Thiazolotriazoles As Anti-infectives: Design, Synthesis, Biological Evaluation and Studies.

The rational design of novel thiazolo[2,3-][1,2,4]triazole derivatives was carried out based on previously identified antitubercular hit molecule H127 for discovering potent compounds showing antimicrobial activity. The designed compounds were screened for their binding efficacies against the antibacterial drug target enoyl-[acyl-carrier-protein] reductase, followed by prediction of drug-likeness and ADME properties. The designed analogues were chemically synthesized, characterized by spectroscopic techniques, followed by evaluation of antimicrobial activity against bacterial and fungal strains, as well as antitubercular activity against and strains. Among the synthesized compounds, five compounds, , , , and , revealed antimicrobial activity, albeit with differential potency against various microbial strains. Compounds and were the most active against (MIC: 8 μg/mL), while compounds and showed the highest activity against (MIC: 16 μg/mL), whereas compounds , and displayed activities against (MIC: 16 μg/mL). Meanwhile, compounds and depicted activities against (MIC: 16 μg/mL) and compound showed antifungal activity against (MIC: 32 μg/mL). The current study has identified two broad-spectrum antibacterial hit compounds ( and ). Further structural investigation on these molecules is underway to enhance their potency.