Department of Pharmaceutical Sciences, University of Perugia, via del Liceo 1, 06123, Perugia, Italy.
John D. Dingell Department of Veterans Affairs Medical Centre, Division of Infectious Diseases, School of Medicine, Wayne State University, Detroit, MI 48201, United States.
Eur J Med Chem. 2018 Jul 15;155:428-433. doi: 10.1016/j.ejmech.2018.06.013. Epub 2018 Jun 6.
The alarming and rapid spread of antimicrobial resistance among bacteria represents a high risk for global health. Targeting factors involved in resistance to restore the activity of failing antibiotics is a promising strategy to overcome this urgent medical need. Efflux pump inhibitors are able to increase antibiotic concentrations in bacteria, thus they can be considered true antimicrobial resistance breakers. In this work, continuing our studies on inhibitors of the Staphylococcus aureus NorA pump, we designed, synthesized and biologically evaluated novel 2-phenylquinoline derivatives starting from our hits 1 and 2. Two of the synthesized compounds (6 and 7) bearing a C-6 benzyloxy group showed the best NorA inhibition activity, thereby providing an excellent starting point to direct future chemical optimizations.
细菌对抗生素耐药性的惊人且迅速传播对全球健康构成了高风险。针对耐药性相关因素以恢复失效抗生素的活性是克服这一紧迫医疗需求的有前途的策略。外排泵抑制剂能够增加细菌中的抗生素浓度，因此它们可以被认为是真正的抗微生物耐药性破坏剂。在这项工作中，我们继续研究金黄色葡萄球菌 NorA 泵的抑制剂，从我们的先导化合物 1 和 2 出发，设计、合成并对新型 2-苯基喹啉衍生物进行了生物评价。两个含有 C-6 苄氧基的合成化合物（6 和 7）表现出最好的 NorA 抑制活性，从而为进一步的化学优化提供了一个极好的起点。
