Natural‐Product‐Inspired Aminoepoxybenzoquinones Kill Members of the Gram‐Negative Pathogen Salmonella by Attenuating Cellular Stress Response
| Autor: | Franziska A. Mandl, Stephan A. Sieber, Klaus Richter, Ilke Ugur, Christian Fetzer, Iris Antes, Jan Vomacka, Volker C. Kirsch, Thilo M. Fuchs, Sabine Schneider, Elena Kunold |
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| Rok vydání: | 2016 |
| Předmět: |
Salmonella typhimurium
0301 basic medicine Salmonella Gram-negative bacteria Microbial Sensitivity Tests Molecular Dynamics Simulation medicine.disease_cause 01 natural sciences Catalysis Microbiology 03 medical and health sciences chemistry.chemical_compound Cellular stress response Benzoquinones medicine Pathogen Biological Products Natural product Molecular Structure biology 010405 organic chemistry Pathogenic bacteria General Chemistry biology.organism_classification Anti-Bacterial Agents 0104 chemical sciences 030104 developmental biology chemistry Antibacterial activity Bacteria |
| Zdroj: | Angewandte Chemie International Edition. 55:14852-14857 |
| ISSN: | 1521-3773 1433-7851 |
| Popis: | Gram-negative bacteria represent a challenging task for antibacterial drug discovery owing to their impermeable cell membrane and restricted uptake of small molecules. We herein describe the synthesis of natural-product-derived epoxycyclohexenones and explore their antibiotic activity against several pathogenic bacteria. A compound with activity against Salmonella Typhimurium was identified, and the target enzymes were unraveled by quantitative chemical proteomics. Importantly, two protein hits were linked to bacterial stress response, and corresponding assays revealed an elevated susceptibility to reactive oxygen species upon compound treatment. The consolidated inhibition of these targets provides a rationale for antibacterial activity and highlights epoxycyclohexenones as natural product scaffolds with suitable properties for killing Gram-negative Salmonella. |
| Databáze: | OpenAIRE |
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