Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry


Design of New Inhibitors of Dipeptidyl Peptidase-4 in Type 2 Diabetes by Computer Simulations

Author(s): Hicham Ayachi, Shirin Jamshidi, Meriem Merad, Yassine Bendiabdallah, Said Ghalem, Khondaker Miraz Rahman

The techniques of molecular modelling are widely used in chemistry, biology and the pharmaceutical industry. Most current drugs target enzymes. This theoretical approach allows us to predict the mode of interaction of a ligand with its receptor. Inhibition of Dipeptidyl Peptidase-4 “DPP-4” is an important approach in the treatment of disease in Type 2 diabetes. Several inhibitors have already been identified, but their affinity is insufficient to consider any of them being a pharmacological development. High-affinity inhibitors are used to inhibit DPP-4 as Linagliptin, Sitagliptin, Vildagliptin, Saxagliptin and Alogliptin but also as an adjuvant therapy for the treatment of Type 2 diabetes. It is for this purpose that molecular modelling techniques like docking and molecular dynamics have been developed. The results obtained in this work show the inhibition of DPP-4 by molecular modelling methods. The introduction of bulky groups causes a conformational rearrangement in the pocket of the active site that will probably be strengthened by the complementarity and therefore the activity increases. The results obtained in this study, by methods of molecular modelling which have been elucidated, allowed us to conclude that Linagliptin is a better inhibitor of DPP-4 than Sitagliptin, Vildagliptin, Saxagliptin and Alogliptin. Linagliptin has the potential to be the best inhibitor of DPP-4 in the treatment of Type 2 diabetes based on molecular modeling interaction.