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dc.contributor.authorLu, Cenbin
dc.contributor.authorKirsch, Benjamin
dc.contributor.authorMaurer, Christine K
dc.contributor.authorde Jong, Johannes C
dc.contributor.authorBraunshausen, Andrea
dc.contributor.authorSteinbach, Anke
dc.contributor.authorHartmann, Rolf W
dc.date.accessioned2014-08-20T09:16:05Z
dc.date.available2014-08-20T09:16:05Z
dc.date.issued2014-05-22
dc.identifier.citationOptimization of anti-virulence PqsR antagonists regarding aqueous solubility and biological properties resulting in new insights in structure-activity relationships. 2014, 79:173-83 Eur J Med Chemen
dc.identifier.issn1768-3254
dc.identifier.pmid24735643
dc.identifier.doi10.1016/j.ejmech.2014.04.016
dc.identifier.urihttp://hdl.handle.net/10033/325005
dc.description.abstractIncreasing 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.
dc.language.isoenen
dc.rightsArchived with thanks to European journal of medicinal chemistryen
dc.titleOptimization of anti-virulence PqsR antagonists regarding aqueous solubility and biological properties resulting in new insights in structure-activity relationships.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Institut für Pharmazeutische Forschung Saarland Campus, Geb. C2.3 Universität des Saarlandes, D-66123 Saarbrücken, Germany.en
dc.identifier.journalEuropean journal of medicinal chemistryen
refterms.dateFOA2018-06-13T01:37:35Z
html.description.abstractIncreasing 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.


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