title: pH-metric chemical speciation modeling and studies of in vitro antidiabetic effects of bis[(imidazolyl)carboxylato]oxidovanadium(IV) complexes.
abstract: A range of bidentate N,O-donor ligands of the imidazolyl-carboxylate moiety, which partially mimic naturally occurring bioligands, were prepared and reacted with the oxidovanadium(IV) ion to form the corresponding bis-coordinated oxidovanadium(IV) complexes. The aqueous pH-metric chemical speciation was investigated using glass electrode potentiometry, which allowed for the determination of protonation and stability constants of the ligands and complexes, respectively. The species distribution diagrams generated from this information gave evidence that the bis[(imidazolyl)carboxylato]oxovanadium(IV) complexes possess a broad pH-metric stability. The complexes improved glucose uptake in cell cultures using 3T3-L1 adipocytes, C2C12 muscle cells and Chang liver cells. The PTP inhibition studies indicated that the mechanism underlying insulin-stimulated glucose uptake was possibly via the protein tyrosine phosphorylation through the inhibition of the protein tyrosine phosphatase 1B (PTP 1B). The vanadium compounds also demonstrated the inhibition of D-dimer formation, suggesting that these compounds could potentially relieve a hypercoagulative state in diabetic patients.
authors.affiliation: Department of Chemistry, Rhodes University, PO Box 94, Grahamstown 6140, South Africa.
authors.forename: Isaac Z
authors.initials: IZ
authors.lastname: Gundhla
authors.affiliation: Department of Chemistry, Rhodes University, PO Box 94, Grahamstown 6140, South Africa.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Walmsley
authors.affiliation: Department of Chemistry, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031, South Africa.
authors.forename: Vital
authors.initials: V
authors.lastname: Ugirinema
authors.affiliation: Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031, South Africa.
authors.forename: Nandipha O
authors.initials: NO
authors.lastname: Mnonopi
authors.affiliation: Department of Chemistry, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031, South Africa.
authors.forename: Eric
authors.initials: E
authors.lastname: Hosten
authors.affiliation: Department of Chemistry, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031, South Africa.
authors.forename: Richard
authors.initials: R
authors.lastname: Betz
authors.affiliation: Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031, South Africa. Electronic address: carminita.frost@nmmu.ac.za.
authors.forename: Carminita L
authors.initials: CL
authors.lastname: Frost
authors.affiliation: Department of Chemistry, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031, South Africa. Electronic address: zenixole.tshentu@nmmu.ac.za.
authors.forename: Zenixole R
authors.initials: ZR
authors.lastname: Tshentu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008956:Models, Chemical
chemical_list: D000925:Anticoagulants; D056831:Coordination Complexes; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D005947:Glucose
keywords: Anti-coagulative effects; Anti-diabetic effects; Oxidovanadium(IV) complexes; Speciation