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Vanadyl-biguanide complexes as potential synergistic insulin mimics

TitleVanadyl-biguanide complexes as potential synergistic insulin mimics
Publication TypeJournal Article
Year of Publication1999
AuthorsWoo, LCY, Yuen, VG, Thompson, KH, McNeill, JH, Orvig, C
JournalJournal of Inorganic Biochemistry
Volume76
Pagination251-257
Date PublishedSep
Type of ArticleArticle
ISBN Number0162-0134
Keywordsbiguanide, BIS(MALTOLATO)OXOVANADIUM(IV), BMOV, coordination complex, GLUCOSE-LOWERING PROPERTIES, insulin mimic, MECHANISM, METFORMIN, MIMETIC AGENT, MUSCLE, RATS, VANADIUM
Abstract

Vanadium has well-documented blood-glucose-lowering properties both in vitro and in vivo. The design of new oxovanadium(IV) coordination compounds, intended for use as insulin-enhancing agents in the treatment of diabetes mellitus, can potentially benefit from a synergistic approach, in which the whole complex has more than an additive effect from its component parts. Biguanides, most importantly metformin, are oral hypoglycemic agents used today to treat type 2 diabetes mellitus. In this study, biguanide, metformin, and phenformin, all biguanides, were coordinated to oxovanadium(IV) to form potential insulin-enhancing compounds. Highly colored, air-stable, bis(biguanidato)oxovanadium(IV), [VO(big)(2)], bis(N’,N’-dimethylbiguanidato)oxovanadium(IV) [VO(metf)(2)], and bis(beta-phenethyl-biguanidato)oxovanadium(IV), [VO(phenf)(2)], were prepared. Solvation with dimethylsulfoxide occurred with VO(metf)(2) to form a six-coordinate complex. Precursor ligands and oxovanadium(IV) coordination complexes were characterized by infrared spectroscopy, mass spectrometry, elemental analyses, magnetic susceptibility, and, where appropriate, H-1 NMR spectroscopy. Biological testing with VO(metf)(2), a representative compound, for insulin-enhancing potential included acute (72 h) administration, both by intraperitoneal (i.p.) injection and by oral gavage (p.o,) in streptozotocin (STZ)-diabetic rats. VO(metf)(2) administration resulted in significant blood-glucose lowering at doses of 0.12 mmol kg(-1) i.p. and 0.60 mmol kg(-1) p.o. (previously established as ED50 doses for organically chelated oxovanadium(IV) complexes); however, no positive associative effects due to the presence of biguanide in the complex were apparent. (C) 1999 Elsevier Science Inc. All rights reserved.

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