Discovery of Novel Triazole-Containing Pyrazole Ester Derivatives as Potential Antibacterial Agents

To develop new antibacterial agents, a series of novel triazole-containing pyrazole ester derivatives were designed and synthesized and their biological activities were evaluated as potential topoisomerase II inhibitors. Compound4dexhibited the most potent antibacterial activity with Minimum inhibitory concentration (MIC) alues of 4 µg/mL, 2 µg/mL, 4 µg/mL, and 0.5 µg/mL againstStaphylococcus aureus,Listeria monocytogenes,Escherichia coli, andSalmonella gallinarum, respectively. The in vivo enzyme inhibition assay4ddisplayed the most potent topoisomerase II (IC50= 13.5 µg/mL) and topoisomerase IV (IC50= 24.2 µg/mL) inhibitory activity. Molecular docking was performed to position compound4dinto the topoisomerase II active site to determine the probable binding conformation. In summary, compound4dmay serve as potential topoisomerase II inhibitor.Keywords:pyrazole;triazole;ester;antibacterial;topoisomerase II inhibitor