Abstract
Novel pyrone-derived quorum sensing (QS) ligands to inhibit the binding of OdDHL to the LasR of Pseudomonas aeruginosa were designed, synthesized and evaluated. Among the analogs, the most potent compound 8 exhibited strong in vitro inhibitory activities against biofilm formation and down-regulated OdDHL/LasR-associated genes by 35-67%. The binding mode of 8 in silico was highly similar to that of the crystal ligand OdDHL in the active site of LasR.
Keywords:
Biofilm inhibition; Pseudomonas aeruginosa; Pyrone; Quorum sensing.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Butyrolactone / analogs & derivatives
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4-Butyrolactone / metabolism
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology*
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Bacterial Proteins / metabolism*
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Biofilms / drug effects*
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Homoserine / analogs & derivatives
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Homoserine / metabolism
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Humans
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Molecular Docking Simulation
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Pseudomonas Infections / drug therapy
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Pseudomonas Infections / microbiology
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Pseudomonas Infections / prevention & control
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Pseudomonas aeruginosa / drug effects*
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Pseudomonas aeruginosa / physiology
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Pyrones / chemistry
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Pyrones / pharmacology*
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Quorum Sensing / drug effects*
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Structure-Activity Relationship
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Trans-Activators / metabolism*
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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LasR protein, Pseudomonas aeruginosa
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N-(3-oxododecanoyl)homoserine lactone
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Pyrones
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Trans-Activators
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Homoserine
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4-Butyrolactone