Novel benzylidene derivatives: Synthesis and their antimicrobial and anticancer studies and in silico investigations

• Highly effective derivatives of methyl 4,6- O -benzylidene-α-D-glucopyranoside (MBDG) have been developed and synthesized. • Compounds 4 and 7 exhibited strong antibacterial activity against B. subtilis and antifungal activity against A. niger and Aspergillus flavus. • The heptanoyl derivative, compound 6 , showed promising anticancer activity • Compounds 4 and 5 exhibited tight binding with the bacterial protein on Bacillus subtilis and the targeted fungal protein on Aspergillus niger. • Molecular dynamics simulations showed that the ligand‒protein complexes ( 3 and 4 ) were stable. The average binding free energy for MM-PBSA analysis was greater, indicating an efficient binding process. • ADMET predictions revealed favorable pharmacological profiles for compounds 4 and 5 . Given the importance of carbohydrate-based drugs, this study focused on the synthesis of five novel analogs ( 3–7 ) of methyl 4,6 -O- benzylidene-α-D-glucopyranoside ( 2 , MBDG). In vitro antimicrobial screening revealed that these MBDG derivatives possess promising antifungal activity against Aspergillus niger and moderate antibacterial activity. Compound 4 exhibited an MIC of 0.68–2.7 mg/mL and an MBC of 1.35–5.4 mg/mL against five different bacterial strains. The insertion of various acyl groups, particularly (CH 3 (CH 2 ) 3 CO-) and (CH 3 (CH 2 ) 4 CO-) at the second and third positions of MBDG ( 2 ), increased the antimicrobial effectiveness. Compound 6 was found to reduce EAC (Ehrlich ascites carcinoma) cell proliferation by 30.17% at 500 μg/mL, with an IC 50 value of 852.47 μg/mL. Furthermore, frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) analyses were conducted to investigate the physicochemical properties and relative reactivities of the newly synthesized MBDGs. Molecular docking analysis revealed that compounds 4 and 5 bind efficiently with binding affinities of -7.2 kcal/moL and -5.7 kcal/moL against Bacillus subtilis and A. niger , respectively, compared with the standard drug azithromycin. The stability of the protein‒ligand complexes were ascertained via MMPBSA binding free energy calculations and molecular dynamics (MD) simulations. These findings demonstrate that compounds 4 and 5 may be useful antimicrobial medications. An in silico ADMET assay was employed to evaluate the pharmacological and toxicological properties of the MBDGs.