靶点特异性抗结核分枝杆菌药物筛选模型的建立及应用  

The establishment and application of target-specific screening model for anti-Mycobacterium tuberculosis drugs

作　　者：仉蕊 徐威[1] 孙铁民[2] 徐慰倬[1] 

机构地区：[1]沈阳药科大学生命科学与生物制药学院,辽宁沈阳110016 [2]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2016年第8期662-666,共5页Journal of Shenyang Pharmaceutical University

基　　金：辽宁省教育厅高等学校创新团队项目(LT201423);沈阳市科学校术计划项目(F15-199-1-27);国家基础科学人才培养基金项目(J1103606)

摘　　要：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 set up a target-specific anti-Mycobacterium tuberculosis drug screening model.Methods The best method as established to screen the novobiocin supersensitive mutants and superresistant mutants through the screening of mutating agents and mutation conditions. Based on their susceptibility differences,anti-M. tuberculosis screening model as established and 175 chemical synthesis compounds ere screened. Results A novobiocin supersensitive mutant M. phlei SS1 and super-resistant mutant M. phlei RR2 ere isolated through the UV-Li Cl and the microw ave irradiation. Their comparison of MIC ere 0. 4 mg·L^-1and 200 mg·L^-1respectively. Compound CZQ- 06 ＋ as found to inhibit DNA gyrase subunit B selectively. Conclusions The target-specific screening model for anti-M. tuberculosis drugs is established successfully.

关 键 词：草分枝杆菌 新生霉素 DNA回旋酶 筛选模型 

分 类 号：R978.3[医药卫生—药品]