Document Type

Journal Article

Publication Title

ACS Omega

Volume

7

Issue

8

First Page

6737

Last Page

6759

Publisher

ACS

School

School of Medical and Health Sciences

RAS ID

44323

Funders

The National Health and Medical Research Council of Australia (2012–2016 Senior Research Fellowship #1020411, 2017-Principal Research Fellowship #1117602, ideas grant GNT1185213), The Australian Translational Medicinal Chemistry Facility (ATMCF), Monash Institute of Pharmaceutical Sciences (MIPS), Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) program via Therapeutic Innovation Australia (TIA).

Comments

Pitcher, N. P., Harjani, J. R., Zhao, Y., Jin, J., Knight, D. R., Li, L., ... & Baell, J. B. (2022). Development of 1, 2, 4-Oxadiazole Antimicrobial Agents to Treat Enteric Pathogens within the Gastrointestinal Tract. ACS omega, 7, 8, 6737–6759. https://doi.org/10.1021/acsomega.1c06294

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.

DOI

10.1021/acsomega.1c06294

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Research Themes

Health

Priority Areas

Prevention, detection and management of cancer and other chronic diseases

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