A series of 2-aminothiophene derivatives (2AT) was synthesized and their bacterial growth and enzyme inhibitory effects against efflux proteins of Staphylococcus aureus leading to resistance to fluoroquinolones and erythromycin (ERY) were investigated. Compounds that most effectively decreases the minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) were assayed for their dose and time effects on the accumulation and efflux of ethidium bromide (EtBr) in the SA-1 strain. None of the compounds displayed antibacterial activity however, compounds 4, 9 and 13 enhanced the activity of CIP and ERY by 8- and 16-fold, respectively, and were able to restore the sensitivity of resistant strains, acting as typical efflux pump inhibitors (EPIs). Compounds 9, 11, 12 and 13 increased EtBr accumulation in a dose- and time-dependent manner, and compound 12 was also able to inhibit the EtBr efflux. Taken together, these results represent an important advance in the development of new EPIs, and demonstrate that 2AT represent a good scaffold for developing new antibiotic adjuvants.

中文翻译：

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新的2-氨基噻吩衍生物作为金黄色葡萄球菌外排泵抑制剂的合成和评价。

合成了一系列的2-氨基噻吩衍生物（2AT），研究了它们对金黄色葡萄球菌外排蛋白的细菌生长和酶抑制作用，导致其对氟喹诺酮类和红霉素（ERY）的抗性。分析了最有效降低环丙沙星（CIP）最低抑菌浓度（MIC）的化合物对SA-1菌株中溴化乙锭（EtBr）积累和流出的剂量和时间影响。这些化合物均未显示出抗菌活性，但是，化合物4、9和13分别将CIP和ERY的活性提高了8倍和16倍，并且能够恢复耐药菌株的敏感性，用作典型的外排泵抑制剂（ EPI）。化合物9、11、12和13以剂量和时间依赖性方式增加EtBr的积累，化合物12也能抑制EtBr外排。综上所述，这些结果代表了开发新的EPI的重要进展，并证明2AT代表了开发新的抗生素佐剂的良好支架。