摘要
本研究采用逆向跟踪分离,证实松萝酸、肉桂醛分别是鬼箭羽和肉桂的最强抗结核杆菌成分。对松萝酸、肉桂醛进行结构修饰,得到7个衍生物(化合物1~7),具有较强的抗结核杆菌活性,其中2-(2-benzofuranylmethylene)hydrazinecarbothioamide(1)活性最强(MIC_(50)=1μg/mL)。通过分子对接、定量PCR、显微成像、杀菌试验,推测化合物1的作用机制与结核杆菌干预β-酮脂酰-ACP合成酶Ⅲ有关。
In this study,reverse bioassay guided isolation was used to discover the anti-Mycobacterium tuberculosis(Mbt)components of Caulis Euonymi Alati and Cinnamomi Cortex.The results indicated that usnic acid and cinnamaldehyde were the strongest anti-Mycobacterium tuberculosis components of Caulis Euonymi Alati and Cinnamomi Cortex,respectively.The structure of usnic acid and cinnamaldehyde was modified to obtain 7 derivatives(compounds 1-7),which have strong anti-Mtb activity.Among them,2-(2-benzofuranylmethylene)hydrazinecarbothioamide(1)showed the strongest activity against Mbt(MIC_(50)=1μg/mL).Through molecular docking,quantitative PCR,microscopic imaging,and bactericidal tests,it is speculated that the mechanism of action of compound 1 anti-Mtb is related to the intervention ofβ-ketoacyl-ACP condensaseⅢof Mbt.
作者
张越
夏孟雨
王蕾
赵昕
杨再昌
ZHANG yue;XIA Meng-yu;WANG Lei;ZHAO Xin;YANG Zai-chang(School of Pharmaceutical Sciences,Guizhou University,Guiyang 550025,China;State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medcial University,Guiyang 550014,China;Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes,Institute of Plant and Food Science,Department of Biology,Southern University of Science and Technology,Shenzhen 518055,China)
出处
《天然产物研究与开发》
CAS
CSCD
2022年第6期1038-1046,共9页
Natural Product Research and Development
基金
国家自然科学基金(82060635,81760629)
贵州省社会发展科技攻关项目(SY字[2013]3058号)
“国家重点实验室开放课题”及“黔科合平台人才”([2017]5101)
广东省普通高校植物细胞工厂分子设计重点实验室开放项目(KLMDPCF202102)。
关键词
鬼箭羽
肉桂
结核杆菌
逆向跟踪分离
结构修饰
Caulis Euonymi Alati
Cinnamomi Cortex
Mycobacterium tuberculosis
reverse bioassay guided isolation
structural modification
