Synthesis and biological evaluation of homoserine lactone derived ureas as antagonists of bacterial quorum sensing

Frezza, Marine; Castang, Sandra; Estephane, Jane; Soulère, Laurent; Deshayes, Christian; Chantegrel, Bernard; Nasser, William; Queneau, Yves; Reverchon, Sylvie; Doutheau, Alain

doi:10.1016/j.bmc.2006.03.017

Cited by 80 publications

(62 citation statements)

References 25 publications

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“…Multiple groups have examined the interactions of various LuxR-type receptor proteins, most commonly LuxR, TraR, and LasR, with both natural and nonnatural AHL molecules and have evaluated their subsequent activities. In addition to variations in the length, saturation, and oxidation states of natural AHLs, a plethora of nonnatural AHL analogue substitutions have been synthesized and tested to date, including but not limited to thiolactones (165,166), lactams (167), triazolyldihydrofuranones (168), and urea analogues (169). Analogues have been found that exhibit a range of different activities, including no activity, pure agonism or pure antagonism, partial agonism, and synergistic agonism (167,(170)(171)(172).…”

Section: Inhibition Of Signal Detection Synthetic Signal Analogues Anmentioning

confidence: 99%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

678

556

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SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals.

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Section: Inhibition Of Signal Detection Synthetic Signal Analogues Anmentioning

confidence: 99%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

678

556

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“…[9][10][11][12][13][14][15][16][17][18][19] Structural modifications to the lactone ring, including inversion of stereochemistry, [20] and replacement of the lactone with different carbo-or heterocycles [9][10][11]17,[21][22][23] have been examined to a lesser degree. Four of the most effective AHL-derived antagonists of TraR, LasR, or LuxR reported to date are shown in Scheme 1: the C 7 AHL 4 active against TraR, [13] the 3-oxo-phenylbutanoyl-and phenylbutanoyl HLs (5 and 6) active against LuxR, [14] and the 2-aminophenol analogue of OdDHL 7 active against LasR.…”

Section: Oxo-octanoyl)-l-homoserine Lactone (Oohl 1) and Trar In Thementioning

confidence: 99%

“…[17] (We note, however, that many synthetic AHLs have been tested in racemic form, or their reported stereochemistry was not explicit, which adds additional complexity to this analysis. [9][10][11][13][14][15][16]) Lastly, the roles of acyl group aromaticity and spacer length on ligand activity, specifically in our antagonists 8 and 9, were unknown.…”

Section: Design Of Ahl Library Bmentioning

confidence: 99%

Comparative Analyses of N‐Acylated Homoserine Lactones Reveal Unique Structural Features that Dictate Their Ability to Activate or Inhibit Quorum Sensing

et al. 2008

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Bacterial quorum sensing is mediated by low molecular-weight signals and plays a critical role in both the pathogenesis of infectious disease and beneficial symbioses. There is significant interest in the development of synthetic ligands that can intercept bacterial quorum sensing signals and modulate these outcomes. Here, we report the design and comparative analysis of the effects of ~ 90 synthetic N-acylated homoserine lactones (AHLs) on quorum sensing in three Gram negative bacterial species and a critical examination of the structural features of these ligands that dictate agonistic and antagonistic activity, and selectivity for different R protein targets. These studies have revealed the most comprehensive set of structure-activity relationships to date that direct AHL-mediated quorum sensing and a new set of chemical probes with which to study this complex signaling process. Furthermore, this work provides a foundation on which to design next-generation quorum sensing modulators with improved activities and selectivities.

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“…190,193,198,199 Since the first study of AHL analogues by Eberhard and co-workers, 189 many groups have explored the use of various native and synthetic AHLs to both agonize and antagonize QS-behaviours. [190][191][192][193][194][195][196][197] Some biologically active QS modulators derived from AHLs were also found to suppress biofilm formation in a non-biocidal manner. A selection of these modified AHLs (7-17) are given in Figure 8.…”

Section: Manipulation Of Quorum Sensingmentioning

confidence: 99%