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

Abdul Hannan Khan ¹

Muhammad Bilal ¹

Abid Mahmood ²

Nasir Rasool ¹

Muhammad Usman Qamar ³

Muhammad Imran ⁴

Sebastian Ionut Toma ⁵

Oana Andreescu ⁵

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Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan |

Department of Pharmaceutical Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan |

Institute of Microbiology, Faculty of Life Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan |

⁴

Chemistry Department, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia |

⁵

Faculty of Medicine, Transilvania University of Brasov, 500036 Brasov, Romania |

Publication type: Journal Article

Publication date: 2024-09-20

MDPI

Journal: Pharmaceuticals

scimago Q1

SJR: 0.845

CiteScore: 6.1

Impact factor: 4.3

ISSN: 14248247

DOI: 10.3390/ph17091241

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PubMed ID: 39338403

Abstract

The emergence of extensively drug-resistant Salmonella Typhi (XDR-S. Typhi) 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 (3, 5a–5d) in good yields through the Suzuki reaction. Afterward, we evaluate their antibacterial activities against XDR-S. Typhi via the agar well diffusion method; 5d has the strongest antibacterial activity with MIC 6.25 (mg/mL). Moreover, in vitro Alkaline Phosphatase inhibitor activity was also determined; 5d 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.