天然产物研究与开发 ›› 2022, Vol. 34 ›› Issue (6): 1038-1046.doi: 10.16333/j.1001-6880.2022.6.017

• 开发研究 • 上一篇    下一篇

鬼箭羽、肉桂抗结核杆菌成分的逆向跟踪分离

张   越1,夏孟雨1,王   蕾1,赵   昕1,杨再昌1,2,3 *   

  1. 1贵州大学药学院,贵阳 550025;2贵州医科大学 省部共建药用植物功效与利用国家重点实验室,贵阳 550014;3南方科技大学 广东省普通高校植物细胞工厂分子设计重点实验室,深圳 518055
  • 出版日期:2022-06-28 发布日期:2022-06-30
  • 基金资助:
    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)

Determination of anti-Mycobacterium tuberculosis components of Caulis Euonymi Alati and Cinnamomi Cortex by reverse bioassay guided isolation

ZHANG yue1,XIA Meng-yu1,WANG Lei1,ZHAO Xin1,YANG Zai-chang1,2,3 *   

  1. 1School of Pharmaceutical Sciences,Guizhou University,Guiyang 550025,China;2State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medcial University,Guiyang 550014,China;3Key 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
  • Online:2022-06-28 Published:2022-06-30

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=1 μg/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。

关键词: 鬼箭羽, 肉桂, 结核杆菌, 逆向跟踪分离, 结构修饰

Abstract:

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=1 μg/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 of β-ketoacyl-ACP condensase III of Mbt.

Key words:

中图分类号:  R932