5lir

Publication Abstract from PubMed

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.

Natural-Product-Inspired Aminoepoxybenzoquinones Kill Members of the Gram-Negative Pathogen Salmonella by Attenuating Cellular Stress Response.,Mandl FA, Kirsch VC, Ugur I, Kunold E, Vomacka J, Fetzer C, Schneider S, Richter K, Fuchs TM, Antes I, Sieber SA Angew Chem Int Ed Engl. 2016 Nov 14;55(47):14852-14857. doi:, 10.1002/anie.201607338. Epub 2016 Oct 26. PMID:27782347^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.