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InhA 抑制剂对非复制状态的结核分枝杆菌具有活性。

InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis.

机构信息

Infectious Disease Research Institute, Seattle, Washington, United States of America.

Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, United States of America.

出版信息

PLoS One. 2020 Nov 17;15(11):e0239354. doi: 10.1371/journal.pone.0239354. eCollection 2020.

DOI:10.1371/journal.pone.0239354
PMID:33201882
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7671525/
Abstract

We previously identified a diazaborine series with potential for development as a new tuberculosis drug. This series has activity in vitro and in vivo and targets cell wall biosynthesis via inhibition of InhA. The overall aim of this study was to determine whether InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis. We tested the ability of two molecules of the diazaborine series to kill non-replicating M. tuberculosis in the nutrient starvation model; both molecules were bactericidal, reducing viability by >3 logs in 21 days. Activity showed similar kill rates to other InhA inhibitors (isoniazid and NITD-916). We conclude that inhibition of InhA is bactericidal against nutrient-starved non-replicating M. tuberculosis.

摘要

我们之前发现了一系列具有开发成新型结核病药物潜力的二氮硼烷。该系列在体外和体内均具有活性，通过抑制 InhA 来靶向细胞壁生物合成。本研究的总体目标是确定 InhA 抑制剂是否对非复制的结核分枝杆菌具有活性。我们在营养饥饿模型中测试了二氮硼烷系列中的两种分子杀死非复制结核分枝杆菌的能力；这两种分子均具有杀菌作用，在 21 天内使存活率降低 3 个对数级以上。活性与其他 InhA 抑制剂（异烟肼和 NITD-916）相似。我们得出结论，抑制 InhA 对营养饥饿的非复制结核分枝杆菌具有杀菌作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/7671525/3b03b93c7162/pone.0239354.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/7671525/b70951befa8b/pone.0239354.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/7671525/5ef33b86e708/pone.0239354.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/7671525/3b03b93c7162/pone.0239354.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/7671525/b70951befa8b/pone.0239354.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/7671525/5ef33b86e708/pone.0239354.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/7671525/3b03b93c7162/pone.0239354.g003.jpg

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本文引用的文献

1
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2
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Antimicrob Agents Chemother. 2019 Mar 27;63(4). doi: 10.1128/AAC.02071-18. Print 2019 Apr.
3
Discovery of a cofactor-independent inhibitor of InhA.
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Front Cell Infect Microbiol. 2022 Sep 9;12:974101. doi: 10.3389/fcimb.2022.974101. eCollection 2022.
4
Overcoming through small molecule inhibitors to break down cell wall synthesis.通过小分子抑制剂克服以破坏细胞壁合成。
Acta Pharm Sin B. 2022 Aug;12(8):3201-3214. doi: 10.1016/j.apsb.2022.04.014. Epub 2022 Apr 27.
5
Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010-2020 Review.呈现处于不同药物研发阶段的新型抗结核药物的化学类别：2010 - 2020年综述
Pharmaceuticals (Basel). 2021 May 13;14(5):461. doi: 10.3390/ph14050461.
6
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7
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InhA的一种不依赖辅因子的抑制剂的发现。
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4
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Sci Transl Med. 2015 Jan 7;7(269):269ra3. doi: 10.1126/scitranslmed.3010597.
9
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