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

Abstract

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.

Keywords: Dipeptidyl peptidase IV; Enzyme inhibitors; Molecular docking; Oxidovanadium (IV); Schiff base complexes.