Li Linsen, Okumu Antony, Dellos-Nolan Sheri, Li Zoe, Karmahapatra Soumendrakrishna, English Anthony, Yalowich Jack C, Wozniak Daniel J, Mitton-Fry Mark J
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.
Bioorg Med Chem Lett. 2018 Aug 1;28(14):2477-2480. doi: 10.1016/j.bmcl.2018.06.003. Epub 2018 Jun 1.
Novel bacterial type II topoisomerase inhibitors (NBTIs) constitute a promising new class of antibacterial agents. We report a series of NBTIs with potent anti-staphylococcal activity and diminished hERG inhibition. Dioxane-linked compound 9 demonstrated MICs ≤1 μg/mL against both methicillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA), accompanied by reduced hERG inhibition as compared to cyclohexane- or piperidine-linked analogs.
新型细菌II型拓扑异构酶抑制剂（NBTIs）构成了一类有前景的新型抗菌剂。我们报道了一系列具有强效抗葡萄球菌活性且对人醚 - 去极化相关基因（hERG）抑制作用减弱的NBTIs。与环己烷或哌啶连接的类似物相比，二恶烷连接的化合物9对甲氧西林敏感金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA）的最低抑菌浓度（MIC）均≤1μg/mL，同时hERG抑制作用降低。
