Molecular docking and molecular dynamics studies of bioactive compounds contained in noni fruit (Morinda citrifolia L.) against human pancreatic α-amylase

Human pancreatic α-amylase inhibition is currently a promising therapeutic target against type 2 diabetes (DMT2) because it can reduce aggressive digestion of carbohydrates into absorbable monosaccharides. In Indonesia, medicinal plants, e.g. Morinda citrifolia fruit, have been empirically utilized as a blood-sugar reducer, however, the inhibitory activity of compounds in this plant against human pancreatic α-amylase is still limited or none. Therefore, this study aimed to test the interaction of 7 compounds (americanin, asperulosidic acid, damnacanthal, quercetin, rutin, scopoletin, and ursolic acid) contained in noni fruit against human pancreatic α-amylase by molecular docking and molecular dynamics and compared their binding modes with that of acarbose. Results of the molecular docking simulation indicated that the ursolic acid compound possesses the best binding energy (-8.58 kcal/mol) and comparable to that of acarbose (-8.59 kcal/mol). The molecular dynamics study at 100 ns simulation, the values of RMSD, RMSF, the radius of gyration (Rg), the solvent-accessible surface area (SASA), principal component analysis (PCA), and MM-PBSA binding free energy were stable and identical to those of acarbose. It could be concluded that ursolic acid might be potential in inhibiting human pancreatic α-amylase, thus, potential to be developed as an anti-DMT2 drug candidate. Communicated by Ramaswamy H. Sarma