title: Ternary oxovanadium(IV) complexes of ONO-donor Schiff base and polypyridyl derivatives as protein tyrosine phosphatase inhibitors: synthesis, characterization, and biological activities.
abstract: 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.
authors.affiliation: Institute of Molecular Science, The Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Shanxi University, Taiyuan, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Yuan
authors.forename: Liping
authors.initials: L
authors.lastname: Lu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gao
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Wu
authors.forename: Maolin
authors.initials: M
authors.lastname: Guo
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Xueqi
authors.initials: X
authors.lastname: Fu
authors.forename: Miaoli
authors.initials: M
authors.lastname: Zhu
mesh_terms: D000042:Absorption; D004583:Electrons; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D046032:Microscopy, Energy-Filtering Transmission Electron; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011199:Potentiometry; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D014639:Vanadium / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D009942:Organometallic Compounds; D011725:Pyridines; D012545:Schiff Bases; D014639:Vanadium; D017027:Protein Tyrosine Phosphatases