In Silico Study of Mangostin Compounds and Its Derivatives as Inhibitors of α-Glucosidase Enzymes for Anti-Diabetic Studies

SIMPLE SUMMARY: Diabetes is often treated with drugs, such as acarbose, metformin, and sulfonylurea. These drugs can cause various side effects such as stomach upset and gastrointestinal symptoms. Therefore, natural compounds and their derivatives, such as mangostin, are the best alternatives to these drugs. In silico potential antidiabetic tests can be performed as an initial analysis to determine which compound offers the best result. Available methods include molecular docking and molecular dynamics simulations. Based on these results, γ-mangostin had the best potential among the compounds. Therefore, it can be used to prepare better derivatives to replace acarbose as an antidiabetic drug. ABSTRACT: Diabetes is a chronic disease with a high mortality rate worldwide and can cause other diseases such as kidney damage, narrowing of blood vessels, and heart disease. The concomitant use of drugs such as metformin, sulfonylurea, miglitol, and acarbose may cause side effects with long-term administration. Therefore, natural ingredients are the best choice, considering that their long-term side effects are not significant. One of the compounds that can be used as a candidate antidiabetic is mangostin; however, information on the molecular mechanism needs to be further analyzed through molecular docking, simulating molecular dynamics, and testing the in silico antidiabetic potential. This study focused on modeling the protein structure, molecular docking, and molecular dynamics simulations and analyses. This process produces RMSD values, free energies, and intermolecular hydrogen bonding. Based on the analysis results, all molecular dynamics simulations can occur under physiological conditions, and γ-mangostin is the best among the test compounds.