In silico Identification of Fructose-1,6-biphosphatase Inhibitory Potentials of Xanthones Isolated from African Medicinal Plants: An Integrated Computational Approach

Abstract

Background: Type 2 diabetes mellitus continues to pose a threat to the existence of the human race. The increasing number of diabetic subjects can be effectively controlled by targeting enzymes responsible for high blood glucose levels. Xanthones are a class of phytochemicals that possesses promising pharmacological potentials. Objective: This study identified fructose 1,6-biphosphatase (FBPase) inhibitors by exploring xanthones isolated from African medicinal plants through ensemble docking, molecular dynamics simulation and density functional theory methods. Methods: The study used ensemble docking, molecular dynamics simulation and density functional theory (B3LYP/6-3G (d,p) basis set) and ADMET methods to select lead compound that may be effective as fructose-I,6-biphosphatase inhibitor. Results: The ensemble docking results identified globulixanthone C (-10.0 kcal/mol), 1-Isomangostin (- 9.0 kcal/mol), laurentixanthone A (-9.0 kcal/mol), bangangxanthone A (-8.9 kcal/mol) and staudtiixanthone B (-8.8 kcal/mol) as potential inhibitors of fructose-1,6-biphosphatase. Molecular dynamics studies showed the xanthones established good binding mode and their binding energy ranged from -74.057 to 53.669 kJ/mol. Also, the electronic and ADMET studies of the xanthones elucidated their excellent pharmacological potential. Conclusion: The study identified xanthones as potential fructose-1,6-biphosphatase inhibitors. The ligands' binding energy and MMPBSA calculations supported their possible inhibitory property. Also, the ADMET properties estimated show the ligands as suitable drug candidates as fructose-1,6-biphosphatase inhibitors. Further in vitro and in vivo investigation of the hit molecules is necessary to develop new FBPase inhibitors.