Glyco-conjugated thiosemicarbazones of substituted isatin containing D-galactose moiety: Synthesis, bacterial/fungal inhibition assay and molecular docking study

Abstract Some different isatin-thiosemicarbazones 4a-4h derived from corresponding substituted isatins and N-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)thiosemicarbazide have been synthesized and studied for antibacterial and antifungal activity. Inhibitory activities of some better active compounds against several S. aureus enzymes, including two enzymes of bacterial topoisomerase type II, DNA gyrase and DNA topoisomerase IV (Topo IV), have also been determined. The obtained results showed that the potential compounds 4c, 4d, and 4e all exhibited remarkable activity on antimicrobial tests for five Gram-(+) and four Gram-(−) bacterial strains as well as five fungal strains. These most potent compounds were further studied induced fit docking and MM-GBSA researches. The obtained results indicated that H-binding interactions with residue Arg1122 on chain B, as well as stacking π-π interactions with residues DG10 and DC11 on chain E were important interactions, perhaps determining the high bioactivity of compound 4c. The 280 ns-MD simulation showed all the dynamic interactions that took place between inhibitor 4c and residues in active pocket of enzyme 2XCS during the period when it entered and settled in this pocket as well as its stability in receptor in order to induce the necessary biological reaction (i.e., the inhibitory activity of this enzyme of S. aureus).