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

TitlePreparation and characterization of vanadyl complexes with bidentate maltol-type ligands; in vivo comparisons of anti-diabetic therapeutic potential
Publication TypeJournal Article
Year of Publication2003
AuthorsThompson, KH, Liboiron, BD, Bellman, Y, Setyawati, IA, Patrick, BO, Karunaratne, V, Rawji, G, Wheeler, J, Sutton, K, Bhanot, S, Cassidy, C, McNeill, JH, Yuen, VG, Orvig, C
JournalJournal of Biological Inorganic Chemistry
Volume8
Pagination66-74
Date PublishedJan
Type of ArticleArticle
ISBN Number0949-8257
KeywordsABSORPTION, BIS(MALTOLATO)OXOVANADIUM(IV) BMOV, CHEMISTRY, COORDINATION MODE, ETHYL MALTOL, IN-VITRO, INSULIN MIMETIC AGENT, insulin-enhancing activity, pharmacokinetics, PHOSPHATIDYLINOSITOL 3-KINASE, POLYMORPHIC FORMS, RATS, STZ-diabetic rat, vanadyl pyrone complexes
Abstract

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-C-14]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 C-14 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 C-14, liver) to 30 days (t(1/2)beta for V, bone). Curves of disappearance of plasma and whole blood C-14 and V diverged dramatically within the first hour after administration of the vanadium complex.

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