Structure-functionality relationship and pharmacological profiles of Pseudomonas aeruginosa alkylquinolone quorum sensing modulators.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractAn 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.
CitationStructure-functionality relationship and pharmacological profiles of Pseudomonas aeruginosa alkylquinolone quorum sensing modulators. 2017, 15 (21):4620-4630 Org. Biomol. Chem.
AffiliationHelmholtz-Institu für pharmazeutische Forschung Saarland,, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
JournalOrganic & biomolecular chemistry
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR).
- Authors: Ilangovan A, Fletcher M, Rampioni G, Pustelny C, Rumbaugh K, Heeb S, Cámara M, Truman A, Chhabra SR, Emsley J, Williams P
- Issue date: 2013
- In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa.
- Authors: Soukarieh F, Vico Oton E, Dubern JF, Gomes J, Halliday N, de Pilar Crespo M, Ramírez-Prada J, Insuasty B, Abonia R, Quiroga J, Heeb S, Williams P, Stocks MJ, Cámara M
- Issue date: 2018 Jan 28
- Discovery of antagonists of PqsR, a key player in 2-alkyl-4-quinolone-dependent quorum sensing in Pseudomonas aeruginosa.
- Authors: Lu C, Kirsch B, Zimmer C, de Jong JC, Henn C, Maurer CK, Müsken M, Häussler S, Steinbach A, Hartmann RW
- Issue date: 2012 Mar 23
- Anti-PqsR compounds as next-generation antibacterial agents against Pseudomonas aeruginosa: A review.
- Authors: Soheili V, Tajani AS, Ghodsi R, Bazzaz BSF
- Issue date: 2019 Jun 15
- Dynorphin activates quorum sensing quinolone signaling in Pseudomonas aeruginosa.
- Authors: Zaborina O, Lepine F, Xiao G, Valuckaite V, Chen Y, Li T, Ciancio M, Zaborin A, Petrof EO, Turner JR, Rahme LG, Chang E, Alverdy JC
- Issue date: 2007 Mar