Abstract
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.
Highlights
The purpose of this review is to give the state of the art focusing on the use of heterocyclic cores in the design of analogues of N-acyl homoserine lactones (AHLs), which are small molecular signaling molecules used by many Gram-negative bacteria for coordinating their behavior as a function of their population density in a process referred to as Quorum Sensing (QS)
It is a way for bacteria to compete against each other, long-chain AHLs being for example antagonists of the QS of bacteria having short-chain autoinducers
This review highlights the usefulness of heterocyclic chemistry strategies in the design of analogues of acyl homoserine lactones (AHLs)
Summary
Heterocyclic chemistry represents an essential component of organic chemistry, offering high-performance synthetic tools searching for biologically active molecules. When designing molecules endowed with biological activity, it has been noted that certain heterocyclic fragments, of different structure, called bioisosteres, are recognized in a similar way by biological systems. The role of these bioisosteres is to mimic certain patterns present within the biomolecules. The binding of these compounds to receptors induces a change in conformation the therapeutic target [16] due to (a) the geometry of the heterocycle; (b) following electrostatic-type interactions; and (c) by hydrogen bonding For these different interactions to take place, a drug–receptor affinity is necessary. The purpose of this review is to give the state of the art focusing on the use of heterocyclic cores in the design of analogues of N-acyl homoserine lactones (AHLs), which are small molecular signaling molecules used by many Gram-negative bacteria for coordinating their behavior as a function of their population density in a process referred to as Quorum Sensing (QS)
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