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.

中文翻译：

---

抗脓肿分枝杆菌小分子管道：可重复利用的药物和有前景的新型化学实体

脓肿分枝杆菌复合体是一组难以治疗的新兴病原体。没有有效的药物可成功治疗脓肿分枝杆菌肺部感染，英国或美国胸科学会推荐的现有药物方案与不良临床结果相关。因此，迫切需要新型抗菌药物来遏制这一全球威胁。目前的抗脓肿分枝杆菌小分子药物开发过程可以通过两种平行的策略来加强——从新化学类别中发现化合物和商业药物再利用。本综述重点介绍了发现新型小分子药物的最新进展，尤其侧重于来自五种不同化学类别的有前景的抑制剂（苯并咪唑、吲哚-2-甲酰胺、苯并噻唑）的活性、作用方式和构效关系、4-哌啶醇和恶唑烷酮。我们进一步讨论了一些其他有趣的小分子，例如处于药物开发早期阶段的噻唑酮衍生物和苯并硼氧杂环戊烷，并总结了当前关于可重复利用药物（例如利福布丁、泰地唑胺、贝达喹啉等）功效的知识。我们最后回顾了治疗感兴趣的目标可能值得未来药物和辅助治疗开发的脓肿分枝杆菌。