抗脓肿分枝杆菌活性的结核 F-ATP 合酶抑制剂 GaMF1。
Anti-Mycobacterium abscessus Activity of Tuberculosis F-ATP Synthase Inhibitor GaMF1.
机构信息
Nanyang Technological Universitygrid.59025.3b, School of Biological Sciences, Singapore, Republic of Singapore.
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.
出版信息
Antimicrob Agents Chemother. 2022 May 17;66(5):e0001822. doi: 10.1128/aac.00018-22. Epub 2022 Apr 28.
Abstract
New drug targets and molecules with bactericidal activity are needed against the respiratory mycobacterial pathogen Mycobacterium abscessus. Employing a lead repurposing strategy, the antituberculosis compound GaMF1 was tested against M. abscessus. Whole-cell and ATP synthesis assays demonstrated that GaMF1 inhibits growth and kills M. abscessus by targeting the F-ATP synthase. GaMF1's anti-M. abscessus activity increased in combination with clofazimine, rifabutin, or amikacin. The study expands the repertoire of anti-M. abscessus compounds targeting oxidative phosphorylation.
摘要
需要针对呼吸道分枝杆菌病原体脓肿分枝杆菌寻找新的药物靶点和具有杀菌活性的分子。本研究采用重新定位先导化合物策略，检测了抗结核化合物 GaMF1 对脓肿分枝杆菌的作用。全细胞和 ATP 合成测定表明，GaMF1 通过靶向 F-ATP 合酶抑制生长并杀死脓肿分枝杆菌。GaMF1 与氯法齐明、利福布汀或阿米卡星联合使用可增强其抗脓肿分枝杆菌活性。该研究扩展了针对氧化磷酸化的抗脓肿分枝杆菌化合物库。
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3
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