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dc.contributor.authorThomann, Andreas
dc.contributor.authorBrengel, Christian
dc.contributor.authorBörger, Carsten
dc.contributor.authorKail, Dagmar
dc.contributor.authorSteinbach, Anke
dc.contributor.authorEmpting, Martin
dc.contributor.authorHartmann, Rolf W
dc.date.accessioned2016-11-25T11:41:20Z
dc.date.available2016-11-25T11:41:20Z
dc.date.issued2016-11-21
dc.identifier.citationStructure-Activity Relationships of 2-Sufonylpyrimidines as Quorum-Sensing Inhibitors to Tackle Biofilm Formation and eDNA Release of Pseudomonas aeruginosa. 2016, 11 (22):2522-2533 ChemMedChemen
dc.identifier.issn1860-7187
dc.identifier.pmid27731921
dc.identifier.doi10.1002/cmdc.201600419
dc.identifier.urihttp://hdl.handle.net/10033/620594
dc.description.abstractDrug-resistant Pseudomonas aeruginosa (PA) strains are on the rise, making treatment with current antibiotics ineffective. Hence, circumventing resistance or restoring the activity of antibiotics by novel approaches is of high demand. Targeting the Pseudomonas quinolone signal quorum sensing (PQS-QS) system is an intriguing strategy to abolish PA pathogenicity without affecting the viability of the pathogen. Herein we report the structure-activity relationships of 2-sulfonylpyrimidines, which were previously identified as dual-target inhibitors of the PQS receptor PqsR and the PQS synthase PqsD. The SAR elucidation was guided by a combined approach using ligand efficiency and ligand lipophilicity efficiency to select the most promising compounds. In addition, the most effective inhibitors were rationally modified by the guidance of QSAR using Hansch analyses. Finally, these inhibitors showed the capacity to decrease biofilm mass and extracellular DNA, which are important determinants for antibiotic resistance.
dc.languageENG
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleStructure-Activity Relationships of 2-Sufonylpyrimidines as Quorum-Sensing Inhibitors to Tackle Biofilm Formation and eDNA Release of Pseudomonas aeruginosa.
dc.typeArticleen
dc.contributor.departmentHelmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland Universitätscampus E8.1, 66123 Saarbrücken, Germany.en
dc.identifier.journalChemMedChemen
refterms.dateFOA2017-10-12T00:00:00Z
html.description.abstractDrug-resistant Pseudomonas aeruginosa (PA) strains are on the rise, making treatment with current antibiotics ineffective. Hence, circumventing resistance or restoring the activity of antibiotics by novel approaches is of high demand. Targeting the Pseudomonas quinolone signal quorum sensing (PQS-QS) system is an intriguing strategy to abolish PA pathogenicity without affecting the viability of the pathogen. Herein we report the structure-activity relationships of 2-sulfonylpyrimidines, which were previously identified as dual-target inhibitors of the PQS receptor PqsR and the PQS synthase PqsD. The SAR elucidation was guided by a combined approach using ligand efficiency and ligand lipophilicity efficiency to select the most promising compounds. In addition, the most effective inhibitors were rationally modified by the guidance of QSAR using Hansch analyses. Finally, these inhibitors showed the capacity to decrease biofilm mass and extracellular DNA, which are important determinants for antibiotic resistance.


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