结核分枝杆菌FtsZ抑制剂的筛选和活性研究

Screening and activity of Mycobacterium tuberculosis FtsZ inhibitors

目的筛选结核分枝杆菌FtsZ的特异性抑制剂,为抗结核药物的研发提供先导化合物。方法应用本实验室已经建立的结核分枝杆菌FtsZ抑制剂筛选模型对化合物库进行筛选,获得能够抑制FtsZ的化合物202E,对其进行IC50以及分子水平活性测定,并利用DS 4.0软件将化合物202E与FtsZ的活性位点进行对接。结果化合物202E能够抑制结核分枝杆菌FtsZ的GTP酶活性,其IC50为15.46μmol/L。202E还能够抑制FtsZ蛋白的聚合。通过分子对接,发现202E能够与FtsZ的GTP结合位点结合,抑制FtsZ的GTP酶活性。结论化合物202E是活性较好的结核分枝杆菌FtsZ抑制剂。

Objective The aim of the study is to find new anti-tuberculosis agents which can inhibit the activity of Fts Z in Mycobacterium tuberculosis Methods By using the high-throughput screening model for inhibitors of Mycobacterium tuberculosis Fts Z, compound 202 E was selected. We assessed the IC50 value and molecular level activity of 202 E. And then we docked compound 202 E with active site of Fts Z. Results Compound 202 E was found to inhibit GTPase activity of Mycobacterium tuberculosis Fts Z with IC50 of 15.46 μmol/L. 202 E also reduce the polymers of Fts Z. Molecular docking showed that 202 E bound to the GTP site of Fts Z and inhibited the GTPase activity of Fts Z. Conclusion Compound 202 E is a promising lead for inhibitors of Mycobacterium tuberculosis Fts Z.