Preparation and characterization of vanadyl complexes with bidentate maltol-type ligands; in vivo comparisons of anti-diabetic therapeutic potential

A series of 2-alkyl-3-hydroxy-4-pyrone oxovanadium(IV) compounds has been synthesized, characterized, and tested for bioactivity as potential insulin-enhancing agents. The vanadyl complexes, bis(maltolato)oxovanadium(IV), BMOV, bis(ethylmaltolato)oxovanadium(IV), BEOV, and bis(isopropylmaltolato)oxo...

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Bibliographic Details
Published in:Journal of biological inorganic chemistry 2003-01, Vol.8 (1-2), p.66-74
Main Authors: Thompson, Katherine H, Liboiron, Barry D, Sun, Yan, Bellman, Karycia D D, Setyawati, Ika A, Patrick, Brian O, Karunaratne, Veranja, Rawji, Gulnar, Wheeler, Jeffrey, Sutton, Kymberley, Bhanot, Sanjay, Cassidy, Carrie, McNeill, John H, Yuen, Violet G, Orvig, Chris
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Blood Glucose - metabolism
Carbon Radioisotopes
Diabetes Mellitus, Experimental - blood
Diabetes Mellitus, Experimental - drug therapy
Female
Half-Life
Hypoglycemic Agents - chemical synthesis
Hypoglycemic Agents - chemistry
Hypoglycemic Agents - pharmacokinetics
Hypoglycemic Agents - pharmacology
Injections, Intraperitoneal
Ligands
Models, Molecular
Organometallic Compounds - chemical synthesis
Organometallic Compounds - chemistry
Organometallic Compounds - pharmacokinetics
Organometallic Compounds - pharmacology
Rats
Rats, Sprague-Dawley
Vanadium - blood
Vanadium - chemistry
Vanadium - pharmacokinetics
Vanadium - pharmacology
Vanadium Compounds - pharmacology
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Summary:A series of 2-alkyl-3-hydroxy-4-pyrone oxovanadium(IV) compounds has been synthesized, characterized, and tested for bioactivity as potential insulin-enhancing agents. The vanadyl complexes, bis(maltolato)oxovanadium(IV), BMOV, bis(ethylmaltolato)oxovanadium(IV), BEOV, and bis(isopropylmaltolato)oxovanadium(IV), BIOV, were compared against vanadyl sulfate for glucose-lowering ability, when administered i.p. to STZ-diabetic rats, at a one-time dose of 0.1 mmol kg(-1)body weight. Blood levels of vanadium were determined at regular intervals, to 72 h, following i.p. injection. All complexes tested exceeded vanadyl sulfate in glucose-lowering ability; this effect was not correlated, however, with blood vanadium levels. Analysis of the pharmacokinetics of the disappearance of [ethyl-1-(14)C]BEOV after an oral gavage dose (50 mg kg(-1), 0.144 mmol kg(-1), in a 10 mL kg(-1) volume of 1% CMC solution) indicated clearly that metal ion-ligand dissociation took place relatively soon after oral ingestion of the complex. Half-lives of fast phase uptake and slow phase disappearance for (14)C and V were calculated from a two-compartment model for whole blood, plasma, liver, kidney, bone, small intestine, and lung, ranging from 17 min ( t(1/2)alpha for (14)C, liver) to 30 days ( t(1/2)beta for V, bone). Curves of disappearance of plasma and whole blood (14)C and V diverged dramatically within the first hour after administration of the vanadium complex.
ISSN:0949-8257
1432-1327
DOI:10.1007/s00775-002-0388-5