Abstract:
:Clostridioides difficile infection (CDI) causes serious and sometimes fatal symptoms like diarrhea and pseudomembranous colitis. Although antibiotics for CDI exist, they are either expensive or cause recurrence of the infection due to their altering the colonic microbiota, which is necessary to suppress the infection. Here, we leverage a class of known membrane-targeting compounds that we previously showed to have broad inhibitory activity across multiple Clostridioides difficile strains while preserving the microbiome to develop an efficacious agent. A new series of salicylanilides was synthesized, and the most potent analog was selected through an in vitro inhibitory assay to evaluate its pharmacokinetic parameters and potency in a CDI mouse model. The results revealed reduced recurrence of CDI and diminished disturbance of the microbiota in mice compared to standard-of-care vancomycin, thus paving the way for novel therapy that can potentially target the cell membrane of C. difficile to minimize relapse in the recovering patient.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Blake S,Thanissery R,Rivera AJ,Hixon MS,Lin M,Theriot CM,Janda KDdoi
10.1021/acs.jmedchem.0c00123subject
Has Abstractpub_date
2020-07-09 00:00:00pages
6898-6908issue
13eissn
0022-2623issn
1520-4804journal_volume
63pub_type
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