University of Copenhagen, Faculty of Pharmaceutical Sciences, Department of Medicinal Chemistry, Denmark.
Bioorg Med Chem. 2012 Jul 15;20(14):4514-21. doi: 10.1016/j.bmc.2012.05.025. Epub 2012 May 18.
A library of 117 chalcones was screened for efflux pump inhibitory (EPI) activity against NorA mediated ethidium bromide efflux. Five of the chalcones (5-7, 9, and 10) were active and two chalcones (9 and 10) were equipotent to reserpine with IC(50)-values of 9.0 and 7.7 μM, respectively. Twenty chalcones were subsequently proved to be inhibitors of the NorA efflux pump in everted membrane vesicles. Compounds 5, 7, and 9 synergistically increased the effect of ciprofloxacin on Staphylococcus aureus. Our results suggest that chalcones might be developed into drugs for overcoming multidrug resistance based on efflux transporters of microorganisms.
研究人员合成了 117 种查耳酮库，筛选其对 NorA 介导的溴化乙锭外排的外排泵抑制 (EPI) 活性。其中 5 种查耳酮（5-7、9 和 10）具有活性，两种查耳酮（9 和 10）与利血平的活性相当，IC50-值分别为 9.0 和 7.7 μM。随后，有 20 种查耳酮被证明是外翻转膜囊泡中 NorA 外排泵的抑制剂。化合物 5、7 和 9 协同增加了环丙沙星对金黄色葡萄球菌的作用。我们的研究结果表明，查耳酮类化合物可能会被开发成基于微生物外排转运体的克服多药耐药性的药物。
