Journal article
Development of 1,2,4-Oxadiazole Antimicrobial Agents to Treat Enteric Pathogens within the Gastrointestinal Tract
ACS Omega, Vol.7(8), pp.6737-6759
2022
Abstract
Colonization of the gastrointestinal (GI) tract with pathogenic bacteria is an important risk factor for the development of certain potentially severe and life-threatening healthcare-associated infections, yet efforts to develop effective decolonization agents have been largely unsuccessful thus far. Herein, we report modification of the 1,2,4-oxadiazole class of antimicrobial compounds with poorly permeable functional groups in order to target bacterial pathogens within the GI tract. We have identified that the quaternary ammonium functionality of analogue 26a results in complete impermeability in Caco-2 cell monolayers while retaining activity against GI pathogens Clostridioides difficile and multidrug-resistant (MDR) Enterococcus faecium. Low compound recovery levels after oral administration in rats were observed, which suggests that the analogues may be susceptible to degradation or metabolism within the gut, highlighting a key area for optimization in future efforts. This study demonstrates that modified analogues of the 1,2,4-oxadiazole class may be potential leads for further development of colon-targeted antimicrobial agents.
Details
- Title
- Development of 1,2,4-Oxadiazole Antimicrobial Agents to Treat Enteric Pathogens within the Gastrointestinal Tract
- Authors/Creators
- N.P. Pitcher (Author/Creator) - Monash UniversityJ.R. Harjani (Author/Creator) - Monash UniversityY. Zhao (Author/Creator) - Monash UniversityJ. Jin (Author/Creator) - Monash UniversityD.R. Knight (Author/Creator) - Queen Elizabeth II Medical CentreL. Li (Author/Creator) - Peter Doherty InstituteP. Putsathit (Author/Creator) - Queen Elizabeth II Medical CentreT.V. Riley (Author/Creator) - Queen Elizabeth II Medical CentreG.P. Carter (Author/Creator) - Peter Doherty InstituteJ.B. Baell (Author/Creator) - Nanjing Tech University
- Publication Details
- ACS Omega, Vol.7(8), pp.6737-6759
- Publisher
- American Chemical Society
- Identifiers
- 991005545256807891
- Copyright
- © 2022 The Authors.
- Murdoch Affiliation
- School of Medical, Molecular and Forensic Sciences
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.23 Antibiotics & Antimicrobials
- 1.23.173 MRSA and VRE
- Web Of Science research areas
- Chemistry, Multidisciplinary
- ESI research areas
- Chemistry