A series of new azoalkyl ether imidazo[2,1-b]benzothiazoles were developed via a convenient synthetic procedure. The antimicrobial assays showed that a good number of the prepared derivatives exhibited significant inhibitory properties against most of the tested strains. Especially 2-methyl-5-nitroimidazole derivative 5a presented superior inhibit activity against MRSA and B. typhi with MIC = 4 μg/mL and MIC = 1 μg/mL, respectively. The highly active compound 5a showed low toxicity against mammalian cells without obvious triggering of the development of bacterial resistance, and it also possessed rapid bactericidal efficacy. Molecular docking study exposed that the active molecule 5a could interact with the active site of S. aureus gyrase through hydrogen bond. Quantum chemical studies were also performed to explain the high antibacterial activity. Further investigation revealed that compound 5a could significantly associate with gyrase–DNA complex by mean of hydrogen bonds and could efficiently intercalate into MRSA DNA to form 5a–DNA supramolecular complex, which impart potent bioactivity.

通过便利的合成方法开发了一系列新的偶氮烷基醚咪唑并[2,1- b ]苯并噻唑。抗菌测定表明，大量制备的衍生物对大多数测试菌株均表现出显着的抑制特性。特别是2-甲基-5-硝基咪唑衍生物5a对MRSA和伤寒杆菌表现出优异的抑制活性，分别为MIC = 4μg/ mL和MIC = 1μg/ mL。高活性化合物5a对哺乳动物细胞显示出低毒性，而没有明显触发细菌抗性的产生，并且还具有快速的杀菌功效。分子对接研究暴露出活性分子5a可以通过氢键与金黄色葡萄球菌回旋酶的活性位点相互作用。还进行了量子化学研究以解释高抗菌活性。进一步的研究表明，化合物5a可以通过氢键与回旋酶-DNA复合物显着缔合，并且可以有效地插入MRSA DNA中，形成5a- DNA超分子复合物，具有强大的生物活性。