Pipeline of anti-Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities.

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.