Efficient procedures are herein reported for the synthesis of novel hybrid thiazoles via a one‐pot three‐component protocol. The protocol involves the reaction of novel aldehyde, thiosemicarbazide and halogen‐containing reagents in solvent‐ and catalyst‐free conditions. The structures of the new thiazoles were elucidated by elemental analyses and spectroscopic data. The in‐vitro antibacterial screening and MurB enzyme inhibition assays were performed for the novel thiazoles. The thiazol‐4(5H)‐one derivative 6d, with p‐MeO, exhibits the best antibacterial activities with minimum inhibitory concentration values of 3.9, 3.9, 7.8, and 15.6 μg/ml against Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus mutans, and Escherichia coli, respectively, as compared to the reference antibiotic drugs. It also exhibits the highest inhibition of the MurB enzyme with an IC50 of 8.1 μM. The structure–activity relationship was studied to determine the effect of the structures of the newly prepared molecules on the strength of the antibacterial activities. Molecular docking was also performed to predict the binding modes of the new thiazoles in the active sites of the E. coli MurB enzyme.

中文翻译：

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作为有效抗菌剂和 MurB 抑制剂的新型噻唑的合成、体外和计算机研究

本文报道了通过一锅三组分方案合成新型杂化噻唑的有效程序。该方案涉及新型醛、氨基硫脲和含卤素试剂在无溶剂和无催化剂条件下的反应。通过元素分析和光谱数据阐明了新噻唑的结构。对新型噻唑类药物进行了体外抗菌筛选和 MurB 酶抑制试验。含有 p-MeO 的噻唑-4(5H)-one 衍生物 6d 表现出最好的抗菌活性，对金黄色葡萄球菌、肺炎克雷伯菌、变形链球菌和变形链球菌的最小抑菌浓度分别为 3.9、3.9、7.8 和 15.6 μg/ml。大肠杆菌分别与参考抗生素药物相比。它还表现出对 MurB 酶的最高抑制，IC50 为 8.1 μM。研究了构效关系以确定新制备的分子的结构对抗菌活性强度的影响。还进行了分子对接以预测新噻唑在大肠杆菌 MurB 酶活性位点的结合模式。