Identification of potential DPP-4 inhibitors from Bryophyllum pinnatum by in-silico analysis

Abstract

Background: An estimated 463 million people already live with diabetes and that figure is set to rise to over 700 million by 2045, as per the International Diabetes Federation (IDF). The current form of treatment for Type-2 DM can be done with sulfonylureas, meglitinides, metformin, thiazolidinediones, incretin mimetics: Glucagon-like peptide 1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP), and amylin analogues (Pramlintide). Bryophyllum pinnatum (Lam.) Oken (B. pinnatum) belongs to the plant family crassulaceae used in traditional medicine in Asia. GLP-1 and Glucose-dependant Insulinotropic Polypeptide (GIP), both play a similar role in stimulating insulin secretion and are inactivated by dipeptidyl peptidase-4 (serine protease dipeptidyl peptidase-4) enzymes. Aims: To identify the potential anti-diabetic active compounds of Bryophyllum pinnatum against DPP-4 enzyme using in-silico methods. Methods and Material: The phytochemicals associated with Bryophyllum pinnatum were retrieved from ChEBI and canonical SMILES retrieved, followed by searching for its molecular properties and druglikeness using MolSoft LLC, toxicity test using ADVERPred, Swiss Target Prediction for predicting the DPP-4 inhibitors, molecular docking using Schrodinger software suite. Results: The in-silico study identified two phytochemicals from fourteen that have been predicted for DPP-4 inhibition potential against Type-2 DM. In CH₂CL₂ and CH₃OH solvent compounds 3,5-dihydroxybenzoic acid (-5.623 kcal/mol) and 3,4-didehydro-N4-deethylbrinzolamide (-4.91 kcal/mol) displayed the highest docking scores against human DPP-4 (5Y7K). Conclusions: The above-mentioned compounds revealed no side effects. The in-silico results strongly favour the beneficial use of phytochemicals from Bryophyllum pinnatum as a probable herb that can be used for adjuvant therapy. Further in-vitro and in-vivo tests are needed for confirmation.