4Bromobenzenesulfonate Schiff Base Derivatives Cause DNA Degradation in Bacterial Cells

Objective: The rise of multiantibioticresistant bacteria is directly linked to increased mortality from infectious diseases. There is an urgent medical need to address this issue by developing novel antibacterial agents with innovative and more potent mechanisms of action. Aryl sulfonates, structural analogs of the longused sulfonamide drugs, have also drawn significant pharmacological interest due to their fundamental biological properties, including antibacterial, antifungal, antiparasitic, antioxidant, antiviral, and antitumor activities. Methods: In line with our group’s ongoing focus on identifying cellular targets of antimicrobial agents, this study investigated 4bromobenzenesulfonate Schiff bases. First, the antibacterial activities of bis(4bromobenzenesulfonate) Schiff base derivatives were evaluated by determining minimum inhibitory concentrations (MICs). The compounds exhibited high activity against both Grampositive (Staphylococcus aureus, Bacillus subtilis) and Gramnegative (Escherichia coli, Pseudomonas aeruginosa) bacteria. Results and Discussion: The studied aryl sulfonate derivatives did not disrupt the bacterial cytoplasmic membrane but did alter the biochemical composition of the bacterial cells, as detected by FT-IR spectroscopy. Furthermore, UV–Vis absorption titration experiments demonstrated that these aryl sulfonate Schiff bases bind to DNA, and DNA laddering assays confirmed their damaging effect on DNA integrity. Conclusions: We propose that the primary mechanism of action of these aryl sulfonate Schiff bases against bacterial cells is DNA damage.