Vanadyl−Thiazolidinedione Combination Agents for Diabetes Therapy

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]benzyl}thiazolidine-2,4-dione (HL¹), (±)-5-{4-[(5-hydroxy-1-methyl-4-oxo-1,4-dihydro-pyridin-2-ylmethyl)amino]benzyl}thiazolidine-2,4-dione (HL²), 5-[4-(5-hydroxy-4-oxo-4H-pyran-2-ylmethoxy)benzylidene]thiazolidine-2,4-dione (HL³), 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(L¹)₂, VO(L³)₂, and VO(L⁴)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(L³)₂ showed the most efficacious hypoglycemic effects in this study; however, neither additive nor synergistic effects were observed using this acute animal model.