Molecular docking study on procyanidin derivatives as natural dipeptidyl peptidase-IV inhibitors in the treatment of Type 2 diabetes mellitus

Abstract

Background: Dipeptidyl peptidase IV (DPP-IV) is a multifunctional enzyme responsible for splitting the incretin hormone, which favors the release of insulin from the pancreatic beta cells. DPP-IV inhibitors prevent the degradation of incretins by the DPP-IV enzyme and are useful for the treatment of Type 2 diabetes. Procyanidins obtained from natural sources are polymers of catechin and epicatechin, which act as efficient intestinal DPP-IV inhibitors. Aims and Objectives: The study aimed to perform molecular docking of procyanidin and its derivatives with human DPP-IV to determine its binding efficacy and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Materials and Methods: The three-dimensional structure of human DPP IV was obtained from the RCSB - protein database. A total of 200 ligand derivatives of procyanidin were generated by the software ACD/ChemSketch. Initial quick docking (rough) was done using the software iGEMDOCK v2.0. The ones with the least binding energy were selected, and accurate docking was done in AutoDock 4.0 software. ADMET properties were analyzed using the Swiss ADME online tool. Results: Among the three ligands, 6-azido-2-(3, 4-dihydroxyphenyl)-4-[2-(3, 4-dihydroxyphenyl)-3, 5, 7-trihydroxy-3, 4-dihydro-2H-1-benzopyran-8-y1]-3, 4-dihydro-2H-1-benzopyran-3, 5, 7-triol has excellent binding energy with good ADMET properties. Conclusion: Using the molecular docking method in this study has led to the unveiling of a new natural DPP. IV inhibitor. This compound can be used as an effective drug candidate for treating type 2 diabetes mellitus.