Early Julie V, Casey Allen, Martinez-Grau Maria Angeles, Gonzalez Valcarcel Isabel C, Vieth Michal, Ollinger Juliane, Bailey Mai Ann, Alling Torey, Files Megan, Ovechkina Yulia, Parish Tanya
TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA.
Eli Lilly and Company, Alcobendas, Madrid, Spain.
Antimicrob Agents Chemother. 2016 May 23;60(6):3608-16. doi: 10.1128/AAC.02896-15. Print 2016 Jun.
Mycobacterium tuberculosis is a global pathogen of huge importance which can adapt to several host niche environments in which carbon source availability is likely to vary. We developed and ran a phenotypic screen using butyrate as the sole carbon source to be more reflective of the host lung environment. We screened a library of ∼87,000 small compounds and identified compounds which demonstrated good antitubercular activity against M. tuberculosis grown with butyrate but not with glucose as the carbon source. Among the hits, we identified an oxadiazole series (six compounds) which had specific activity against M. tuberculosis but which lacked cytotoxicity against mammalian cells.
结核分枝杆菌是一种极其重要的全球病原体，它能够适应多种宿主生态位环境，而这些环境中的碳源可用性可能会有所不同。我们开发并进行了一项以丁酸盐作为唯一碳源的表型筛选，以更准确地反映宿主肺部环境。我们筛选了一个约87,000种小分子化合物的文库，并鉴定出了一些化合物，这些化合物对以丁酸盐而非葡萄糖作为碳源培养的结核分枝杆菌表现出良好的抗结核活性。在这些命中的化合物中，我们鉴定出了一个恶二唑系列（六种化合物），它们对结核分枝杆菌具有特异性活性，但对哺乳动物细胞没有细胞毒性。
