of the organic ligand moieties may result in screening potent and selective vanadium-based PTP1B inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Benzaldehydes / chemistry
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemistry*
  • Kinetics
  • Molecular Conformation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Schiff Bases / chemistry*
  • Vanadates / chemistry*

Substances

  • Amines
  • Benzaldehydes
  • Coordination Complexes
  • Enzyme Inhibitors
  • Recombinant Proteins
  • Schiff Bases
  • oxovanadium IV
  • Vanadates
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • benzaldehyde