Oxadiazoles Have Butyrate-Specific Conditional Activity against Mycobacterium tuberculosis

  • Antimicrob Agents Chemother. 2016 May 23;60(6):3608-16. doi: 10.1128/AAC.02896-15.
Julie V Early  1 ,  Allen Casey  1 ,  Maria Angeles Martinez-Grau  2 ,  Isabel C Gonzalez Valcarcel  3 ,  Michal Vieth  3 ,  Juliane Ollinger  1 ,  Mai Ann Bailey  1 ,  Torey Alling  1 ,  Megan Files  1 ,  Yulia Ovechkina  1 ,  Tanya Parish  4
Affiliations
  • 1. TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA.
  • 2. Eli Lilly and Company, Alcobendas, Madrid, Spain.
  • 3. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
  • 4. TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA [email protected].
PMID: 27044545 DOI: 10.1128/AAC.02896-15
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.

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