Antimalarial drugs have been suggested as promising scaffolds with anti-tubercular activities. In this work, we demonstrated, for the first time, the effectiveness of tafenoquine against mycobacteria. Firstly, tafenoquine inhibited the growth of Mycobacterium smegmatis and Mycobacterium tuberculosis with lower MICs values as compared to other antimalarial drugs, such as mefloquine, chloroquine, and primaquine. Importantly, tafenoquine was active against three multi-drug resistant strains of M. tuberculosis with MIC values similar to pan-sensitive strains, suggesting that tafenoquine is capable of evading the major mechanisms of resistance found in drug-resistant clinical isolates of M. tuberculosis. Importantly, tafenoquine displayed a synergistic effect when combined with mefloquine. In addition, tafenoquine displayed an improved activity compared to the groups treated with both isoniazid and rifampicin in the six-week nutrient starved M. tuberculosis cultures. This finding suggests that further investigations of tafenoquine against dormant mycobacteria are worth pursuing. Moreover, different concentrations of tafenoquine ranging from 1.25 to 80 μM displayed different effects against M. tuberculosis, from moderate (reduction of a 1.8 log CFU/mL) to potent bactericidal (reduction of a 4.2 log CFU/mL) activities. Tafenoquine may represent a hit for further drug optimization and for future clinical development as a new anti-mycobacterial agent, especially in cases of resistant and/or dormant forms of tuberculosis.

抗疟药物已被建议作为具有抗结核活性的有前途的支架。在这项工作中，我们首次证明了他非诺喹对分枝杆菌的有效性。首先，与甲氟喹、氯喹和伯氨喹等其他抗疟药相比，他非诺喹抑制耻垢分枝杆菌和结核分枝杆菌的生长，MIC 值较低。重要的是，他非诺喹对三种耐多药结核分枝杆菌菌株具有活性，其 MIC 值与泛敏感菌株相似，这表明他非诺喹能够规避在耐药结核分枝杆菌临床分离株中发现的主要耐药机制.重要的是，他非诺喹与甲氟喹合用时显示出协同作用。此外，在 6 周营养匮乏的结核分枝杆菌培养物中，与异烟肼和利福平治疗组相比，他非诺喹的活性有所提高。这一发现表明，进一步研究他非诺喹对休眠分枝杆菌的作用是值得追求的。此外，从 1.25 到 80 μM 的不同浓度的他非诺喹对M. tuberculosis表现出不同的效果，从中等（减少 1.8 log CFU/mL）到强效杀菌（减少 4.2 log CFU/mL）活性。Tafenoquine 可能代表进一步优化药物和作为一种新的抗分枝杆菌药物的未来临床开发，特别是在耐药和/或休眠形式的结核病的情况下。