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-(4-溴-3-甲基苯基)吡嗪-2-甲酰胺衍生物的简便合成、对临床分离的广泛耐药菌的抗菌活性、碱性磷酸酶抑制活性及对接研究

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

作者信息

Khan Abdul Hannan, Bilal Muhammad, Mahmood Abid, Rasool Nasir, Qamar Muhammad Usman, Imran Muhammad, Toma Sebastian Ionut, Andreescu Oana

机构信息

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

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

出版信息

Pharmaceuticals (Basel). 2024 Sep 20;17(9):1241. doi: 10.3390/ph17091241.

Abstract

The emergence of extensively drug-resistant Typhi (XDR-) 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 (-) in good yields through the Suzuki reaction. Afterward, we evaluate their antibacterial activities against XDR- via the agar well diffusion method; has the strongest antibacterial activity with MIC 6.25 (mg/mL). Moreover, in vitro Alkaline Phosphatase inhibitor activity was also determined; is the most potent compound, with an IC of 1.469 ± 0.02 µM. Further, in silico studies were performed to find the type of interactions between synthesized compounds and target proteins.

摘要

广泛耐药伤寒杆菌(XDR-)的出现对公共卫生构成了严重威胁,因为它对氟喹诺酮类和第三代头孢菌素具有耐药性。这种耐药性使治疗选择显著复杂化,凸显了对新治疗策略的迫切需求。在本研究中,我们通过铃木反应以良好的产率合成了吡嗪甲酰胺(-)。随后,我们通过琼脂孔扩散法评估了它们对XDR-的抗菌活性; 具有最强的抗菌活性,MIC为6.25(mg/mL)。此外,还测定了体外碱性磷酸酶抑制剂活性; 是最有效的化合物,IC为1.469±0.02µM。此外,还进行了计算机模拟研究,以确定合成化合物与靶蛋白之间的相互作用类型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21eb/11434897/a800ec0c99f0/pharmaceuticals-17-01241-g001.jpg

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