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

The rational design of novel thiazolo[2,3- c ][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 M. tuberculosis and M. bovis strains. Among the synthesized compounds, five compounds, 10 , 11 , 35 , 37 and 38 , revealed antimicrobial activity, albeit with differential potency against various microbial strains. Compounds 10 and 37 were the most active against S. mutans (MIC: 8 μg/mL), while compounds 11 and 37 showed the highest activity against B. subtillis (MIC: 16 μg/mL), whereas compounds 10 , 11 and 37 displayed activities against E. coli (MIC: 16 μg/mL). Meanwhile, compounds 10 and 35 depicted activities against S. typhi (MIC: 16 μg/mL) and compound 10 showed antifungal activity against C. albicans (MIC: 32 μg/mL). The current study has identified two broad-spectrum antibacterial hit compounds ( 10 and 37 ). Further structural investigation on these molecules is underway to enhance their potency.