Structure-Activity Relationships of 2-Sufonylpyrimidines as Quorum-Sensing Inhibitors to Tackle Biofilm Formation and eDNA Release of Pseudomonas aeruginosa.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620594
Title:
Structure-Activity Relationships of 2-Sufonylpyrimidines as Quorum-Sensing Inhibitors to Tackle Biofilm Formation and eDNA Release of Pseudomonas aeruginosa.
Authors:
Thomann, Andreas; Brengel, Christian; Börger, Carsten; Kail, Dagmar; Steinbach, Anke; Empting, Martin ( 0000-0002-0503-5830 ) ; Hartmann, Rolf W
Abstract:
Drug-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.
Affiliation:
Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland Universitätscampus E8.1, 66123 Saarbrücken, Germany.
Citation:
Structure-Activity Relationships of 2-Sufonylpyrimidines as Quorum-Sensing Inhibitors to Tackle Biofilm Formation and eDNA Release of Pseudomonas aeruginosa. 2016, 11 (22):2522-2533 ChemMedChem
Journal:
ChemMedChem
Issue Date:
21-Nov-2016
URI:
http://hdl.handle.net/10033/620594
DOI:
10.1002/cmdc.201600419
PubMed ID:
27731921
Type:
Article
ISSN:
1860-7187
Appears in Collections:
publications of the department drug design and optimization (HIPS]DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorThomann, Andreasen
dc.contributor.authorBrengel, Christianen
dc.contributor.authorBörger, Carstenen
dc.contributor.authorKail, Dagmaren
dc.contributor.authorSteinbach, Ankeen
dc.contributor.authorEmpting, Martinen
dc.contributor.authorHartmann, Rolf Wen
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.en
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

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