Modélisations des interactions dipeptidyl peptidase 4– inhibiteurs à l’aide de technique de docking moléculaire.

Abstract

Type 2 diabetes is a chronic and painless disease. It is characterized by excessive high blood sugar levels. This accumulation of blood results from a disturbance in the absorption, use and storage of sugars provided by food. In our work, we focused on how to treat type 2 diabetes by inhibiting dipeptidyl peptidase 4 which is an enzyme used in decomposition of encritins, it strengthens the effect of glucose on insulin secretion and improves blood sugar control in diabetic patients.To carry out this work, we use the molecular modeling methods and more specifically the molecular docking approach by Surflex-dock software, it has been shown to be effective enough to reproduce the experimental test since 72.50% of RMSD values are less than 2Å. According to visual analysis, we were able to confirm the program's performance. This method was used to study the interaction mode of dipetidyl peptidase 4-inhibitor complexes and to detect in silico new and more effective inhibitors. In this study we highlighted the compounds CID 145676316 and CID 68023157 as new antidiabetic agents with more affinities compared to previously known agent. Finally, we predicted the physical, chemical and kinetic properties and also verified the toxicity of these new proposed compounds