Objective: To discover novel inhibitors specially targeting Mycobacteria tuberculosis ( MTB) pantothenate synthetase (PS) , and provide a foundation for the development of novel antitubercular drugs. Methods; The PS of MTB H37Rv was cloned, expressed, and purified. The screening system was build based on the assay of enzyme activity. The potential inhibitors were screened. The enzyme kinetics of lead hit was studied. The antitubercular activity was evaluated by the micro-assay of MTB with celerity and sensitivity. Results; The recombi-nant PS had nature activity. The system of enzyme activity was build and optimized. A novel PS inhibitor was found by the screening. The inhibitor had a dramatically antitubercular activity. Conclusion: A novel inhibitor of MTB PS with antitubercular activity has been found.%目的:获得特异性靶向结核分枝杆菌泛酸合成酶的抑制剂,为开发针对该靶点的新型抗结核药物奠定基础.方法:重组表达结核分支杆菌H37Rv的泛酸合成酶,以酶活测定体系为基础构建高通量筛选模型,对筛选到的酶抑制剂进行酶促动力学研究,并运用分枝杆菌微量直观快速药敏试验法测定其体外抗结核活性.结果:得到了具有天然活性的泛酸合成酶,建立并优化了酶活测定体系及筛选模型,应用模型筛选得到了具有新结构的抑制剂.评价结果显示,该抑制剂具有显著的体外抗结核活性.结论:获得了具有显著体外抗结核活性的新型泛酸合成酶抑制剂.
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