title: Ternary oxovanadium(IV) complexes with amino acid-Schiff base and polypyridyl derivatives: synthesis, characterization, and protein tyrosine phosphatase 1B inhibition.
abstract: To investigate the structure-activity relationship of vanadium complexes in inhibiting protein tyrosine phosphatase1B (PTP1B), eight mixed-ligand oxovanadium(IV) complexes, [V(IV)O(SalAla)(NN)] (H(2)SalAla for salicylidene alanine, NN for N,N'-donor heterocyclic base, namely, 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3), dipyrido[3,2-a:2',3'-c]phenazine (dppz, 4)), [V(IV)O(SalLys)(dpq)] (5), [V(IV)O(SalLys)(dppz)] (6), [V(IV)O(SalAsp)(dppz)], (7) and [V(IV)O(SalTrp)(dppz)] (8)), of which 3-8 are new, have been prepared and characterized by elemental analysis, infrared, UV-visible, electrospray ionization mass spectrometry and conductivity. The molar conductance data confirmed the non-electrolytic nature of the complexes in DMSO solution. The coordination in [V(IV)O (SalAla)(phen)] (2) was confirmed by X-ray crystal structure analysis. The oxidation state of V(IV) with d(1) configuration in 2 was confirmed by EPR. The speciation of VO-SalAla-phen in aqueous solution was investigated by potentiometric pH titrations. The results indicate that the main species are two ternary complexes at the pH range 7.0-7.4. Biochemical assays demonstrate that the mixed-ligand oxovanadium(IV) complexes are potent inhibitors of PTP1B with IC(50) values in the range of 62-597nM, approximately 3-10 fold weaker in potency than those of similar mixed-ligand oxovanadium(IV) complexes of salicylidene anthranilic acid (SAA) derivative with polypyridyl ligands, except complex 8, which exhibits comparable or better inhibition activity than those of the mixed-ligand oxovanadium(IV) complexes of SAA derivative with polypyridyl ligands. The results demonstrate that the structures of vanadium complexes influence the PTP1B inhibition activity. Kinetics assays reveal that complex 2 inhibits PTP1B in a competitive manner.
authors.affiliation: Institute of Molecular Science, the Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Shanxi University, Taiyuan, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Lu
authors.forename: Jinjun
authors.initials: J
authors.lastname: Yue
authors.forename: Caixia
authors.initials: C
authors.lastname: Yuan
authors.forename: Miaoli
authors.initials: M
authors.lastname: Zhu
authors.forename: Hong
authors.initials: H
authors.lastname: Han
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.forename: Maolin
authors.initials: M
authors.lastname: Guo
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014639:Vanadium / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D011725:Pyridines; D012545:Schiff Bases; D014639:Vanadium; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1