Integrated Protocol to Design Potential Inhibitors of Dipeptidyl Peptidase-4 (DPP-4)

Background: A strategy for the treatment of type II diabetes mellitus is the inhibition of the enzyme known as dipeptidyl peptidase-4 (DPP-4). Aims: This study aims to investigate the main interactions between DPP-4 and a set of inhibitors, as well as proposing potential candidates to inhibit this enzyme. Methods: We performed molecular docking studies followed by the construction and validation of CoMFA and CoMSIA models. The information provided from these models was used to aid in the search for new candidates to inhibit DPP-4 and the design of new bioactive ligands from structural modifications in the most active molecule of the studied series. Results: We were able to propose a set of analogues with biological activity predicted by the CoMFA and CoMSIA models, suggesting that our protocol can be used to guide the design of new DPP-4 inhibitors as drug candidates to treat diabetes. Conclusion: Once the integration of the techniques mentioned in this article was effective, our strategy can be applied to design possible new DPP-4 inhibitors as candidates to treat diabetes.