Conformational and docking studies of acyl homoserine lactones as a robust method to investigate bioactive conformations

Soulère, Laurent; Queneau, Yves

doi:10.1016/j.compbiolchem.2019.01.006

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…The luxR model [29] complexed with OHHL described in a previous study was used for docking studies [30]. The binding site was created by selecting residues in the neighborhood of OHHL [31]. A Docking box 15 × 15 × 15 Å center on OHHL was used for docking experiments performed with the genetical algorithm [32] docking engine of the ArgusLab software [33] with default parameters.…”

Section: Molecular Modelingmentioning

confidence: 99%

Biological Evaluation and Docking Studies of New Carbamate, Thiocarbamate, and Hydrazide Analogues of Acyl Homoserine Lactones as Vibrio fischeri-Quorum Sensing Modulators

2020

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A series of carbamate, thiocarbamate, and hydrazide analogues of acylhomoserine lactones (AHLs) were synthesized and their ability to modulate Vibrio fischeri-quorum sensing was evaluated. The compounds in the series exhibit variable side chain length and the possible presence of a diversely substituted phenyl substituent. Biological evaluation on the Vibrio fischeri quorum sensing system revealed that the ethyl substituted carbamate (1) display a weak agonistic activity whereas compounds with longer chain length or benzyl substituents display significant antagonistic activity. The most active compounds in the series were the 4-nitrobenzyl carbamate and thiocarbamate 7 and 11 which exhibited an IC 50 value of about 20 µM. These activities are in the range of other reported of AHL-structurally related quorum sensing (QS) inhibitors. Docking experiments conducted on the LuxR model showed that, compared to the natural ligand OHHL, the additional heteroatom of the carbamate group induces a new hydrogen bond with Tyr70 leading to a different global hydrogen-bond network. Tyr70 is an important residue in the binding site and is strictly conserved in the LuxR family. For the 4-nitrobenzyl carbamate and thiocarbamate analogues, the docking results highlight an additional hydrogen bond between the nitro group and Lys178. For hydrazide analogues, which are deprived of any activity, docking shows that the orientation of the carbonyl group is opposite as compared with the natural ligand, leading to the absence of a H-bond between the C=O with Tyr62. This suggests that, either this later interaction, or the influence of the C=O orientation on the overall ligand conformation, are essential for the biological activity.

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Section: Molecular Modelingmentioning

confidence: 99%

Biological Evaluation and Docking Studies of New Carbamate, Thiocarbamate, and Hydrazide Analogues of Acyl Homoserine Lactones as Vibrio fischeri-Quorum Sensing Modulators

2020

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“…Compounds were drawn with Vega ZZ and 3D structures were generated and minimized using the SP4 force field (Gasteiger charges assignment) [31][32][33]. The LuxR model reported in previous study was employed for docking experiments.…”

Section: Molecular Modelingmentioning

confidence: 99%

(2R)- and (2S)- 2-hydroxy- hexanoyl and octanoyl-l-homoserine lactones: New highly potent Quorum Sensing modulators with opposite activities

Zhang

Jeanneau

Queneau

et al. 2020

Bioorganic Chemistry

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The synthesis and the QS modulation activity of diastereoisomerically pure 2hydroxy acyl-L-homoserine lactones (2-OH-AHLs) are unveiled. (2R)-and (2S)-2-Hydroxy hexanoyl-L-homoserine lactone and 2-hydroxy octanoyl-L-homoserine lactone have been identified as very potent QS agonists and antagonists on the Vibrio fischeri-quorum sensing system with opposite activities depending on the configuration of the carbon atom with the hydroxyl group. Flexible molecular docking showed that the (2R)-OH configuration in the antagonist isomer induces new hydrogen bonds with Tyr70 and Asp79, two importantly conserved residues in the LuxR protein family, while the (2S)-OH agonist configuration exhibits a binding mode comparable to the natural ligand 3-oxo-hexanoyl-L-homoserine lactone (OHHL). For the analogs with long alkyl chain 3a and 3b and aromatic analogs, all are antagonists with no effect of the configuration at C-2.

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1,3-Disubstituted urea derivatives: Synthesis, antimicrobial activity evaluation and in silico studies

Gündüz

Uğur

Güney

et al. 2020

Bioorganic Chemistry

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Conformational and docking studies of acyl homoserine lactones as a robust method to investigate bioactive conformations

Cited by 3 publications

References 29 publications

Biological Evaluation and Docking Studies of New Carbamate, Thiocarbamate, and Hydrazide Analogues of Acyl Homoserine Lactones as Vibrio fischeri-Quorum Sensing Modulators

Biological Evaluation and Docking Studies of New Carbamate, Thiocarbamate, and Hydrazide Analogues of Acyl Homoserine Lactones as Vibrio fischeri-Quorum Sensing Modulators

(2R)- and (2S)- 2-hydroxy- hexanoyl and octanoyl-l-homoserine lactones: New highly potent Quorum Sensing modulators with opposite activities

1,3-Disubstituted urea derivatives: Synthesis, antimicrobial activity evaluation and in silico studies

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