Title : Synthesis, ADMET, PASS, molecular docking, and dynamics simulation investigation of novel octanoyl glucoopyranosides and valeroyl ribofuranoside esters.
Abstract:
The rising threat of microbial resistance necessitates the continuous search for novel bioactive compounds. In this study, we synthesized and characterized two novel acylated monosaccharide derivatives—compound 2 (Methyl 4,6-O-benzylidene-2,3-di-O-octanoyl-α-D-glucopyranoside) and compound 4 (Methyl-2,3-O-isopropylidene-5-O-valeroyl-β-D-ribofuranoside)—with potential antifungal and antibacterial properties. The synthetic route utilized direct acylation under mild conditions to ensure high selectivity and yield. Comprehensive in silico analyses, including ADMET profiling, PASS predictions, molecular docking, and 100 ns molecular dynamics (MD) simulations, were conducted. Notably, compound 2 exhibited a binding affinity of −8.71 kcal/mol with lanosterol 14α-demethylase (PDB: 3LD6), while compound 4 showed favorable binding with dihydrofolate reductase (PDB: 3ZMI). Both compounds demonstrated stable protein-ligand interactions supported by RMSD, RMSF, SASA, and radius of gyration (Rg) analyses. MM-GBSA calculations revealed strong binding free energies (ΔG_bind ≈ −81.36 and −46.65 kcal/mol). These findings underscore the therapeutic potential of biodegradable, non-azole sugar esters as next-generation antifungal agents.
