Euonymus laxiflorus Champ. Bioactive Compounds Inhibited α-Glucosidase and Protein Phosphatase 1B – A Computational Approach Towards the Discovery of Antidiabetic Drugs

Abstract

Euonymus laxiflorus Champ. has recently proven for its antidiabetic potential yet its ingredientactivity relationship is vastly unknown. A combination of quantum calculation, molecular docking simulation, physicochemical analysis, and ADMET was utilised together for the theoretical argument on potentiality of bioactively undetermined components (1-15) against α-glucosidase (PDB-3W37) and tyrosine phosphatase 1B (UniProtKB-PTP1B). Dipole moment values indicate the favoured bio-medium compatibility of 10 (6.370 Debye), 12 (6.381 Debye), and 15 (8.446 Debye), while the values discourage the potential of 5 (0.792 Debye) and 11 (0.905 Debye). Molecular electrostatic potential maps imply the intermolecular interacting flexibility of 6-10 and 12-15. Docking-based simulation predicts the most effective inhibitory systems, i.e. (i) ligand- 3W37: 10 ≈ 11 (DS -11.7 kcal.mol-1) ≈ 3 (DS -11.6 kcal.mol-1) > 7 ≈ 12 (DS -11.1 kcal.mol-1); (ii) ligand-PTP1B: 11 (DS -12.0 kcal.mol-1) > 13 (DS -11.8 kcal.mol-1) > 5 (DS -11.2 kcal.mol-1) > 3 (DS -11.0 kcal.mol-1). Polarisability justifies the bio-medium compatibility of 10 (70.8 Å3) and 15 (64.7 Å3) while especially opposes the potentiality of 11 (19.1 Å3). Physicochemical and pharmacological properties support the suitability for further drug-like development. Altogether, 10 (7-Hydroxy-6,7-dihydro-cis/trans-geraniate, 3-O-α-L-arabinopyranosyl (1→6)-β-Dglucupyranosyl) and 15 (3,5-dimethoxy-4-hydroxyphenol)-1-O-β-D-(6'-O-galloyl)- glucopyranoside) are allocated as the most promising antidiabetic inhibitors.