Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) bacteria, is a leading infectious cause of mortality worldwide. The emergence of drug-resistant M. tb has made control of TB more difficult. The selective optimization of side activities (SOSA) approach uses old drugs for new pharmacological targets. In the present study by using SOSA approach, we have successfully identified pyrvinium pamoate (PP) which is capable of inhibiting the growth of mycobacteria, including M. tb H37Rv, Mycobacterium smegmatis, Bacille Calmette-Guérin (BCG), M. tb H37Ra, and drug-resistant M. tb clinical isolates in vitro from 1280 known drugs library. The MIC99 of PP, the minimum inhibitory concentration that inhibits more than 99% of M. tb H37Rv and the drug-resistant M. tb clinical isolates, ranges from 1.55 to 4.8 µg/mL. Importantly, PP could reduce the bacterial colony-forming units (CFUs) in lung, spleen and liver tissues, and effectively inhibit inflammatory response in M. tb H37Rv, multidrug-resistant (MDR) M. tb and extensively drug-resistant (XDR) M.tb-infected mice. Our results clearly show that the PP has the potential application for treatment of TB.

中文翻译：

---

通过 SOSA 方法在已知药物中鉴定吡维铵作为体外和体内抗结核剂。

结核病 (TB) 由结核分枝杆菌 (M.tb) 细菌引起，是全球范围内导致死亡的主要原因。耐药结核分枝杆菌的出现使结核病的控制更加困难。副活性选择性优化 (SOSA) 方法使用旧药物作为新药理学靶点。在本研究中，通过使用 SOSA 方法，我们成功地鉴定了能够抑制分枝杆菌生长的双羟萘酸吡维铵 (PP)，包括 M. tb H37Rv、Mycobacterium smegmatis、Bacille Calmette-Guérin (BCG)、M. tb H37Ra、从 1280 种已知药物库中体外分离出耐药结核分枝杆菌。PP 的 MIC99，即抑制超过 99% 的结核分枝杆菌 H37Rv 和耐药结核分枝杆菌临床分离株的最低抑制浓度，范围为 1.55 至 4.8 µg/mL。重要的，PP可以减少肺、脾和肝组织中的细菌菌落形成单位（CFUs），有效抑制结核分枝杆菌H37Rv、多重耐药（MDR）结核分枝杆菌和广泛耐药（XDR）结核分枝杆菌的炎症反应。结核病感染的小鼠。我们的结果清楚地表明，PP 具有治疗结核病的潜在应用。