pH-metric chemical speciation modeling and studies of in vitro antidiabetic effects of bis[(imidazolyl)carboxylato]oxidovanadium(IV) complexes

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...

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Veröffentlicht in:Journal of inorganic biochemistry 2015-04, Vol.145, p.11-18
Hauptverfasser: Gundhla, Isaac Z., Walmsley, Ryan S., Ugirinema, Vital, Mnonopi, Nandipha O., Hosten, Eric, Betz, Richard, Frost, Carminita L., Tshentu, Zenixole R.
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container_issue
container_start_page 11
container_title Journal of inorganic biochemistry
container_volume 145
creator Gundhla, Isaac Z.
Walmsley, Ryan S.
Ugirinema, Vital
Mnonopi, Nandipha O.
Hosten, Eric
Betz, Richard
Frost, Carminita L.
Tshentu, Zenixole R.
description 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. The bis[(imidazolyl)carboxylato]oxidovanadium(IV) complexes show potential as anti-diabetic agents. [Display omitted] •Oxidovanadium(IV) was stabilized by the imidazolyl-carboxylato moiety under physiological pH.•The isolated complexes were shown to activate glucose uptake in cell cultures.•The complexes showed inhibitory effect towards protein tyrosine phosphatase (PTP 1B).•The complexes also showed the inhibition of D-dimer formation.
doi_str_mv 10.1016/j.jinorgbio.2014.12.019
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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. The bis[(imidazolyl)carboxylato]oxidovanadium(IV) complexes show potential as anti-diabetic agents. 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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. 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The bis[(imidazolyl)carboxylato]oxidovanadium(IV) complexes show potential as anti-diabetic agents. [Display omitted] •Oxidovanadium(IV) was stabilized by the imidazolyl-carboxylato moiety under physiological pH.•The isolated complexes were shown to activate glucose uptake in cell cultures.•The complexes showed inhibitory effect towards protein tyrosine phosphatase (PTP 1B).•The complexes also showed the inhibition of D-dimer formation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25594947</pmid><doi>10.1016/j.jinorgbio.2014.12.019</doi><tpages>8</tpages></addata></record>
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subjects 3T3-L1 Cells
Adipocytes - drug effects
Adipocytes - metabolism
Animals
Anti-coagulative effects
Anti-diabetic effects
Anticoagulants - pharmacology
Coordination Complexes - chemistry
Coordination Complexes - pharmacology
Crystallography, X-Ray
Enzyme Inhibitors - pharmacology
Glucose - metabolism
Hydrogen-Ion Concentration
Hypoglycemic Agents - chemistry
Hypoglycemic Agents - pharmacology
In Vitro Techniques
Mice
Models, Chemical
Oxidovanadium(IV) complexes
Speciation
title pH-metric chemical speciation modeling and studies of in vitro antidiabetic effects of bis[(imidazolyl)carboxylato]oxidovanadium(IV) complexes
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