Anti MDR-TB MICs and Cytotoxicity of New Compounds

这一核心是为PO1提供的一项服务，标题为“耐多药结核病药物：靶向细胞壁合成酶”。该核心被设计用来筛选由=化合物开发模块产生的化合物，其中包括分别由Lee博士和Naismith博士提出的项目1和项目2，还包括专门与McNeil博士交互的、项目3的“启动精化循环模块”。我们将获得针对耐多药结核病的2000到3000的MIC值 每年使用两种熟练定义的最低抑菌浓度(MIC)方法，主要是微孔板Alamar蓝法和放射BACTEC 460TB法来确认MIC。具有良好MIC值的化合物将使用时间杀灭法进行杀菌活性测试。 具有有效MIC值的化合物将在哺乳动物细胞系中进行进一步的细胞毒性研究，以获得IC50值，该浓度会导致哺乳动物细胞活力损失50%。细胞毒性测试将在Vero细胞系中进行，并酌情在肿瘤来源的(HepG2)细胞系中进行。选择指数(MIC/IC50)高于10的化合物将被视为“确定的命中”，并将被送往B核心进行研究。 动物模型。在这个核心中收集的信息将被提供给“化合物开发模块”的奈史密斯和李博士，以便能够合成更好的化合物。

This Core is a service for the PO1 entitled "MDR-TB drugs: Targeting Cell Wall synthesis enzymes". The core is designed to screen the compounds generated by the =Compound Development Module", which include Project 1 and Project 2 by Dr. Lee and Dr. Naismith, respectively, and also from the "Priming the Refinement Cycle Module", specifically interacting with Dr. McNeil, Project 3. We will obtain the MIC value against MDR-TB for two to three thousand compounds per annum using two adeptly defined MIC methods, primarily the microplate Alamar blue method and secondly the radiometric BACTEC 460TB method to confirm the MIC. Compounds exhibiting good MIC values will be tested for bactericidal activity using the time-kill method. The compounds that present efficient MIC values will undergo further for cytotoxicity studies in mammalian cell lines to obtain the IC50 values, the concentration causing 50% loss of mammalian cell viability. Cytotoxicity assays will be performed in Vero cell lines and, as appropriate, in tumor-derived (HepG2) cell lines. The Compounds with selective index (MIC/IC50) higher than 10 will be considered "defined hits" and will be sent forward to Core B for studies in the animal model. The information gleaned in this Core will be supplied back to Drs. Naismith and Lee of the "Compound Development Module" to enable the synthesis of better compounds.