Synthesis and characterization of oxidovanadium complexes as enzyme inhibitors targeting dipeptidyl peptidase IV

Two oxidovanadium(IV) complexes carrying Schiff base ligands obtained from the condensation of 4,5-dichlorobenzene-1,2-diamine and salicylaldehyde derivatives were synthesised and characterised, including their X-ray crystallographic structures. They were evaluated as dipeptidyl peptidase IV (DPP-IV) inhibitors for the treatment of type 2 diabetes. These compounds were moderate inhibitors of DPP-IV, with IC50 values of ca. 40μM. In vivo tests showed that complexes 1 and 2 could lower significantly the level of glucose in the blood of alloxan-diabetic mice at doses of 22.5mgV·kg−1 and 29.6mgV·kg−1, respectively. Moreover, molecular modeling studies suggested that the oxidovanadium complexes 1 and 2 could fit well into the active-site cleft of the kinase domain of DPP-IV. To the best of our knowledge, this is the first report of vanadium complexes capable of inhibiting DPP-IV. Synopsys: Two newly synthesised oxidovanadium(IV) complexes are capable of inhibiting moderately the activity of dipeptidyl peptidase IV (DPP IV) in vitro. These are the first examples of vanadium complexes able to target DPP IV in vitro. [Display omitted] •X-ray structures of two new oxovanadium(IV) Schiff–base complexes determined•Complexes inhibit dipeptidyl peptidase IV (DPP-IV), potential type 2 diabetes target.•Molecular docking suggests good fit for active-site of kinase domain of DPP-IV.•First example of vanadium complexes able to inhibit DPP IV in vitro.