靶向FtsZ先导化合物的筛选及其抗结核作用探讨

发布时间：2018-03-19 05:05

本文选题：结核分枝杆菌　切入点：Fts　出处：《中国新药杂志》2015年05期 　论文类型：期刊论文

【摘要】：目的:筛选可能作用于结核分枝杆菌Fts Z靶点的化合物,并且评价化合物的抗结核作用。方法:以结核分枝杆菌Fts Z为靶点,通过Discovery Studio虚拟筛选,选择候选化合物。测定候选化合物抑制Fts Z的GTP酶活性的IC50,并通过对耻垢分枝杆菌抑制的MIC评价其抗结核作用。结果:对化合物库(5 000个化合物)虚拟筛选,得到3个打分较高的化合物。体外实验发现这3个化合物能够在体外抑制结核分枝杆菌Fts Z的GTP酶活性,其IC50分别为9.96,14.02,16.17μmol·L-1。并且这3个化合物都具有抗耻垢分枝杆菌活性。结论:通过虚拟筛选得到的3个化合物将为抗结核药物的研发提供线索,也对药物虚拟筛选和基于结构的药物开发提供新的信息。
[Abstract]:Objective: to screen the compounds that might act on the target of Fts Z of Mycobacterium tuberculosis, and to evaluate the antituberculous effect of the compounds. Methods: using Fts Z of Mycobacterium tuberculosis as the target, Discovery Studio was used to screen the compounds. The activity of GTP enzyme of Fts Z was determined by IC50, and its antituberculous effect was evaluated by MIC inhibited by Mycobacterium smearicus. Results: a virtual screening of 5 000 compounds in compound library was carried out. Three compounds with high score were obtained. The results showed that the three compounds could inhibit the GTP enzyme activity of Mycobacterium tuberculosis Fts Z in vitro. The IC50 of these three compounds were 9.96 渭 mol 路L ~ (-1) and 14.02 渭 mol 路L ~ (-1), respectively. Conclusion: the three compounds obtained by virtual screening will provide clues for the research and development of antituberculous drugs. It also provides new information for virtual drug screening and structure-based drug development.
【作者单位】：中国医学科学院医药生物技术研究所国家新药(微生物)筛选实验室;药物研究所医药生物技术研究所国家新药(微生物)筛选实验室;
【基金】：国家自然科学基金(81302816,81321004)
【分类号】：R96

【相似文献】