Background: Drug-resistant infections kill hundreds of thousands of people globally every year. In previous work, we found that tri-methoxy- and pyridine-substituted imidazoles show strong antibacterial activities. Objective: The aim of this work was to investigate the antibacterial activities and bacterial resistances of imidazoles bearing an aromatic heterocyclic, alkoxy, or polycyclic moiety on the central ring. Methods: Three series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4- yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles (13a-e, 14a-d, and 15a-f) were synthesized and their antibacterial activity was evaluated. The structures were confirmed by their 1H NMR, 13C NMR, and HRMS spectra. All the synthesized compounds were screened against Gram-positive, Gramnegative, and multidrug-resistant bacterial strains. Results: More than half of the compounds showed moderate or strong antibacterial activity. Among them, compound 13e (MICs = 1-4 μg/mL) showed the strongest activity against Gram-positive and drug-resistant bacteria as well as high selectivity against Gram-negative bacteria. Furthermore, it showed no cytotoxicity against HepG2 cells, even at 100 μM, and no hemolysis at 20 μM. Conclusion: These results indicate that compound 13e is excellent candicate for further study as a potential antibacterial agent.

中文翻译：

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含咪唑并[2,1-b][1,3,4]噻二唑基团的咪唑衍生物的合成及抗菌性能评价


背景：耐药性感染每年导致全球数十万人死亡。在之前的工作中，我们发现三甲氧基和吡啶取代的咪唑表现出很强的抗菌活性。目的：本工作的目的是研究中心环上带有芳香杂环、烷氧基或多环部分的咪唑的抗菌活性和细菌耐药性。方法：三个系列的2-环丙基-5-(5-(6-甲基吡啶-2-基)-2-取代-1H-咪唑-4-基)-6-苯基咪唑[2,1-b][1,合成了 3,4]噻二唑（13a-e、14a-d 和 15a-f）并评估了它们的抗菌活性。结构通过 1H NMR、13C NMR 和 HRMS 谱得到证实。所有合成的化合物均针对革兰氏阳性、革兰氏阴性和多重耐药菌株进行筛选。结果：超过一半的化合物表现出中等或较强的抗菌活性。其中，化合物13e（MIC = 1-4 μg/mL）对革兰氏阳性菌和耐药菌表现出最强的活性，并对革兰氏阴性菌具有高选择性。此外，即使在 100 μM 浓度下，它也没有表现出对 HepG2 细胞的细胞毒性，并且在 20 μM 浓度下也没有溶血。结论：这些结果表明化合物 13e 是作为潜在抗菌剂进行进一步研究的极好候选者。