Synthesis, characterization, biomolecular interaction and in vitro glucose metabolism studies of dioxidovanadium(V) benzimidazole compounds

Abstract

We have previously reported that the metal-based anti-diabetic drug candidates, cis-[VO2(obz)py] (1) (Hobz = 2-hydroxyphenyl-1H-benzimidazole and py = pyridine) and cis-[VO2(Hpybz)(pybz)] (2) (Hpybz = 2-pyridyl-1H-benzimidazole) illustrated hypoglycaemic activities both in vitro and in vivo, respectively. Herein, we report the biomolecular interaction studies of 1 and 2 as well as their new analogues: cis-[VO2(Hmpybz)(mpybz)] (3) (Hmpybz = 2-(4-methyl-2-pyridyl-1H-benzimidazole) and cis-[VO2(mobz)py] (4) (Hombz = 2-(5–6 dimethyl-2-pyridine)-1H-benzimidazole) towards Bovine Serum Albumin (BSA) and Protein Phosphatase Tyrosine (PTP)-1B enzyme, respectively. The new metal complexes 3 and 4 were characterized with the aid of various characterization techniques and their structures were confirmed by single crystal X-ray crystallography and elemental analysis. Unique concentration-dependent PTP-1B inhibitory activities of 2 and 3 were observed under pre- and post-lysis experimental conditions. Lactate assays showed that 2 and 3 reduces the rate of lactate production. As there is a linear relationship between lactate levels and insulin resistance, this suggests that compounds 2 and 3 are able to alleviate this phenotype via the reduction of lactate build-up in HEK293T cells. The glucose consumption rate was insignificantly altered in response to 2 and 3, suggesting that these compounds do not affect glucose uptake in HEK293T cells.