Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus.
Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus.
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DOI：
10.1128/aac.00669-22
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发表时间：
2022-09-20
影响因子：
4.9
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中科院分区：
文献类型：
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三环吡咯并嘧啶类化合物（TPPs）是一类抑制DNA促旋酶ATP酶活性的新型抗菌药物。TPP8是这一类的代表，在体外对结核分枝杆菌有活性。自发性TPP8抗性突变定位于M.该化合物对重组M.酵素。TPP8在巨噬细胞和小鼠感染研究中的进一步分析证明了对M.离体和体内培养。
Tricyclic pyrrolopyrimidines (TPPs) are a new class of antibacterials inhibiting the ATPase of DNA gyrase. TPP8, a representative of this class, is active against Mycobacterium abscessus in vitro. Spontaneous TPP8 resistance mutations mapped to the ATPase domain of M. abscessus DNA gyrase, and the compound inhibited DNA supercoiling activity of recombinant M. abscessus enzyme. Further profiling of TPP8 in macrophage and mouse infection studies demonstrated proof-of-concept activity against M. abscessus ex vivo and in vivo.