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ACS Infect Dis DOI:10.1021/acsinfecdis.6b00206

Identification of Highly Specific Diversity-Oriented Synthesis-Derived Inhibitors of Clostridium difficile.

Publication TypeJournal Article
Year of Publication2017
AuthorsDuvall, JR, Bedard, L, Naylor-Olsen, AM, Manson, AL, Bittker, JA, Sun, W, Fitzgerald, ME, He, Z, Lee, MD, Marie, J-C, Muncipinto, G, Rush, D, Xu, D, Xu, H, Zhang, M, Earl, AM, Palmer, MA, Foley, MA, Vacca, JP, Scherer, CA
JournalACS Infect Dis
Volume3
Issue5
Pages349-359
Date Published2017 May 12
ISSN2373-8227
Abstract

In 2013, the Centers for Disease Control highlighted Clostridium difficile as an urgent threat for antibiotic-resistant infections, in part due to the emergence of highly virulent fluoroquinolone-resistant strains. Limited therapeutic options currently exist, many of which result in disease relapse. We sought to identify molecules specifically targeting C. difficile in high-throughput screens of our diversity-oriented synthesis compound collection. We identified two scaffolds with apparently novel mechanisms of action that selectively target C. difficile while having little to no activity against other intestinal anaerobes; preliminary evidence suggests that compounds from one of these scaffolds target the glutamate racemase. In vivo efficacy data suggest that both compound series may provide lead optimization candidates.

DOI10.1021/acsinfecdis.6b00206
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/28215073?dopt=Abstract

Alternate JournalACS Infect Dis
PubMed ID28215073
PubMed Central IDPMC5509442
Grant ListHHSN272200900018C / AI / NIAID NIH HHS / United States
U19 AI110818 / AI / NIAID NIH HHS / United States