Modifying Antibiotic Activity of Synthetic Thiadiazine Analogs Against MDR Bacteria and ADMET Analysis

The indiscriminate use of antibiotics has led to the selection of resistant bacterial strains, significantly reducing the effectiveness of conventional treatments. In this context, thiadiazines have emerged as promising agents due to their antioxidant and antibacterial properties. This article aims to evaluate the antibacterial potential of synthetic thiadiazine analogs against selected bacterial strains. The synthesized compounds are purified using high-performance liquid chromatography, and absorption, distribution, metabolism, excretion, and toxicity analyses are performed, including interaction profiling with over 370,000 bioactive compounds. The bacterial strains Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 are used as test organisms. When combined with standard antibiotics, thiadiazine compounds significantly reduced the minimum inhibitory concentration. However, some analogs exhibited antagonistic effects, particularly against gentamicin and erythromycin. Direct antibacterial activity is limited, with compounds IJ26 and IJ28 showing the most notable effects. These findings suggest that thiadiazine analogs may potentiate antibiotic activity, although further studies are needed to fully understand their biological interactions and mechanisms of action.