Study of the molecular interactions between DPP-IV and some inhibitors used for the treatment of type II diabetes mellitus

Type II diabetes mellitus is a metabolic disorder that involves a fai lure in the secretion and I or action of insulin in the body.1 One of the strategies involved in its treatment is the inhibition of DPP-IV, being interesting the analysis of the interactions between this enzyme and bioactive compounds of interest, using the technique known as molecular docking. In this work, 7 derivatives of omarigliptin2·3 were docked at the binding site of DPP-IV using GOLD4 program and the possible interactions were analyzed, considering the following parameters: (i) flexibilization of residues with basic character (e.g. Arg125); (ii) residues with acid character (Giu206); (iii) residues with polar character (Ser630, Tyr547 and Tyr666); (iv) two molecules of structural water; (v) and Goldscore as scoring function. Additionally, we evaluated the selected compounds with the BINANA5 tool (BINding ANAlyzer) to identify the main characteristics of the ligand-DPP-IV interactions observed. From the obtained results, it was observed that the interactions between the previously mentioned residues and nitrogen and fluoride atoms of the inhibitors are of the hydrogen bonding type, saline bridge and hydrophobic contacts at the active site of DPP-IV. In the case of the most active compounds there was also interaction with water molecules of the DPP-IV enzyme. Therefore, the resu lts obtained here can help the design of new candidates to inhibit DPP-IV.