Contribution à l’amélioration de l’activité biologique des inhibiteurs de la dipeptidyl-peptidase 4 dans le diabète de type 2 par simulation informatique.

Abstract

Type 2 diabetes mellitus (T2DM) is a severe and increasingly prevalent disease that is considered as a major global public health. It engenders about four millions death in the world.In our research, we focus on type 2 diabetes treatments based on inhibition of Dipeptidyl-peptidase 4 (DPP4). This enzyme cleaves the incritin hormones which help organism to regulate glycemia only in the case of hyperglycemia. The molecular modeling program: AutoDock, is used to develop in silico new potent DPP4 inhibitors. By poly-substitution of the inhibitor 356 in complex with DPP4 (PDB accession code:2RGU), the binding energy was increased from -11.13Kcal/Mol to -15.13 Kcal/Mol, by the introduction of NH2 on carbon 26, methyl on carbon 34 and finally, the replacement of methyl 14 by CH2CH2NH3+. The application of Lipinski rule informs us in a positive way about ADME/Tox properties of this compound that is considered as a potent DPP4 inhibitor.