Coumarin’s Anti-Quorum Sensing Activity Can Be Enhanced When Combined with Other Plant-Derived Small Molecules

Abstract

Coumarins are class of natural aromatic compounds based on benzopyrones (2H-1-benzopyran-2-ones). They are identified as secondary metabolites in about 150 different plant species. The ability of coumarins to inhibit cell-to-cell communication in bacterial communities (quorum sensing; QS) has been previously described. Coumarin and its derivatives in plant extracts are often found together with other small molecules that show anti-QS properties too. The aim of this study was to find the most effective combinations of coumarins and small plant-derived molecules identified in various plants extracts that inhibit QS in Chromobacterium violaceum ATCC 31532 violacein production bioassay. The coumarin and its derivatives: 7-hydroxycoumarin, 7.8-dihydroxy-4-methylcoumarin, were included in the study. Combinations of coumarins with gamma-octalactone, 4-hexyl-1.3-benzenediol, 3.4.5-trimethoxyphenol and vanillin, previously identified in oak bark (Quercus cortex), and eucalyptus leaves (Eucalyptus viminalis) extracts, were analyzed in a bioassay. When testing two-component compositions, it was shown that 7.8-dihydroxy-4-methylcoumarin, 4-hexyl-1.3-benzendiol, and gamma-octalactone showed a supra-additive anti-QS effect. Combinations of all three molecules resulted in a three- to five-fold reduction in the concentration of each compound needed to achieve EC50 (half maximal effective concentration) against QS in C. violaceum ATCC 31532.

Effect of feeding bioactive compounds identified from plant extracts (4-hexylresorcinol, 7-hydroxycoumarin, and gamma-octalactone) on the productivity and quality of broiler meat

“…In the previous studies, a group of inhibitors of “quorum sensing” – plant metabolites used in this experiment – was identified [ 27 ], their toxicity was evaluated [ 28 ], and effective combinations were determined [ 29 ].…”

Synthetic and Semisynthetic Compounds as Antibacterials Targeting Virulence Traits in Resistant Strains: A Narrative Updated Review

“…Azoles, including pyrazoles, oxadiazoles, and triazoles, have been extensively studied as antifungal agents, but recent studies have shown that they also have antibacterial activity against resistant strains [ 17 ]. Coumarins have been found to inhibit bacterial quorum sensing and motility [ 18 ], while indoles and thiophenes have also shown potential as quorum sensing inhibitors [ 19 ]. Quinolines have been proposed as inhibitors of bacterial type II topoisomerases and have shown activity against multidrug-resistant bacteria [ 20 ].…”

The role of eugenol and ferulic acid as the competitive inhibitors of transcriptional regulator RhlR in P. aeruginosa

“…These results have been achieved by getting the sequence of amino acids from the NCBI databases in FASTA format. Therefore, the in silico methods have made it possible to discover, in various microorganisms, an endless number of QS inhibitory molecules, such as different aromatic compounds, for instance, tyrosol halogenated furanone, coumarins, flavones, and their derivatives [17] , [18] , [19] , [20] , [21] , [22] , [23] . Molecular docking software is currently used for validation by docking and re-docking protocols, either as licensed or free software (e.g., Autodock vina, Autodock4, LeDock, GOLD, Chimera, Mcule, and PyRx) [ 21 , 24 , 25 ].…”

“…This information serves to create point mutations in the QS transcriptional regulators to understand the biological role of amino acids in the protein-ligand binding. Likewise, gene cloning is related to the synthesis of new molecules and increases the affinity to the autoinducer-1 binding domain in the transcriptional regulator of QS obtained, thus attenuating bacterial virulence regulated by QS [19] .…”