Design, synthesis and evaluation of N-aryl-glyoxamide derivatives as structurally novel bacterial quorum sensing inhibitors

Pseudomonas aeruginosa is recognised as a major aetiological agent of nosocomial infections, which are associated with multiple-antibiotic resistance. Among many of its important virulence factors is its ability to form biofilms on the surfaces of implantable medical devices and to produce toxic metabolites, pyocyanin, via an intercellular cell density-dependent signalling system of communication. In this study, poly (ε-lysine) dendrons composed of increasingly branching generations were synthesised, characterised, and examined for their effects on virulence factor production in P. aeruginosa. The results show that these hyperbranched poly (ε-lysine) dendrons, in particular the 3rd generation, can increase the efficacy of a conventional antibiotic, ciprofloxacin, and reduce pyocyanin production, with marginal effects on the rate of bacterial replication, suggesting that the observed effects are not due to dendron toxicity. Furthermore, dendron and ciprofloxacin coadministration was identified as the most effective strategy which highlights the potential of peptide-based dendrons as quorum sensing inhibitors.

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Polyphenols from Salix tetrasperma Impair Virulence and Inhibit Quorum Sensing of Pseudomonas aeruginosa

Molecules ◽

10.3390/molecules25061341 ◽

2020 ◽

Vol 25 (6) ◽

pp. 1341 ◽

Cited By ~ 4

Author(s):

Islam Mostafa ◽

Hisham A. Abbas ◽

Mohamed L. Ashour ◽

Abdelaziz Yasri ◽

Assem M. El-Shazly ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Secondary Metabolites ◽

Bacterial Resistance ◽

Stem Bark ◽

Dependent Manner ◽

Active Components ◽

Quorum Sensing Inhibitors ◽

Bacterial Quorum Sensing ◽

Bacterial Quorum

Bacterial resistance represents one of the emerging obstacles in plants, animals, and humans that impairs treatment with antibacterial agents. Targeting of the bacterial quorum sensing system is one of the strategies to overcome this problem. Recently, research has been focused on natural and food components which can function as quorum sensing inhibitors. In this study, a methanol extract from Salix tetrasperma stem bark was phytochemically profiled by LC-MS analysis. This resulted in the identification of 38 secondary metabolites with (epi)catechin-(epi)catechin, epicatechin, tremulacin, salicortin, and trichocarposide as the major constituents. The extracts of both stem bark and the previously profiled flower of S. tetrasperma were tested for anti-quorum sensing activity in a common and widely distributed pathogen Pseudomonas aeruginosa. The natural products inhibited swimming and swarming motilities, as well as proteolytic and hemolytic activities in a dose-dependent manner. Molecular docking of the constituents from both extracts against the quorum sensing controlling systems Lasl/LasR, rhll/rhlR, and PQS/MvfR showed that epicatechin, (epi)catechin-(epi)catechin, p-hydroxy benzoyl galloyl glucose, p-hydroxy benzoyl protocatechuic acid glucose, and caffeoylmalic acid could be the main active components. This study supports the importance of secondary metabolites, especially polyphenols, as quorum sensing inhibitors.

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