Vanadium metal complexes' inhibition studies on enzyme PTP‐1B and antidiabetic activity studies on Wistar rats

Evidence from biochemical, genetic, and pharmacological studies strongly suggest that inhibition of protein tyrosine phosphatase‐1B (PTP‐1B) enzyme could address both diabetes and obesity and thus making PTP‐1B as an exciting target for drug development. Although many natural PTP‐1B inhibitors showed promising clinical and potential activity, still there is no clinically used PTP‐1B inhibitor which is most likely due to relatively low activities or lack of selectivity. With this background, we have synthesized and characterized the inhibitors exclusive for PTP‐1B. Vanadium metal complexes were our choice. The purpose of this investigation is twofold: firstly, to evaluate the inhibitory properties of these vanadium metal complexes on enzyme PTP‐1B and secondly, to know the ease with which these metal complexes are being transported by transporting proteins like bovine serum albumin (BSA). To synchronize these results, experiments on induced diabetic Wistar Rats were conducted. Also, we evaluated the PTP‐1B inhibitory effects of these vanadium metal complexes theoretically (molecular modeling) and experimentally (enzyme kinetics) and found that they have excellent inhibitory properties on PTP‐1B. These complexes upon injecting reduced the serum glucose levels to normal range in induced diabetic Wistar rats within 3 days of experiments. The order of glucose reducing properties of these metal complexes from different experiments is found to be the same. Among these complexes, [7‐imi], which is derived from [Bis(1,3‐diphenyl‐1,3propanedione)oxovanadium (IV)] and imidazole as ligands, has shown to be more effective in in vitro and in vivo studies compared with methyl imidazole and ethyl imidazole.