ADMET Analysis, Antibacterial and Modified Antibiotic Activities of Thiadiazine Derivatives

Background: Infections caused by multi-resistant microorganisms are a public health issue. Synthetic products have been studied as a therapeutic alternative for these cases, with the aim of antibacterial activity or enhancing existing antibiotics.Methods: This study aimed to evaluate the antibacterial activity upon modifying antibiotic actions and to perform a pharmacokinetic analysis of compounds derived from thiadiazine. The products were synthesised, and a chemical analysis was performed using thin-layer chromatography (TLC).Results: After obtaining the compounds, minimum inhibitory concentration (MIC) and modified antibiotic activity tests were performed, in which norfloxacin and gentamicin antibiotics were used against multidrug-resistant (MDR) bacterial strains of Staphylococcus aureus 10 (S. aureus 10) and Pseudomonas aeruginosa 24 (P. aeruginosa 24) using the microdilution method. We also performed topological analyses, a similarity evaluation with drugs, and in-silico absorption, distribution, metabolism, excretion and toxicity (ADMET) analyses. Only two compounds showed antibacterial activity against the examined strains. However, all compounds showed activity against the S. aureus strain when associated with norfloxacin. The in-silico analysis showed that the compounds have high lipophilicity and non-toxic characteristics. Conclusions: Therefore, the thiadiazine-derived compounds potentiate the antibiotic activity against S. aureus 10 bacteria and have ADMET properties, which are favourable for further studies on these compounds as potential low-toxicity sources for the MDR bacteria problem.