Korkegian Aaron, O'Malley Theresa, Xia Yi, Zhou Yasheen, Carter David S, Sunde Bjorn, Flint Lindsay, Thompson Dean, Ioerger Thomas R, Sacchettini Jim, Alley M R K, Parish Tanya
TB Discovery Research, Infectious Disease Research Institute, Seattle, WA, USA.
Anacor Pharmaceuticals, Palo Alto, CA, USA.
Tuberculosis (Edinb). 2018 Jan;108:96-98. doi: 10.1016/j.tube.2017.11.003. Epub 2017 Nov 7.
We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC) as low as 5.1 μM and no cytotoxicity against eukaryotic cells (IC > 50 μM). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. Mutations suggest that Ndh may be the target of this series.
我们鉴定出了一系列对结核分枝杆菌具有活性的新型7-苯基苯并硼唑化合物。这些化合物具有一定范围的活性，抑制浓度（IC）低至5.1 μM，且对真核细胞无细胞毒性（IC > 50 μM）。这些化合物对在THP-1巨噬细胞中培养的细胞内分枝杆菌具有活性。我们分离并鉴定了在NADH脱氢酶（Ndh）或调节蛋白Mce3R中发生突变的耐药突变体。这些突变表明Ndh可能是该系列化合物的作用靶点。
