Thermochemical, Molecular Docking and ADMET Studies of Some Methyl α-D-Glucopyranoside Derivatives

In this study, methyl α-D-glucopyranoside and its modified derivatives were optimized by employing density functional theory (DFT) with B3LYP/3-21G level theory to explore their structural and thermodynamic properties. Electronic energies, enthalpies, Gibbs free energies, dipole moments, Highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gaps, the density of states (DOS) and molecular electrostatic potential (MEP) of these modified compounds were found optimal in the subsequent analysis. Molecular docking has been performed against potential inhibitors of the Bacillus subtilis Obg protein (PDB: 1LNZ) to search the binding affinity and mode(s) of six compounds that have significant antibacterial and antifungal activities. It was found that the selected glucopyranoside derivatives have strong interactions mainly with Arg236 and Arg238 residues of the Bacillus subtilis Obg protein, and the molecules were surrounded by other active site residues like Lys156, Pro91, and Glu333. An absorption, distribution, metabolism, excretion, and toxicity (ADMET) calculation reveals that the modified derivatives are less toxic and have improved pharmacokinetic features over the parent drug. This computational investigation showed that these methyl α-D-glucopyranoside derivatives might be used as potential inhibitors against the promising antibacterial and antifungal activities for future studies. The Chittagong Univ. J. Sci. 42(1): 58-83, 2020