Physicochemical, ADMET, and Molecular Dynamics Simulations against Bacillus subtilis HmoB for Antibacterial Potentiality of Methyl 𝜶-D-glucopyranoside Derivatives

Abstract

Monosaccharide derivatives are important in the field of biological chemistry because of their effectiveness against bacterial pathogens, as well as to synthesize biologically active products. Designing novel antibacterial agents with new structural scaffolds that combat drug-resistant pathogens is an urgent task. Therefore, the present study targets to identify the binding affinity of a series of previously synthesized methyl α-D-glucopyranoside (MDGP) derivatives with molecular docking and molecular dynamics along with their physicochemical and pharmacokinetic properties. The density functional theory (DFT) calculations were executed for the MDGP derivatives using B3LYP/3–21G, which was also used for the illustration of partial atomic charge and molecular electrostatic potential (MEP). The designed derivatives were evaluated for their antimicrobial activities through a molecular docking study with Bacillus subtilis HmoB heme oxygenase by AutoDock. The binding affinity from molecular docking score for Derivatives 8–10 (–10.11, –10.41, and –12.20 kcal/mol) against the bacterial pathogen B. subtilis HmoB gives the evidence for being potential antimicrobial agents. Furthermore, a 100-ns molecular dynamics simulation study revealed the stable conformation and binding pattern of MDGP derivatives in a stimulating environment. In addition, in silico ADMET study, toxicity and bioactivity parameters were calculated for MDGP and its derivatives for evaluating their safe uses and predicting the pre-study of clinical phases as drug molecules by using software and an online database. Our designed new MDGP derivatives might be exhibited as first-rate and superior pharmacological profiles in medicinal chemistry, which may give the leading information for further studies about their biological activity.