Research Center of Biotechnology RAS, Moscow, Russia.
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Colorado, Fort Collins, USA.
Med Res Rev. 2021 Jul;41(4):2350-2387. doi: 10.1002/med.21798. Epub 2021 Mar 1.
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.
脓肿分枝杆菌复合体是一组新兴的病原体，难以治疗。目前尚无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应对这一全球威胁。可以通过两种平行策略来增强当前的抗脓肿分枝杆菌小分子药物开发过程-从新化学类别中发现化合物和商业药物再利用。本文综述了新型小分子药物发现的最新进展，特别是关注了来自五个不同化学类别的有前途的抑制剂的活性、作用机制和构效关系：苯并咪唑类、吲哚-2-甲酰胺类、苯并噻唑类、4-哌啶醇类和恶唑烷酮类。我们还讨论了其他一些处于药物开发早期阶段的有趣小分子，如噻嗪酮衍生物和苯并硼烷，总结了利福布汀、替加环素、贝达喹啉等可再利用药物的疗效的现有知识。最后，我们回顾了脓肿分枝杆菌中具有治疗意义的靶点，这些靶点可能值得未来进行药物和辅助治疗开发。
