Design and synthesis of novel substituted s-triazines tethered benzenesulfonamides as potential antimicrobial candidates: Antibiofilm and bacterial protein permeability assessments.

New s-triazine hydrazone hybrids (4a-4r) were designed and synthesized as promising microbial DNA gyrase inhibitors. This was done by taking the lead DNA gyrase inhibitor (AstraZeneca arylaminotriazine) as a reference. The novel samples were subsequently tested as antimicrobial agents against certain pathogenic bacteria and unicellular fungi. The antibiofilm potential and the membrane leakage test were used to determine the mechanism of the antimicrobial response. The minimum inhibitory concentration (MIC) values of 4g, 4i, and 4r samples were between 62.5 and 250.0 µg/mL. The MIC values for the 4g candidate against Staphylococcus aureus, Candida albicans, Enterobacter agglomerans, and Klebsiella pneumonia are 62.5, 125.0, and 250.0 µg/mL, respectively. Conversely, the MIC of compound 4i was 62.5 µg/mL for C. albicans and E. agglomerans and 125.0 µg/mL for S. aureus and K. pneumonia. Besides, a molecular docking study was performed to validate both the binding affinity and binding mode of the newly designed analogs of s-triazine candidates toward bacterial DNA gyrase receptors. The synthesized nanocomposites had promising antimicrobial potentials, which are encouraging their use in biomedical applications. Consequently, the afforded compounds can be employed as promising antimicrobial lead compounds for future optimization.