The synthesis of 37 1‐(1H‐indol‐3‐yl)ethanamine derivatives, including 12 new compounds, was achieved through a series of simple and efficient chemical modifications. These indole derivatives displayed modest or no intrinsic anti‐staphylococcal activity. By contrast, several of the compounds restored, in a concentration‐dependent manner, the antibacterial activity of ciprofloxacin against Staphylococcus aureus strains that were resistant to fluoroquinolones due to overexpression of the NorA efflux pump. Structure–activity relationships studies revealed that the indolic aldonitrones halogenated at position 5 of the indole core were the most efficient inhibitors of the S. aureus NorA efflux pump. Among the compounds, (Z)‐N‐benzylidene‐2‐(tert‐butoxycarbonylamino)‐1‐(5‐iodo‐1H‐indol‐3‐yl)ethanamine oxide led to a fourfold decrease of the ciprofloxacin minimum inhibitory concentration against the SA‐1199B strain when used at a concentration of 0.5 mg L⁻¹. To the best of our knowledge, this activity is the highest reported to date for an indolic NorA inhibitor. In addition, a new antibacterial compound, tert‐butyl (2‐(3‐hydroxyureido)‐2‐(1H‐indol‐3‐yl)ethyl)carbamate, which is not toxic for human cells, was also found.

中文翻译：

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1-（1H-吲哚-3-基）乙胺衍生物作为强力金黄色葡萄球菌NorA外排泵抑制剂

通过一系列简单有效的化学修饰，合成了37种1–（1 H-吲哚-3-基）乙胺衍生物，包括12种新化合物。这些吲哚衍生物显示出中等或没有固有的抗葡萄球菌活性。相比之下，几种化合物以浓度依赖的方式恢复了环丙沙星对金黄色葡萄球菌菌株的抗菌活性，所述金黄色葡萄球菌菌株由于NorA外排泵的过表达而对氟喹诺酮类耐药。结构与活性之间的关系研究表明，在吲哚核心位置5处卤化的吲哚醛酮是金黄色葡萄球菌NorA外排泵的最有效抑制剂。在这些化合物中，（Z）‐ N苯亚甲基-2-（叔丁氧基羰基氨基）-1-（5-碘-1 H-吲哚-3-基）乙胺氧化物在下列条件下使用时对SA-1199B菌株的环丙沙星最低抑菌浓度降低了四倍。浓度为0.5 mg  L ^-1。据我们所知，这种活性是迄今为止吲哚类NorA抑制剂报道的最高活性。此外，还发现了一种新的抗菌化合物，叔丁基（2-（3-羟基脲基）-2-（1 H-吲哚-3-基）乙基）氨基甲酸酯，它对人体细胞无毒。