Novel Schiff Base‐conjugated para‐Aminobenzenesulfonamide Indole Hybrids as Potentially Muti‐targeting Blockers against Staphylococcus aureus

Abstract Staphylococcus aureus ( S. aureus ) has developed strong resistance to a variety of clinical antibiotics, which makes the design and synthesis of novel structural molecules with outstanding antibacterial potential put on the agenda. The results of bioactivity assessment displayed that sulfonamide indole compound 4 h , which was modified with a butene group, had remarkable antibacterial activity against S. aureus (MIC=5 μM), and was superior to the reference drugs norfloxacin (MIC=13 μM) and sulfathiazole (MIC=501 μM). The propensity of evaluation of hybrid 4 h to induce drug resistance was lower than that of the reference drugs. In addition, the cytotoxicity assay revealed that compound 4 h had no obvious cytotoxicity to normal mammalian cells (RAW 264.7). Molecular docking analysis further demonstrated that the highly active molecule 4 h could interact with the active sites of DNA hexamer duplex and human carbonic anhydrase isozyme II through hydrogen bonds. Moreover, preliminary mechanistic studies indicated that hybrid 4 h prospectively acted as an blocker by disrupting the bacterial membrane of S. aureus and inserting itself into S. aureus DNA to prevent strains from replicating.