Synthesis, characterization, molecular docking, dynamics simulation and pharmacokinetic evaluation of some novel monosaccharide esters

The development of carbohydrate-derived bioactive scaffolds with adjustable molecular and pharmacological properties is a key goal in medicinal and pharmaceutical chemistry. In this study, two novel acylated monosaccharide derivatives e.g., 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), were synthesized and characterized. Their antibacterial and antifungal properties were evaluated, revealing strain-dependent antimicrobial activity, though generally lower than reference agents. Compound 4 had the strongest antibacterial effect against Bacillus cereus , while compound 2 was more effective against Salmonella Typhi . Additionally, compound 2 exhibited the highest inhibition against Candida albicans , whereas compound 4 being most effective against Aspergillus niger . Molecular docking studies of synthesized esters against lanosterol 14α-demethylase (CYP51) and E. coli rhomboid protease GlpG showed that compound 2 had the most favorable docking score against CYP51 (−8.71 kcal/mol), while molecular dynamics simulations indicated stable behavior, supported by RMSD, RMSF, SASA, and radius of gyration (Rg) analyses. MM-GBSA calculations showed strong binding free energies (ΔG _bind ≈ −81.36 kcal/mol and −46.65 kcal/mol for compound 2 and 4 respectively). The molecular dynamics simulations confirmed the structural stability and favorable interactions of compound 2 with target proteins e.g., lanosterol-14α-demethylase (PDB: 3LD6). ADMET and PASS analyses indicated compound-specific pharmacokinetic and biological profiles, highlighting potential issues for further study. These results demonstrate structure-dependent relationships among molecular architecture, antimicrobial activity, target recognition, dynamic behavior, and pharmacokinetics, offering a foundation for optimizing monosaccharide-derived bioactive scaffolds.