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Heterocyclic Chemistry Applied to the Design of N-Acyl Homoserine Lactone Analogues as Bacterial Quorum Sensing Signals Mimics

N-acyl homoserine lactones (AHLs) are small signaling molecules used by many Gram-negative bacteria for coordinating their behavior as a function of their population density. This process, based on the biosynthesis and the sensing of such molecular signals, and referred to as Quorum Sensing (QS), re...

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Autores principales: Zhang, Qiang, Li, Sizhe, Hachicha, Maha, Boukraa, Mohamed, Soulère, Laurent, Efrit, Mohamed L., Queneau, Yves
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433848/
https://www.ncbi.nlm.nih.gov/pubmed/34500565
http://dx.doi.org/10.3390/molecules26175135
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author Zhang, Qiang
Li, Sizhe
Hachicha, Maha
Boukraa, Mohamed
Soulère, Laurent
Efrit, Mohamed L.
Queneau, Yves
author_facet Zhang, Qiang
Li, Sizhe
Hachicha, Maha
Boukraa, Mohamed
Soulère, Laurent
Efrit, Mohamed L.
Queneau, Yves
author_sort Zhang, Qiang
collection PubMed
description N-acyl homoserine lactones (AHLs) are small signaling molecules used by many Gram-negative bacteria for coordinating their behavior as a function of their population density. This process, based on the biosynthesis and the sensing of such molecular signals, and referred to as Quorum Sensing (QS), regulates various gene expressions, including growth, virulence, biofilms formation, and toxin production. Considering the role of QS in bacterial pathogenicity, its modulation appears as a possible complementary approach in antibacterial strategies. Analogues and mimics of AHLs are therefore biologically relevant targets, including several families in which heterocyclic chemistry provides a strategic contribution in the molecular design and the synthetic approach. AHLs consist of three main sections, the homoserine lactone ring, the central amide group, and the side chain, which can vary in length and level of oxygenation. The purpose of this review is to summarize the contribution of heterocyclic chemistry in the design of AHLs analogues, insisting on the way heterocyclic building blocks can serve as replacements of the lactone moiety, as a bioisostere for the amide group, or as an additional pattern appended to the side chain. A few non-AHL-related heterocyclic compounds with AHL-like QS activity are also mentioned.
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spelling pubmed-84338482021-09-12 Heterocyclic Chemistry Applied to the Design of N-Acyl Homoserine Lactone Analogues as Bacterial Quorum Sensing Signals Mimics Zhang, Qiang Li, Sizhe Hachicha, Maha Boukraa, Mohamed Soulère, Laurent Efrit, Mohamed L. Queneau, Yves Molecules Review N-acyl homoserine lactones (AHLs) are small signaling molecules used by many Gram-negative bacteria for coordinating their behavior as a function of their population density. This process, based on the biosynthesis and the sensing of such molecular signals, and referred to as Quorum Sensing (QS), regulates various gene expressions, including growth, virulence, biofilms formation, and toxin production. Considering the role of QS in bacterial pathogenicity, its modulation appears as a possible complementary approach in antibacterial strategies. Analogues and mimics of AHLs are therefore biologically relevant targets, including several families in which heterocyclic chemistry provides a strategic contribution in the molecular design and the synthetic approach. AHLs consist of three main sections, the homoserine lactone ring, the central amide group, and the side chain, which can vary in length and level of oxygenation. The purpose of this review is to summarize the contribution of heterocyclic chemistry in the design of AHLs analogues, insisting on the way heterocyclic building blocks can serve as replacements of the lactone moiety, as a bioisostere for the amide group, or as an additional pattern appended to the side chain. A few non-AHL-related heterocyclic compounds with AHL-like QS activity are also mentioned. MDPI 2021-08-24 /pmc/articles/PMC8433848/ /pubmed/34500565 http://dx.doi.org/10.3390/molecules26175135 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Zhang, Qiang
Li, Sizhe
Hachicha, Maha
Boukraa, Mohamed
Soulère, Laurent
Efrit, Mohamed L.
Queneau, Yves
Heterocyclic Chemistry Applied to the Design of N-Acyl Homoserine Lactone Analogues as Bacterial Quorum Sensing Signals Mimics
title Heterocyclic Chemistry Applied to the Design of N-Acyl Homoserine Lactone Analogues as Bacterial Quorum Sensing Signals Mimics
title_full Heterocyclic Chemistry Applied to the Design of N-Acyl Homoserine Lactone Analogues as Bacterial Quorum Sensing Signals Mimics
title_fullStr Heterocyclic Chemistry Applied to the Design of N-Acyl Homoserine Lactone Analogues as Bacterial Quorum Sensing Signals Mimics
title_full_unstemmed Heterocyclic Chemistry Applied to the Design of N-Acyl Homoserine Lactone Analogues as Bacterial Quorum Sensing Signals Mimics
title_short Heterocyclic Chemistry Applied to the Design of N-Acyl Homoserine Lactone Analogues as Bacterial Quorum Sensing Signals Mimics
title_sort heterocyclic chemistry applied to the design of n-acyl homoserine lactone analogues as bacterial quorum sensing signals mimics
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433848/
https://www.ncbi.nlm.nih.gov/pubmed/34500565
http://dx.doi.org/10.3390/molecules26175135
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