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Vanadyl-thiazolidinedione combination agents for diabetes therapy

TitleVanadyl-thiazolidinedione combination agents for diabetes therapy
Publication TypeJournal Article
Year of Publication2003
AuthorsStorr, T, Mitchell, D, Buglyo, P, Thompson, KH, Yuen, VG, McNeill, JH, Orvig, C
JournalBioconjugate Chemistry
Volume14
Pagination212-221
Date PublishedJan-Feb
Type of ArticleArticle
ISBN Number1043-1802
KeywordsAGENT, ANTIHYPERGLYCEMIC, BIOLOGICAL-ACTIVITY, BIS(MALTOLATO)OXOVANADIUM(IV), BLOOD-GLUCOSE, COMPLEXES, DERIVATIVES, GLUCOSE-LOWERING PROPERTIES, INSULIN MIMETIC AGENT, RAT ADIPOCYTES, TROGLITAZONE
Abstract

A series of vanadium compounds, chelated by ligands containing a thiazolidinedione moiety as an additional insulin-enhancing component, were produced in this study to create potentially synergistic compounds. A set of four bifunctional ligand precursors were synthesized: (+/-)-5-4-[(5-hydroxy-4-oxo-4H-pyran-2-ylmethyl)amino]benzylthiazolidi ne-2,4-dione (HL1), (+/-)-5-4-[5-hydroxy-1-methyl-4-oxo-1,4-dihydro-pyridin-2-ylmethyl)amin o]benzylthiazolidine-2,4-dione (HL2) 5-[4-(5-hydroxy-4-oxo-4H-pyran-2-ylmethoxy)benzylidenelthiazolidine-2,4- dione (HL1), and (+/-)-5-4-(5-hydroxy-4-oxo-4H-pyran-2-ylmethoxy)benzyl]thiazolidine-2,4 -dione (HL4), each containing a metal chelating portion as well as a thiazolidinedione moiety. From this set of ligand precursors, air-stable VO(L-1)(2), VO(L-3)(2), and VO(L-4)(2) were prepared. The four ligand precursors and three complexes were tested for insulin-enhancing potential in STZ-diabetic rats and compared to rosiglitazone and BMOV, respectively. Both the ligand precursors HL1 and HL3 showed enhanced activity compared with that of rosiglitazone. The complex VO(L-3)(2) showed the most efficacious hypoglycemic effects in this study; however, neither additive nor synergistic effects were observed using this acute animal model.

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