Quantum Computational, Molecular Docking, Dynamics, PASS, and ADMET Analyses of Methyl α-D-Glucopyranoside Derivatives

Abstract

Novel antimicrobial and antifungal medicines are desperately needed, as evidenced by the increase in antibiotic resistance and other fungal diseases. Previously, we designed methyl α-D-glucopyranoside derivatives (2–8), which are essential for bacterial and fungal replication, in the context of ferulic acid decarboxylase inhibitors. The compounds tri-O-acyl and tri-O-p-bromophenyl derivatives were developed via the selective acylation of glucopyranoside. The compounds containing glucopyranoside derivatives showed remarkable antibacterial and antifungal efficacy when tested in silico against bacteria and fungi via PASS prediction. The compounds showed less toxicity, according to the cytotoxicity assessment. To clarify the mode of action, binding energies, and interaction characteristics of the synthesized compounds that target ferulic acid decarboxylase, extensive molecular docking experiments were conducted. To assess the absorption, distribution, metabolism, and toxicity of these substances, pharmacokinetic predictions were performed. The combination of pharmacokinetic and drug-likeness predictions has shown encouraging results. To summarize, the potential of these derivatives as candidates for the creation of novel antimicrobial drugs that target ferulic acid decarboxylase is highlighted by an integrated computational method that combines molecular docking, molecular dynamics simulation (MDS), ADMET assessment, and density functional theory (DFT) calculations.