Structure-functionality relationship and pharmacological profiles of Pseudomonas aeruginosa alkylquinolone quorum sensing modulators.
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Issue Date
2017-05-31
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Show full item recordAbstract
An important paradigm in anti-infective research is the antivirulence concept. Pathoblockers are compounds which disarm bacteria of their arsenal of virulence factors. PqsR is a transcriptional regulator controlling the production of such factors in Pseudomonas aeruginosa, most prominently pyocyanin. In this work, a series of tool compounds based on the structure of the natural ligand 2-heptyl-4-quinolone (HHQ) were used for probing the structure-functionality relationship. Four different profiles are identified namely agonists, antagonists, inverse agonists and biphasic modulators. Molecular docking studies revealed that each class of the PqsR modulators showed distinctive interactions in the PqsR binding domain. It was found that the substituents in position 3 of the quinolone core act as a switch between the different profiles, according to their ability to donate or accept a hydrogen bond, or form a hydrophobic interaction. Finally, it was shown that only inverse agonists were able to strongly inhibit pyocyanin production.Citation
Structure-functionality relationship and pharmacological profiles of Pseudomonas aeruginosa alkylquinolone quorum sensing modulators. 2017, 15 (21):4620-4630 Org. Biomol. Chem.Affiliation
Helmholtz-Institu für pharmazeutische Forschung Saarland,, Universitätscampus E8.1, 66123 Saarbrücken, Germany.Journal
Organic & biomolecular chemistryPubMed ID
28513746Type
ArticleLanguage
enISSN
1477-0539ae974a485f413a2113503eed53cd6c53
10.1039/c7ob00263g
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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
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