靶向FtsZ先导化合物的筛选及其抗结核作用探讨

Screening of Fts Z-targeted compounds and their anti-tuberculosis activities

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。

Objective： To discover novel anti-tuberculosis compounds that target mycobacterium tuberculosis Fts Z. Methods： The study focused on mycobacterium tuberculosis Fts Z,and the virtual screening of Discovery Studio was used to screen the compounds. Then,the selected compounds were tested to determine their IC50 of the GTPase activity of Fts Z. The anti-tuberculosis activity was evaluated on Mycobacterium smegmatis. Results： Three compounds with higher scores from compound library（ 5 000 compounds） were obtained. These compounds could inhibit GTPase activity of Fts Z with IC50 values of 9. 96,14. 02 and 16. 17 μmol·L^-1,respectively. Additionally,all these compounds had anti-tuberculosis activities. Conclusion： The three novel compounds will contribute to the anti-tuberculosis drug discovery,and provide new information for structure-based virtual screening.