# Real Way to Target Gram-Negative Pathogens: Discovery of a Novel Helicobacter pylori Antibiotic Class

**Authors:** Jonah Pascal Propp, Damien Oz Castor, M. Ashley Spies

PMC · DOI: 10.1021/acs.jmedchem.5c00112 · 2025-03-31

## TL;DR

Researchers discovered a new class of antibiotics targeting Helicobacter pylori, a bacteria linked to gastric cancer, using a large database of theoretical molecules.

## Contribution

A novel antibiotic class for H. pylori and a new application of REAL Space for Gram-negative antibiotic development.

## Key findings

- Compounds from Enamine’s REAL Space inhibited H. pylori growth effectively.
- The most potent compounds worked against metronidazole and clarithromycin-resistant strains.
- The method shows promise for developing antibiotics against other Gram-negative bacteria.

## 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.

## Linked entities

- **Diseases:** gastric cancer (MONDO:0001056)
- **Species:** Helicobacter pylori (taxon 210)

## Full-text entities

- **Diseases:** carcinogenic (MESH:D011230), gastric cancer (MESH:D013274)
- **Chemicals:** metronidazole (MESH:D008795), Gram (-), clarithromycin (MESH:D017291)
- **Species:** Helicobacter pylori (species) [taxon 210], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12105023/full.md

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Source: https://tomesphere.com/paper/PMC12105023