Journal article
Real Way to Target Gram-Negative Pathogens: Discovery of a Novel Helicobacter pylori Antibiotic Class
Journal of medicinal chemistry, Vol.68(10), pp.10128-10138
05/22/2025
DOI: 10.1021/acs.jmedchem.5c00112
PMCID: PMC12105023
PMID: 40163413
Appears in UI Libraries Support Open Access
Abstract
In an era of escalating antibiotic resistance, there is a pressing need for innovative strategies to develop novel antibiotics. Gram-negative bacteria, characterized by their robust dual-membrane, are intrinsically resistant to a wide range of antibiotics and can readily develop new resistances. Members of this bacterial class comprise numerous pathogenic organisms, including the primary cause of gastric cancer, Helicobacter pylori. In this study, we used the Giga-sized collection of theoretical molecules inside Enamine's REAL Space to identify inhibitors for H. pylori glutamate racemase. These compounds displayed a diverse range of activity in preventing H. pylori growth, with our most potent hits capable of selective full growth inhibition for metronidazole and clarithromycin resistant H. pylori strains. Alongside the introduction of a novel antibiotic class for this carcinogenic pathogen, our unique implementation of REAL Space holds great promise for Gram-negative antibiotic development as a whole.
Details
- Title: Subtitle
- Real Way to Target Gram-Negative Pathogens: Discovery of a Novel Helicobacter pylori Antibiotic Class
- Creators
- Jonah Pascal Propp - University of IowaDamien Oz Castor - Univ Iowa Roy J, Carver Coll Med, Dept Biochem, Iowa City, IA 52242 USAM. Ashley Spies - Univ Iowa, Coll Pharm, Dept Pharmaceut Sci & Expt Therapeut, Iowa City, IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- Journal of medicinal chemistry, Vol.68(10), pp.10128-10138
- DOI
- 10.1021/acs.jmedchem.5c00112
- PMID
- 40163413
- PMCID
- PMC12105023
- NLM abbreviation
- J Med Chem
- ISSN
- 0022-2623
- eISSN
- 1520-4804
- Publisher
- American Chemical Society
- Number of pages
- 11
- Grant note
- R01-GM09737; R01-GM138471 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Electronic publication date
- 03/31/2025
- Date published
- 05/22/2025
- Academic Unit
- Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984811224202771
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