Development in the fields of natural-product-derived and synthetic small molecules is in stark contrast to the ongoing demand for novel antimicrobials to treat life-threatening infections caused by extended-spectrum β-lactamase producing Escherichia coli (ESBL E. coli). Therefore, there is an interest in the antibacterial activities of synthesized N-(4-methylpyridin-2-yl) thiophene-2-carboxamides (4a–h) against ESBL-producing E. coli ST131 strains. A blood sample was obtained from a suspected septicemia patient and processed in the Bactec Alert system. The isolate’s identification and antibacterial profile were determined using the VITEK 2® compact system. Multi-locus sequence typing of E. coli was conducted by identifying housekeeping genes, while ESBL phenotype detection was performed according to CLSI guidelines. Additionally, PCR was carried out to detect the blaCTX-M gene molecularly. Moreover, molecular docking studies of synthesized compounds (4a–h) demonstrated the binding pocket residues involved in the active site of the β-lactamase receptor of E. coli. The result confirmed the detection of E. coli ST131 from septicemia patients. The isolates were identified as ESBL producers carrying the blaCTX-M gene, which provided resistance against cephalosporins and beta-lactam inhibitors but sensitivity to carbapenems. Among the compounds tested, 4a and 4c exhibited high activity and demonstrated the best fit and interactions with the binding pocket of the β-lactamase enzyme. Interestingly, the maximum of the docking confirmations binds at a similar pocket region, further strengthening the importance of binding residues. Hence, the in vitro and molecular docking studies reflect the promising antibacterial effects of 4a and 4c compounds.

中文翻译：

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N-(4-methylpyridin-2-yl) Thiophene-2-Carboxamide 类似物对产超广谱-β-内酰胺酶的大肠杆菌 ST 131 临床菌株的抗菌功效

天然产物衍生和合成小分子领域的发展与对新型抗菌剂的持续需求形成鲜明对比，以治疗由产广谱 β-内酰胺酶的大肠杆菌 (ESBL E. coli) 引起的危及生命的感染。因此，人们对合成的 N-(4-甲基吡啶-2-基) 噻吩-2-甲酰胺 (4a–h) 对产 ESBL 大肠杆菌 ST131 菌株的抗菌活性感兴趣。从一名疑似败血症患者身上采集了一份血样，并在 Bactec Alert 系统中进行了处理。使用 VITEK 2® 紧凑型系统确定分离株的鉴定和抗菌谱。大肠杆菌的多位点序列分型是通过鉴定看家基因进行的，而ESBL表型检测是根据CLSI指南进行的。此外，进行 PCR 以分子检测 blaCTX-M 基因。此外，合成化合物 (4a–h) 的分子对接研究证明了大肠杆菌 β-内酰胺酶受体活性位点中涉及的结合口袋残基。结果证实从败血症患者中检测到大肠杆菌ST131。这些分离株被鉴定为携带 blaCTX-M 基因的 ESBL 生产者，该基因对头孢菌素和 β-内酰胺抑制剂具有抗性，但对碳青霉烯类药物敏感。在测试的化合物中，4a 和 4c 表现出高活性，并证明与 β-内酰胺酶的结合袋具有最佳配合和相互作用。有趣的是，最大的对接确认在相似的口袋区域结合，进一步加强了结合残基的重要性。因此，