Development of Potent Antimicrobial Isatin-Sulphonamide Derivatives: In Vitro and In Silico Studies

Objective: The rapid emergence of multidrug-resistant bacteria poses a serious threat to public health, highlighting an urgent need for the development of novel and potent antimicrobial agents. Antibiotic resistance is primarily driven by the overuse and misuse of antibiotics, which in many countries remain readily available without prescription. Methods: In this study, a novel series of isatin derivatives was designed and synthesized via a condensation reaction to form Schiff bases. The structures of all synthesized compounds were confirmed using various analytical techniques, including 1H and 13C NMR spectroscopy and ESI mass spectrometry. The synthesized compounds were evaluated for their in vitro antimicrobial activity against Escherichia coli, Klebsiella pneumoniae, Salmonella Typhi, Staphylococcus aureus, and Bacillus subtilis. Results and Discussion: Among the tested compounds, SP2 exhibited the most potent antimicrobial properties, demonstrating a considerable zone of inhibition and a low minimum inhibitory concentration (MIC) against both Gram-positive and Gram-negative strains. In the DPPH radical scavenging assay, compound SP2 also showed the highest antioxidant activity, with an IC50 value of 39.29 µg/mL. In silico molecular docking studies corroborated these findings, as compound SP2 displayed the highest binding affinity, with a docking score of –9.9 kcal/mol toward the target protein (PDB ID: 1G2A). Conclusions: In summary, isatin-sulphonamide hybrid SP2 demonstrated significant antioxidant activity (69.41% inhibition at 100 µg/mL; IC50: 39.29 µg/mL), notable antimicrobial efficacy (MIC: 0.88–1.05 µmol/mL; zone of inhibition: 22–25 mm), and a strong binding affinity of –9.9 kcal/mol, which is comparable to that of the reference molecule.