靶点特异性抗结核分枝杆菌药物筛选模型的建立及应用

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目的构建靶点特异性抗结核分枝杆菌药物筛选模型。方法通过诱变剂和诱变条件的考察,确定筛选新生霉素特异性超敏感菌株和超耐药菌株的最佳方案。利用野生株、超敏感菌株与超耐药菌株的活性差异,建立抗结核分枝杆菌药物筛选模型,并对175个化学合成拟抗结核分枝杆菌化合物进行初筛。结果通过UV-Li Cl、微波等诱变方法处理后,得到新生霉素特异性超敏感菌株和超耐药菌株,其MIC值分别为0.4和200 mg·L~(-1)。应用所构建的模型筛选获得一个阳性先导化合物CZQ-06+。结论成功构建了靶点特异性抗结核分枝杆菌药物筛选模型。 Objective To construct a target-specific anti-TB drug screening model. Methods By mutagen and mutagenesis conditions to determine the optimal selection of ningcinomycin-sensitive super-sensitive strains and super-resistant strains of the best program. Based on the differences in the activity of wild-type, super-sensitive and super-resistant strains, a drug screening model of Mycobacterium tuberculosis was established and 175 chemically-synthesized Mycobacterium tuberculosis compounds were screened. Results After treatment with UV-Li Cl, microwave and other mutagenesis methods, the nosocomycin-resistant and ultra-resistant strains were obtained. The MIC values ​​were 0.4 and 200 mg · L -1, respectively. The constructed model was screened to obtain a positive lead compound CZQ-06 +. Conclusion A target-specific anti-TB drug screening model was successfully constructed.
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