Division of Medicinal Chemistry and Pharmacognosy. The Ohio State University, Columbus, OH, 43210, USA.
Microbial Infection and Immunity. The Ohio State University, Columbus, OH, 43210, USA.
Eur J Med Chem. 2020 Aug 1;199:112324. doi: 10.1016/j.ejmech.2020.112324. Epub 2020 Apr 28.
A series of Novel Bacterial Topoisomerase Inhibitors (NBTIs) employing a linker derived from isomannide were synthesized and evaluated. Reduced hERG inhibition was observed compared to structure-matched analogues with different linkers, and compound 6 showed minimal proarrhythmic potential using an in vitro panel of cardiac ion channels. Compound 6 also displayed excellent activity against fluoroquinolone-resistant MRSA (MIC = 2 μg/mL) and other Gram-positive pathogens.
我们合成并评估了一系列采用异甘露糖衍生 linker 的新型细菌拓扑异构酶抑制剂（NBTIs）。与具有不同 linker 的结构匹配类似物相比，观察到 hERG 抑制作用降低，并且化合物 6 在使用心脏离子通道的体外筛选模型中显示出最小的致心律失常潜力。化合物 6 对氟喹诺酮耐药性 MRSA（MIC = 2 μg/mL）和其他革兰氏阳性病原体也表现出优异的活性。
