CONICET-INFIQC, Departamento de Fisicoquímica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre s/n, Pabellón Argentina, Ciudad Universitaria, Córdoba X5000HUA, Argentina.
Federal University of Piaui, Laboratory of Research in Microbiology, Campus University Ministry Petrônio Portella, Ininga Neighborhood, Teresina, Piaui 64049-901, Brazil.
Bioorg Med Chem Lett. 2021 Jan 1;31:127670. doi: 10.1016/j.bmcl.2020.127670. Epub 2020 Nov 6.
Searching for new alternatives to antibiotic treatments is crucial to surmount the multidrug-resistant bacteria. In this work, the antimicrobial activity of synthetic imidazolidines was evaluated as well as their modulating effect on the resistance to fluoroquinolones in a S. aureus strain (SA-1199B), which overexpresses the norA gene that encodes the NorA efflux pump. Results showed weak antimicrobial activity (512 μg mL) for two fluorobenzylidene derivatives against this bacterial strain, while the other benzylidene derivatives were inactive. Despite this fact, both fluorinated compounds were able to enhance the activity of norfloxacin and ciprofloxacin against SA-1199B up to 6.4- and 3.2-fold, respectively. In addition, both derivatives potentiated the action of ethidium bromide against this strain, suggesting that the modulating effect probably involves the inhibition of the NorA efflux pump, which is in concordance with the fluorimetic assays and molecular docking analyses performed in this work.
寻找抗生素治疗的新替代品对于克服多药耐药菌至关重要。在这项工作中，评估了合成咪唑烷的抗菌活性及其对金黄色葡萄球菌（SA-1199B）菌株耐药性的调节作用，该菌株过度表达编码 NorA 外排泵的 norA 基因。结果表明，两种氟苄叉衍生物对该细菌菌株的抗菌活性较弱（512μg/mL），而其他苄叉衍生物则没有活性。尽管如此，这两种氟化化合物都能够将诺氟沙星和环丙沙星对 SA-1199B 的活性分别提高至 6.4 倍和 3.2 倍。此外，两种衍生物都增强了溴化乙锭对该菌株的作用，这表明调节作用可能涉及抑制 NorA 外排泵，这与本文进行的荧光测定和分子对接分析结果一致。
