Design, synthesis ADMET and molecular docking of new imidazo[4,5-b]pyridine-5-thione derivatives as potential tyrosyl-tRNA synthetase inhibitors.

In our effort of discovering new antimicrobial agents, a novel series of imidazo[4,5-b]pyridine-5-thione scaffolds were designed and synthesized and their chemical structures were characterized by physicochemical and spectral analysis. The synthesized compounds were assessed for their in vitro antimicrobial activities against pathogenic microorganisms. Results revealed that out the tested compounds, 3 exhibited the potent inhibitory effect (MIC = 0.49 μg/mL) as compared to the positive control, chloramphenicol (0.98 μg/mL) which predicted also to have the best pharmacokinetic and druglikness properties as well as lower toxicity profiles. Preliminary structure-activity relationships (SARs) study has been also investigated. Moreover, to understand the binding patterns of the tested compounds in the Staphylococcus aureus tyrosyl-tRNA synthetase active site, molecular docking study using the most active compound 3 was carried out. The obtained results indicate that analog 3 can potentially bound to the target enzyme with the highest docking score (-9.37 kcal/mol). Overall, our results showed that antimicrobial activity as well as ADMET and toxicity predictions were in consensus with the docking results.