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• W2061627549 abstract "Increasing antibiotic resistance urgently requires novel therapeutic options to combat bacterial infections. The anti-virulence therapy selectively intervening with pathogenicity without affecting bacterial viability is such a strategy to overcome resistance. We consider the virulence regulator PqsR as an attractive target in the human pathogen Pseudomonas aeruginosa, and recently discovered the first PqsR antagonists, which, however, suffered from poor aqueous solubility. In this work, the antagonists were structurally modified to become more soluble, and their structure–activity as well as structure–property relationships were studied. A novel promising compound with improved solubility and enhanced anti-virulence activity was discovered (IC50: 3.8 μM, pyocyanin). Our findings emphasize the crucial role of substituents at the 3-position and the carbonyl group at the 4-position for ligand–receptor interactions, and illuminate the way for further optimization of PqsR antagonists as anti-virulence agents." @default.
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• W2061627549 date "2014-05-01" @default.
• W2061627549 modified "2023-10-02" @default.
• W2061627549 title "Optimization of anti-virulence PqsR antagonists regarding aqueous solubility and biological properties resulting in new insights in structure–activity relationships" @default.
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• W2061627549 doi "https://doi.org/10.1016/j.ejmech.2014.04.016" @default.
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