α-Amylase and α-Glucosidase Enzyme Inhibition, Molecular Docking, and Pharmacokinetic Studies of Natural Products from Dilenia indica L. Barks

Abstract

Abstract The present study describes the isolation and structural elucidation of bioactive natural products from the hydro ethanol extract of Dilenia indica L. barks (DIHEEB) and their inhibitory activity against α-amylase and α-glucosidase enzymes. Some natural products including n-nonyl oleate (1), stigmasterol (2), β-sitotenone (3), betulin (4), and betulinic acid (5) were isolated from the DIHEEB extract. These natural products were characterized through IR, NMR, and mass spectroscopy. Among all these compounds, 4 and 5 have shown significant activity to inhibit α-glucosidase and α-amylase, which proves their anti-diabetic effect. The α-amylase and α-glucosidase inhibitory activity of 4 (α-amylase: IC50 68.79±1.6 μg/ml; α-glucosidase: IC50 69.19±1.8 μg/ml;) are very much comparable with known anti-diabetic drug acarbose (IC50 64.70±1.6 μg/ml). But compound 5 also shows a comparable extent of activity against α-amylase and α-glucosidase and it is also well established in the literature. Molecular docking and other in-silico properties were studied to elucidate the interactions and conformations of the isolated molecules with the target protein enzyme. With minimal conformational energy, 4 and 5 bind to the α-amylase (PDB ID: 4GQR) and α-glucosidase (PDB ID: 3A4A) enzymes, as proved by their respective docking score (-8.2 and -9.4 kcal/mol) and having different types of binding interactions. Also, the pharmacokinetics (PK), drug-likeness scores (DLS), and well permeability properties were studied along with no violation of Lipinski’s rule. Both in vitro and in silico results suggest that D. indica could be a potential source of anti-diabetic formulations. GRAPHICAL ABSTRACT