Synthesis, Antimicrobial, Molecular Docking Against Bacterial and Fungal Proteins and In Silico Studies of Glucopyranoside Derivatives as Potent Antimicrobial Agents.

Carbohydrate derivatives play a crucial roles in biochemical and medicinal research, especially in the fields of chemistry and biochemistry. From this perspective, the present study was designed to explore the synthesis of methyl α-D-glucopyranoside derivatives (1-8), focusing on their efficacy against bacterial and fungal inhibition. The structure of the synthesized compounds was ascertained using FTIR, H-NMR, C-NMR, mass and elemental analyses. Antimicrobial screening revealed strong antifungal properties, with compound 7 exhibiting minimum inhibitory concentrations (MICs) ranging from 16-32 μg/L and minimum bactericidal concentrations (MBCs) ranging from 64-128 μg/L. Incorporating decanoyl acyl groups at C-2 and C-3 of (7) significantly improved the efficacy against bacteria and fungi. Structure-activity relationship (SAR) analysis indicated that adding nonanoyl and decanoyl groups to the ribose moiety enhanced potency against both bacterial and fungal strains. Computational methods, including molecular docking, density functional theory (DFT), Petra, Osiris, Molinspiration (POM) evaluation, and molecular dynamics (MD) simulations, were used to assess the efficacy of these derivatives. Compounds 6 and 7, which presented nonanoyl and decanoyl substituents, demonstrated greater efficacy. In addition, DFT studies identified compound 8 as possessing ideal electronic properties. Molecular docking revealed that compound 8 exhibits exceptional binding affinities to bacterial proteins, conferring potent antibacterial and antifungal activities. In addition, pharmacokinetic optimization via POM analysis highlighted compounds 1 and 2 as promising bioavailable drugs with minimal toxicity. Molecular dynamics simulations confirmed the stability of the 2-S. aureus complex, revealing the therapeutic potential of compounds 2 and 8. Future experiments are required to validate their efficacy for pharmaceutical development. The integration of in vitro and in silico methods, including DFT anchoring dynamics and molecular dynamics simulations, provides a solid framework for the advancement of effective anti-infective drugs.