Coumarin-Triazole-Thiazole hybrids: A new avenue in Antitubercular agents

The present work reports the design and synthesis of a series of 2-(4-(((2-oxo-2H-chromen-4-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(thiazol-2-yl)acetamide derivatives (4a-4k), which were investigated for their potential against tubercular activities. The well-known click cycloaddition reaction of azido derivatives (3a-3k) and 4-(prop-2-yn-1-yloxy)-2H-chromen-2-one (2) in the presence of catalytic amount of CuSO₄ in H₂O and DMF was employed. Notably, compounds 4c, 4d, and 4g showed the most promising results with MIC values against tuberculosis are 7.81 μg/mL, 2.61 μg/mL, and 7.81 μg/mL, respectively. Compounds (4a-4k) exhibited moderate to excellent antioxidant activities and low cytotoxicities. In addition, molecular docking studies were performed to investigate the binding interaction modes of the compounds (4a-4k) with various proteins and ligand sites.