Evaluating Efflux Pump Inhibition in Staphylococcus aureus 1199B Strain Using Thiadiazine-Derived Compounds: In Vitro and In Silico Approaches.

Thiadiazines are heterocyclic compounds known for some pharmacological activities. However, the ability of these compounds and their derivatives to act as antibacterial agents and inhibitors of the efflux system in resistant bacteria remains unknown. This study aims to evaluate the antibacterial and NorA efflux pump inhibitory activities of thiadiazine-derived compounds (IJ14, IJ15, IJ16, IJ17, IJ18, IJ19, and IJ20) against the Staphylococcus aureus 1199B strain. Minimum Inhibitory Concentration (MIC) tests and antibacterial activity assessment through NorA efflux system inhibition were performed using microdilution assays in 96-well plates. Additionally, ethidium bromide (EtBr) fluorescence emission assays were conducted to evaluate efflux system inhibition. The methodology revealed that the IJ17 and IJ20 compounds presented MIC values of 256 and 597.3 μg/mL, respectively. The efflux pump inhibition assessment using the microdilution method showed significant results for all compounds, which also increased the fluorescence rates emitted by EtBr. Consequently, thiadiazine-derived compounds exhibit promising results in targeting a key bacterial resistance mechanism, underscoring the need for further studies, such as molecular tests, to evaluate their mechanism of action and clarify the feasibility and efficacy of these compounds as antibacterial agents.