(-)-Epicatechin gallate serves as a novel new delhi metallo-β-lactamase-1(NDM-1)inhibitor  

一种新型NDM-1抑制剂:(–)-表儿茶素没食子酸酯

作　　者：Qian Wang Chennan Liu Jiangxue Han Sihan Liu Chunling Xiao Yan Guan Xinghua Li Ying Wang Xiao Wang Jianzhou Meng Maoluo Gan Yishuang Liu 王倩;刘琛楠;韩江雪;刘思含;肖春玲;关艳;李兴华;王颖;王潇;蒙建州;甘茂罗;刘忆霜(中国医学科学院北京协和医学院医药生物技术研究所,国家新药(微生物)筛选实验室,北京100050)

机构地区：[1]National Key Laboratory for Screening New Microbial Drugs,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2021年第9期716-724,共9页中国药学（英文版）

基　　金：Natural Sciences Foundation of China(NSFC,Grant No.81872913);National High-tech R&D Program(863 Program,Grant No.2015AA020911)。

摘　　要：Theβ-lactam antibiotic resistance caused by NDM-1 has become a major crisis of global public health.We have previously screened out(-)-epicatechin gallate(ECG)as a potent NDM-1 inhibitor.We further discussed its inhibitory effect and action mode in the present study.According to our results,ECG reversibly inactivated NDM-1 in a non-competitive mode,with an IC50 value of 4.48μM.ECG effectively recovered the activity of severalβ-lactam antibiotics against resistant strain harboring blaNDM-1.Especially,the effects on carbapenems were worth mentioning.The zinc supplement assay indicated a zinc-related mechanism of ECG.Different from traditional chelating agents,it showed low toxicity both in vivo and in vitro.In a word,our findings provided a promising NDM-1 inhibitor,ECG,which was able to assist carbapenems against NDM-1-producing strain.NDM-1导致的β-内酰胺类抗生素耐药问题已成为威胁全球公共卫生的重大危机。我们前期经筛选发现(–)-表儿茶素没食子酸酯是一种有效的NDM-1抑制剂,本文进一步探讨了其抑制活性和作用方式。结果显示,(–)-表儿茶素没食子酸酯以一种可逆的、非竞争性的模式抑制NDM-1的活性,IC_(50)值为4.48μM。(–)-表儿茶素没食子酸酯能有效恢复多种β-内酰胺类抗生素对NDM-1菌的抑菌活性,特别是对于碳青霉烯类抗生素有较显著的作用。锌离子回补实验结果提示,(–)-表儿茶素没食子酸酯发挥作用可能与对锌离子的影响有关,然而不同于传统螯合剂,它在体内外均展现出较低的毒性。综上所述,我们的结果显示(–)-表儿茶素没食子酸酯能够协助碳青霉烯类抗生素抑制NDM-1产生菌,是一种具有潜力的NDM-1抑制剂。

关 键 词：NDM-1 (-)-Epicatechin gallate INHIBITOR Antibiotics resistance 

分 类 号：R962[医药卫生—药理学]