Facile Synthesis of <i>N</i>-(4-Bromo-3-methylphenyl)pyrazine-2-carboxamide Derivatives, Their Antibacterial Activities against Clinically Isolated XDR <i>S. Typhi</i>, 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, underscorin...

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Main Authors: Abdul Hannan Khan, Muhammad Bilal, Abid Mahmood, Nasir Rasool, Muhammad Usman Qamar, Muhammad Imran, Sebastian Ionut Toma, Oana Andreescu
Format: Article
Language:English
Published: MDPI AG 2024-09-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/17/9/1241
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Summary: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 IC<sub>50</sub> of 1.469 ± 0.02 µM. Further, in silico studies were performed to find the type of interactions between synthesized compounds and target proteins.
ISSN:1424-8247