Facile Synthesis of N-(4-Bromo-3-methylphenyl)pyrazine-2-carboxamide Derivatives, Their Antibacterial Activities against Clinically Isolated XDR S. Typhi, Alkaline Phosphatase Inhibitor Activities, and Docking Studies

The emergence of extensively drug-resistant <i>Salmonella</i> Typhi (XDR-<i>S. Typhi</i>) poses a grave public health threat due to its resistance to fluoroquinolones and third-generation cephalosporins. This resistance significantly complicates treatment options, underscoring the urgent need for new therapeutic strategies. In this study, we synthesized pyrazine carboxamides (<b>3, 5a</b>-<b>5d</b>) in good yields through the Suzuki reaction. Afterward, we evaluate their antibacterial activities against XDR-<i>S. Typhi</i> via the agar well diffusion method; <b>5d</b> has the strongest antibacterial activity with MIC 6.25 (mg/mL). Moreover, in vitro Alkaline Phosphatase inhibitor activity was also determined; <b>5d</b> is the most potent compound, with an IC₅₀ of 1.469 ± 0.02 µM. Further, in silico studies were performed to find the type of interactions between synthesized compounds and target proteins.