1. Oxadiazoles Have Butyrate-Specific Conditional Activity against Mycobacterium tuberculosis
- Author
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Mai A. Bailey, Maria Angeles Martinez-Grau, Yulia Ovechkina, Allen Casey, Tanya Parish, Isabel C. Gonzalez Valcarcel, Torey Alling, Juliane Ollinger, Michal Vieth, Megan Files, and Julie V. Early
- Subjects
0301 basic medicine ,Tuberculosis ,Cell Survival ,Phenotypic screening ,030106 microbiology ,Antitubercular Agents ,Oxadiazole ,Levofloxacin ,Microbial Sensitivity Tests ,Butyrate ,Biology ,Microbiology ,Small Molecule Libraries ,Mycobacterium tuberculosis ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Species Specificity ,Kanamycin ,Chlorocebus aethiops ,Isoniazid ,medicine ,Animals ,Experimental Therapeutics ,Pharmacology (medical) ,Cytotoxicity ,Vero Cells ,Pathogen ,Pharmacology ,Oxadiazoles ,biology.organism_classification ,medicine.disease ,Culture Media ,High-Throughput Screening Assays ,Glucose ,030104 developmental biology ,Infectious Diseases ,chemistry ,Butyric Acid ,Specific activity ,Metabolic Networks and Pathways - Abstract
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.
- Published
- 2016
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