Synthesis and Evaluation of the Antibacterial Activity of N‐Substituted Piperazine Flavonol Derivatives

ABSTRACT Diseases resulting from bacterial invasion have consistently posed a substantial threat to public health and safety. To address this problem, this study aimed to discover novel chemical structures with antibacterial activity by using flavonols as lead compounds. Through structural modifications, we introduced various N ‐substituted piperazine compounds to synthesize ten previously unreported compounds. Subsequently, the antibacterial activities of these compounds against Staphylococcus aureus and Escherichia coli were evaluated. Compound 2 g was identified as the most potent compound, exhibiting minimum inhibitory concentration (MIC) values of 6.25 µg/mL against S. aureus and 25 µg/mL against E. coli . Additionally, compound 2g effectively inhibited the growth of S. aureus and E. coli , with inhibition zones measuring 16 mm and 15 mm, respectively. At a concentration of 8 × MIC, the bacterial counts of both strains were reduced by 1.75 and 0.72 logCFU/mL within 60 min. Furthermore, compound 2g significantly inhibited the formation of S. aureus biofilms. Molecular docking studies suggested that the staphylococcal accessory regulator might be its potential target. This study provides valuable insights into the antibacterial activity of flavonoids and offers a scientific foundation for the development of novel antibacterial agents.