Establishment and application of the screening model of the Mycobacterium tuberculosis β-lactamase BlaC inhibitors

作     者：刘忆霜 郑佳音 黄树超 关艳 肖春玲 Yishuang Liu;Jiayin Zheng;Shuchao Huang;Yan Guan;Chunling Xiao

作者机构：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 首都医科大学神经生物学系北京100069 

出 版 物：《Journal of Chinese Pharmaceutical Sciences》 (中国药学（英文版）)

年 卷 期：2016年第25卷第3期

页      面：189-195页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：Fundamental Research Funds for Central Public Welfare Research Institutes(Grant No.2015PT350001) National Major Scientific and Technological Special Project for “Significant New Drugs Development”(Grant No.2015ZX09102007-009) 

主　　题：Mycobacterium tuberculosis β-Lactamase BlaC High-through screening model Anti-tuberculosis drug synergistic agents 

摘      要：With the continuous emergence and rapid spread of multidrug-resistant and extensively-drug-resistant Mycobacterium tuberculosis strains, it is imperative to develop novel therapies against this bacterium. The intrinsic β-lactam resistance of M. tuberculosis is primarily due to the production of an Ambler class-A β-lactamase BlaC, which limits the application of β-lactam antibiotics in the treatment of tuberculosis. Therefore, the inhibitors of BlaC could be novel anti-tuberculosis drug synergistic agents to recover the sensibility of M. Tuberculosis to the β-lactam antibiotics. In the present study, BlaC of M. tuberculosis was expressed and purified to establish a screening model of the BlaC inhibitors. The screening conditions were determined, and the screening model was evaluated to fit for the high throughput screening. A total of 22 BlaC inhibitors were screened out from 26 400 compound samples with a positive rate of 0.083%. Taken together, our findings lay the foundation for the discovery of novel anti-tuberculosis drug synergistic agents in clinic.