Molecular Docking Study of Active Compounds of Ketapang Leaves (Terminalia Catappa L.) Against Inhibitors Maltase Glucoamylase And Modification of New Compounds

Abstract

The prevalence of diabetes mellitus is projected to reach 853 million by 2050. Postprandial hyperglycemia induced by the maltase glucoamylase enzyme can exacerbate the condition of diabetic patients. Although acarbose is widely used, it causes gastrointestinal side effects; thus, natural alternatives like ketapang leaves (Terminalia catappa L.) serve as a potential source of antidiabetic active compounds. This study aimed to evaluate the binding affinity, root mean square deviation (RMSD) values, and amino acid interactions of 70 active compounds from ketapang leaves against the maltase-glucoamylase enzyme using a molecular docking approach, alongside designing a novel potential compound modification as an antidiabetic drug candidate. In silico docking simulations were performed using PyRx-AutoDock Vina, structural optimization via VegaZZ, method validation using PyMOL, visualization through Discovery Studio Visualizer, and 2D/3D structural preparation using ChemDraw. The docking results of the 70 test compounds revealed that 41 compounds exhibited ΔGBinding values ranging from -6.3 to -8.5 kcal/mol, 66 compounds showed RMSD values ≤ 2Å, and 5 compounds shared similar amino acid residue interactions with the positive control, acarbose. Structural modification of gallic acid 3-O-(6-galloylglucoside) yielded a novel compound, 4-hydroxy-3-(2-hydroxyethoxy)-5-methoxybenzoic acid, which demonstrated a ΔGBinding value of -5.5 kcal/mol, an RMSD of 1.673 Å, and a matching amino acid residue interaction with the positive control at ASP A:649. In conclusion, active compounds from ketapang leaves and the newly modified compound show promising potential as maltase-glucoamylase enzyme inhibitors via molecular docking.