Mycobacterium tuberculosis sensitivity to 1-(4-Methylimidazol-5-oyl)-4-(4-dimethyloaminophenyl)thiosemicarbazide and obtainment the resistant mutants by chemical mutation

As part of global efforts to develop an efficient anti-tuberculosis drug, our group is focused on the development of new thiosemicarbazide based compounds as potential anti-Mtb agents. In view of the importance of the thiosemicarbazide moiety, we investigate the anti-Mtb activity of new imidazole-thiosemicarbazide derivatives. The Mtb cultures were preincubated in the sub-inhibitory concentration of compound (0.1xMIC90) by three passages before plating. Then resistant mutants to 1-(4-Methylimidazol-5-oyl)-4-(4-dimethyloaminophenyl)thiosemicarbazide were selected on 7H10/OADC solid media supplemented with 3xMIC90 (97.8 ug/mL) of compound. In this project, we have evaluated the possible effect of compound on Mtb and compare frequency and profile of mutations accumulated in wild type and resistant mutants Mtb strains growing in the presence of 1-(4-Methylimidazol-5-oyl)-4-(4-dimethyloaminophenyl)thiosemicarbazide.

作为开发高效抗结核药物的全球研究计划的一部分，本研究团队致力于开发基于氨基硫脲（thiosemicarbazide）的新型化合物，作为潜在的抗结核分枝杆菌（Mtb）制剂。鉴于氨基硫脲基团的重要性，我们对新型咪唑-氨基硫脲衍生物的抗Mtb活性开展了系统研究。实验中，我们将结核分枝杆菌菌种在受试化合物的亚抑菌浓度（0.1×MIC90）下进行3次传代预培养，随后涂布平板。随后在添加了3倍MIC90（97.8 μg/mL）该化合物的7H10/OADC固体培养基上，筛选出对1-(4-甲基咪唑-5-酰基)-4-(4-二甲氨基苯基)氨基硫脲具有抗性的突变菌株。本项目评估了该受试化合物对结核分枝杆菌的潜在影响，并比较了在1-(4-甲基咪唑-5-酰基)-4-(4-二甲氨基苯基)氨基硫脲存在条件下培养的野生型与抗性突变型结核分枝杆菌菌株中积累的突变的发生频率与突变谱。