Evaluation of the Efflux Pump Inhibition Activity of Thiadiazine-Derived Compounds Against the <em>Staphylococcus aureus </em>1199B Strain

Substances with antibacterial properties have become crucial in light of the continuous increase in infections caused by multidrug-resistant bacteria. In this context, thiadiazines have emerged as heterocyclic compounds already known for their pharmacological activities. However, their potential as antibacterial agents and inhibitors of the efflux system found in resistant bacteria remains poorly understood. From this perspective, the present study highlights the synthesis of thiadiazine-derived compounds and evaluates their antibacterial activity and efflux pump inhibition against the Staphylococcus aureus 1199B strain. To this end, Minimum Inhibitory Concentration (MIC) tests were conducted, along with the analysis of antibacterial activity through the inhibition of the NorA efflux system using 96-well microdilution assays. Additionally, to assess efflux system inhibition, ethidium bromide (EtBr) fluorescence emission tests were performed, alongside in silico molecular docking studies. Based on the results obtained, it was observed that compound IJ28 exhibited direct activity against the tested SA 1199B strains, with an MIC of 512 µg/mL. It also demonstrated antibacterial activity through efflux pump inhibition, resulting in increased fluorescence rates emitted by EtBr. Compound IJ28 showed a more significant reduction in the Minimum Inhibitory Concentration (MIC) of ethidium bromide, decreasing from 26.6 µg/mL to 0.5 µg/mL, compared to the other compounds. Therefore, it is essential to conduct further studies to investigate the mechanism of action and clarify the feasibility and effects of compound IJ28 as a potential antibacterial agent.