Pipeline of anti-Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities.
Pipeline of anti-Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities.
复制标题
DOI：
10.1002/med.21798
复制
发表时间：
2021-07
影响因子：
13.3
通讯作者：
Makarov V
中科院分区：
文献类型：
--
作者：
Egorova A;Jackson M;Gavrilyuk V;Makarov V
结核分枝杆菌复合体是一组新出现的病原体，治疗困难，目前尚无有效的药物治疗成功的结核分枝杆菌。肺部感染治疗和英国或美国胸科学会推荐的现有药物方案与不良临床结局相关。因此，迫切需要新型抗菌药物来遏制这一全球威胁。目前，M。小分子药物的开发过程可以通过两种并行的策略来增强-从新的化学类别中发现化合物和商业药物再利用。本文综述了近年来新型小分子药物的研究进展，重点介绍了苯并咪唑类、吲哚-2-甲酰胺类、苯并噻唑类、4-哌啶酮类和恶唑烷酮类等5类抑制剂的活性、作用方式和构效关系。我们进一步讨论了其他一些有趣的小分子，如thiacetazone衍生物和benzoboroxoles，这是在药物开发的早期阶段，并总结了目前的知识，可重复利用的药物，如利福伯胺，tedizolid，贝达喹啉，和其他的疗效。最后，我们回顾了M的治疗兴趣的目标。这可能是值得未来的药物和辅助治疗的发展。
The Mycobacterium abscessus complex is a group of emerging pathogens that are difficult to treat. There are no effective drugs for successful M. abscessus pulmonary infection therapy, and existing drug regimens recommended by the British or the American Thoracic Societies are associated with poor clinical outcomes. Therefore, novel antibacterial drugs are urgently needed to contain this global threat. The current anti-M. abscessus small-molecule drug development process can be enhanced by two parallel strategies—discovery of compounds from new chemical classes and commercial drug repurposing. This review focuses on recent advances in the finding of novel small-molecule agents, and more particularly focuses on the activity, mode of action and structure–activity relationship of promising inhibitors from five different chemical classes—benzimidazoles, indole-2-carboxamides, benzothiazoles, 4-piperidinoles, and oxazolidionones. We further discuss some other interesting small molecules, such as thiacetazone derivatives and benzoboroxoles, that are in the early stages of drug development, and summarize current knowledge about the efficacy of repurposable drugs, such as rifabutin, tedizolid, bedaquiline, and others. We finally review targets of therapeutic interest in M. abscessus that may be worthy of future drug and adjunct therapeutic development.
登录
查看更多内容
影响因子：
6.7
作者：
Baranyai, Zsuzsa;Kratky, Martin;Bosze, Szilvia
通讯作者：
Bosze, Szilvia
影响因子：
4.9
作者：
Bermudez, LE;Kolonoski, P;Young, LS
通讯作者：
Young, LS
影响因子：
6.4
作者：
Bald D;Villellas C;Lu P;Koul A
通讯作者：
Koul A
影响因子：
4.9
作者：
Abdalla, Maher Y.;Switzer, Barbara L.;Britigan, Bradley E.
通讯作者：
Britigan, Bradley E.
影响因子：
9.4
作者：
Alexander, David C.;Vasireddy, Ravikiran;Wallace, Richard J., Jr.
通讯作者：
Wallace, Richard J., Jr.