Exploring the chemical space of ureidothiophene-2-carboxylic acids as inhibitors of the quorum sensing enzyme PqsD from Pseudomonas aeruginosa.

2.50
Hdl Handle:
http://hdl.handle.net/10033/556202
Title:
Exploring the chemical space of ureidothiophene-2-carboxylic acids as inhibitors of the quorum sensing enzyme PqsD from Pseudomonas aeruginosa.
Authors:
Sahner, J Henning; Empting, Martin; Kamal, Ahmed; Weidel, Elisabeth; Groh, Matthias; Börger, Carsten; Hartmann, Rolf W
Abstract:
Pseudomonas aeruginosa employs a quorum sensing (QS) communication system that makes use of small diffusible molecules. Among other effects, the QS system coordinates the formation of biofilm which decisively contributes to difficulties in the therapy of Pseudomonas infections. The present work deals with the structure-activity exploration of ureidothiophene-2-carboxylic acids as inhibitors of PqsD, a key enzyme in the biosynthetic pathway of signal molecules in the Pseudomonas QS system. We describe an improvement of the inhibitory activity by successfully combining features from two different PqsD inhibitor classes. Furthermore the functional groups, which are responsible for the inhibitory potency, were identified. Moreover, the inability of the new inhibitors, to prevent signal molecule formation in whole cell assays, is discussed.
Affiliation:
Pharmaceutical and Medicinal Chemistry, Saarland University & Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Design and Optimization, Campus C2 3, 66123 Saarbrücken, Germany.
Citation:
Exploring the chemical space of ureidothiophene-2-carboxylic acids as inhibitors of the quorum sensing enzyme PqsD from Pseudomonas aeruginosa. 2015, 96:14-21 Eur J Med Chem
Journal:
European journal of medicinal chemistry
Issue Date:
26-May-2015
URI:
http://hdl.handle.net/10033/556202
DOI:
10.1016/j.ejmech.2015.04.007
PubMed ID:
25874327
Type:
Article
Language:
en
ISSN:
1768-3254
Appears in Collections:
publications of the department drug design and optimization (HIPS]DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorSahner, J Henningen
dc.contributor.authorEmpting, Martinen
dc.contributor.authorKamal, Ahmeden
dc.contributor.authorWeidel, Elisabethen
dc.contributor.authorGroh, Matthiasen
dc.contributor.authorBörger, Carstenen
dc.contributor.authorHartmann, Rolf Wen
dc.date.accessioned2015-06-03T12:40:11Zen
dc.date.available2015-06-03T12:40:11Zen
dc.date.issued2015-05-26en
dc.identifier.citationExploring the chemical space of ureidothiophene-2-carboxylic acids as inhibitors of the quorum sensing enzyme PqsD from Pseudomonas aeruginosa. 2015, 96:14-21 Eur J Med Chemen
dc.identifier.issn1768-3254en
dc.identifier.pmid25874327en
dc.identifier.doi10.1016/j.ejmech.2015.04.007en
dc.identifier.urihttp://hdl.handle.net/10033/556202en
dc.description.abstractPseudomonas aeruginosa employs a quorum sensing (QS) communication system that makes use of small diffusible molecules. Among other effects, the QS system coordinates the formation of biofilm which decisively contributes to difficulties in the therapy of Pseudomonas infections. The present work deals with the structure-activity exploration of ureidothiophene-2-carboxylic acids as inhibitors of PqsD, a key enzyme in the biosynthetic pathway of signal molecules in the Pseudomonas QS system. We describe an improvement of the inhibitory activity by successfully combining features from two different PqsD inhibitor classes. Furthermore the functional groups, which are responsible for the inhibitory potency, were identified. Moreover, the inability of the new inhibitors, to prevent signal molecule formation in whole cell assays, is discussed.en
dc.language.isoenen
dc.titleExploring the chemical space of ureidothiophene-2-carboxylic acids as inhibitors of the quorum sensing enzyme PqsD from Pseudomonas aeruginosa.en
dc.typeArticleen
dc.contributor.departmentPharmaceutical and Medicinal Chemistry, Saarland University & Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Design and Optimization, Campus C2 3, 66123 Saarbrücken, Germany.en
dc.identifier.journalEuropean journal of medicinal chemistryen

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