Identification of pyrvinium pamoate as an anti-tuberculosis agent in vitro and in vivo by SOSA approach amongst known drugs
Identification of pyrvinium pamoate as an anti-tuberculosis agent in vitro and in vivo by SOSA approach amongst known drugs
复制标题
通过 SOSA 方法在已知药物中鉴定双羟萘酸吡维铵作为体外和体内抗结核药
DOI：
10.1080/22221751.2020.1720527
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发表时间：
2020-01-01
影响因子：
13.2
通讯作者：
Zhang, Xiao-Lian
中科院分区：
文献类型：
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作者：
Guan, Qing;Zhan, Lingjun;Zhang, Xiao-Lian
摘要结核病（TB）是由结核分枝杆菌（M.tb）引起的，是世界范围内导致死亡的主要传染病。耐药M.结核病使控制结核病更加困难。选择性优化副作用（SOSA）方法使用旧药物作为新的药理学靶点。在本研究中，我们使用SOSA方法，成功地鉴定了双羟萘酸吡维铵（PP），它能够抑制分枝杆菌的生长，包括M。结核分枝杆菌H37 Rv、耻垢分枝杆菌、卡介苗、结核分枝杆菌M. tb H37 Ra和耐药M.从1280种已知药物库中体外分离结核病临床分离株。PP的MIC_（99）为对M. tb H37 Rv和耐药M.结核病临床分离株，范围为1.55 - 4.8 µg/mL。 PP可降低肺、脾、肝组织中的细菌集落形成单位（CFU），有效抑制M. tb H37 Rv、多药耐药M.结核分枝杆菌和广泛耐药（XDR）结核分枝杆菌感染的小鼠。我们的结果清楚地表明，PP具有潜在的应用于治疗结核病。
ABSTRACT 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.