A methoxylated flavone from Artemisia afra kills Mycobacterium tuberculosis.
A methoxylated flavone from Artemisia afra kills Mycobacterium tuberculosis.
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非洲蒿中的甲氧基黄酮可杀死结核分枝杆菌。
DOI：
10.1101/2023.10.11.561885
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Shell,ScarletS
中科院分区：
文献类型：
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作者：
Kellogg,JoshuaJ;Alonso,MariaNatalia;Jordan,RTeal;Xiao,Junpei;Cafiero,JuanHilario;Bush,Trevor;Towler,Melissa;Weathers,Pamela;Shell,ScarletS
由结核分枝杆菌（Mycobacterium tuberculosis，Mtb）引起的结核病是一种致命且使人衰弱的疾病，每年在全球影响数百万人。新出现的耐药Mtb菌株危及目前用于治疗结核病的联合疗法的功效;因此，迫切需要开发新的药物来对抗这种疾病。非洲蒿传统上用于南部非洲治疗疟疾，最近显示出抗结核病的活性。该属植物合成了大量的植物化学物质，其中许多已证明对人类健康的影响。转录组学分析表明，A. afra与A. annua或众所周知的抗疟疾青蒿素，表明存在于A.具有独特的行动模式的afra。采用生物化学计量学方法对A. AFRA导致甲氧基化黄酮（1）的分离，其对Mtb菌株MC 26230显示出相当大的活性。化合物1具有312.5 μg/mL的MIC，并且在处理6天后不产生活菌落。此外，1在杀死缺氧Mtb培养物方面是有效的，在处理2天后没有活的培养物。这表明A. afra是具有新作用机制的潜在强效抗结核病植物化学物质的来源。
Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current combination therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Artemisia afra is used traditionally in southern Africa to treat malaria and recently has shown anti tuberculosis activity. This genus synthesizes a prodigious number of phytochemicals, many of which have demonstrated human health effects. Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or the well-known antimalarial artemisinin, suggesting other phytochemicals present in A. afra with unique modes of action. A biochemometric study of A. afra resulted in the isolation of a methoxylated flavone (1), which displayed considerable activity against Mtb strain mc26230. Compound 1 had an MIC of 312.5 μg/mL and yielded no viable colonies after 6 days of treatment. In addition, 1 was effective in killing hypoxic Mtb cultures, with no viable cultures after 2 days of treatment. This suggested that A. afra is a source of potentially powerful anti-Mtb phytochemicals with novel mechanisms of action.