Anti MDR-TB MICs and Cytotoxicity of New Compounds

新化合物的抗耐多药结核病 MIC 和细胞毒性

• 批准号: 6735405
• 负责人: DELPHI CHATTERJEE
• 金额: $ 12.52万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6735405
• 关键词: Mycobacterium tuberculosis; antitubercular agents; bacterial proteins; biomedical facility; bioterrorism /chemical warfare; cell line; cell wall; cytotoxicity; drug design /synthesis /production; drug screening /evaluation; enzyme inhibitors; multidrug resistance

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.

该核心是标题为“ MDR-TB药物：靶向细胞壁合成酶”的PO1的服务。该核心旨在筛选由=复合开发模块生成的化合物”，其中包括李博士和Naismith博士的项目1和项目2，也包括从“启动改进周期模块”中的“启动改进循环模块”，特别是与项目3的麦克尼尔博士相互作用。 每年使用两种熟练定义的MIC方法的化合物，主要是微型板alamar蓝方法，其次是辐射射频BACTEC 460TB方法来确认MIC。表现出良好MIC值的化合物将使用Time-Kill方法测试杀菌活性。 在哺乳动物细胞系中的细胞毒性研究以获得IC50值，浓度导致50％的哺乳动物细胞活力丧失，将进一步进行有效的MIC值的化合物。细胞毒性测定将在Vero细胞系中进行，并在适当的情况下在肿瘤衍生的（HEPG2）细胞系中进行。选择性指数（MIC/IC50）高于10的化合物将被视为“定义的命中”，并将被发送到Core B，以进行研究 动物模型。该核心收集的信息将提供给DRS。 “复合开发模块”的Naismith和Lee能够合成更好的化合物。