As the development of novel antibiotics has been at a halt for several decades, chemically enhancing existing drugs is a very promising approach to drug development. Herein, we report the preparation of twelve organic salts and ionic liquids (OSILs) from ciprofloxacin and norfloxacin as anions with enhanced antimicrobial activity. Each one of the fluoroquinolones (FQs) was combined with six different organic hydroxide cations in 93–100% yield through a buffer-assisted neutralization methodology. Six of those were isomorphous salts while the remaining six were ionic liquids, with four of them being room temperature ionic liquids. The prepared compounds were not toxic to healthy cell lines and displayed between 47- and 1416-fold more solubility in water at 25 and 37 °C than the original drugs, with the exception of the ones containing the cetylpyridinium cation. In general, the antimicrobial activity against Klebsiella pneumoniae was particularly enhanced for the ciprofloxacin-based OSILs, with up to ca. 20-fold decreases of the inhibitory concentrations in relation to the parent drug, while activity against Staphylococcus aureus and the commensal Bacillus subtilis strain was often reduced. Depending on the cation–drug combination, broad-spectrum or strain-specific antibiotic salts were achieved, potentially leading to the future development of highly bioavailable and safe antimicrobial ionic formulations.

中文翻译：

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来自氟喹诺酮类的高生物利用度有机盐和离子液体的抗菌活性。

由于新型抗生素的开发已经停止了数十年，因此化学增强现有药物是药物开发中非常有前途的方法。在此，我们报道了由环丙沙星和诺氟沙星作为具有增强抗菌活性的阴离子制备十二种有机盐和离子液体（OSIL）。通过缓冲液辅助中和方法，将每种氟喹诺酮（FQs）与六种不同的有机氢氧化物阳离子混合，产率为93-100％。其中六种为同晶盐，其余六种为离子液体，其中四种为室温离子液体。制备的化合物对健康细胞系无毒，在25和37°C的水中显示的溶解度比原始药物高47到1416倍，除了那些含有十六烷基吡啶鎓阳离子的。一般而言，对对于基于环丙沙星的OSIL，肺炎克雷伯菌尤其有效，最高可达。与母体药物相比，抑制浓度降低了20倍，而对金黄色葡萄球菌和共生枯草芽孢杆菌菌株的活性通常降低了。根据阳离子-药物组合的不同，获得了广谱或菌株特异性的抗生素盐，这可能导致未来开发出具有高生物利用度和安全性的抗菌离子制剂。