Structure-activity relationship and molecular action mechanism in the family of antidiabetic bis (picolinato )oxovanadium (IV) complexes

Trials for the use of vanadium in treating diabetes mellitus (DM) was reported in 1899, which was 23 years before Banting and Best discovered insulin and used it to treat diabetic patients. However, pharmaceutical interest in vanadium as an insulin substitute started in 1980. Ten years after, in 1990, orally active insulin substitutes were found as chelated oxovanadium(IV) complexes such as bis-(methylcysteinato)oxovanadium(IV) and bis(malonato)-oxovanadium(IV). Since these findings, a wide variety of antidiabetic oxovanadium(IV) complexes have been proposed. In 1995, bis(picolinato)oxovanadium(IV) complexes [VO(pa) 2 ] was found to have excellent in vitro insulinomimetic and in vivo antidiabetic activities in type 1-like diabetic rats. This VO(pa) 2 complex has an advantage to study structure-activity relationships in both in vitro and in vivo levels, and produce many interesting results. This article reviews the recent new progress in our research groups on the structure-activity relationship and the molecular action mechanism in the family of VO(pa) 2 complex.