The ability to respire and generate adenosine triphosphate (ATP) is essential for the physiology, persistence, and pathogenicity of Mycobacterium tuberculosis, which causes tuberculosis. By employing a lead repurposing strategy, the malarial cytochrome bc1 inhibitor SCR0911 was tested against mycobacteria. Docking studies were carried out to reveal potential binding and to understand the binding interactions with the target, cytochrome bcc. Whole-cell-based and in vitro assays demonstrated the potency of SCR0911 by inhibiting cell growth and ATP synthesis in both the fast- and slow-growing M. smegmatis and M. bovis bacillus Calmette-Guérin, respectively. The variety of biochemical assays and the use of a cytochrome bcc deficient mutant strain validated the cytochrome bcc oxidase as the direct target of the drug. The data demonstrate the broad-spectrum activity of SCR0911 and open the door for structure-activity relationship studies to improve the potency of new mycobacteria specific SCR0911 analogues.

中文翻译：

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抗疟疾细胞色素bcc氧化酶抑制剂SCR0911的抗结核活性。

呼吸和产生三磷酸腺苷（ATP）的能力对于引起结核病的结核分枝杆菌的生理，持久性和致病性至关重要。通过采用铅再利用策略，对疟疾细胞色素bc1抑制剂SCR0911进行了分枝杆菌测试。进行了对接研究，以揭示潜在的结合并了解与靶标细胞色素bcc的结合相互作用。基于全细胞的体外试验证明了通过抑制快速增长和缓慢增长的耻垢分枝杆菌和牛分枝杆菌卡梅特-盖林中的细胞生长和ATP合成，SCR0911的功效。各种生化分析方法和细胞色素bcc缺陷型突变株的使用证实了细胞色素bcc氧化酶是药物的直接靶标。