Identification of Highly Specific Diversity-Oriented Synthesis-Derived Inhibitors of Clostridium difficile.
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.
|Year of Publication||
ACS Infect Dis
2017 05 12
|PubMed Central ID||
HHSN272200900018C / AI / NIAID NIH HHS / United States
U19 AI110818 / AI / NIAID NIH HHS / United States