{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T13:30:32Z","timestamp":1771248632320,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>New N-benzoyl-l-homoserine lactone derivatives bearing a meta-fluorosulfonyl or a meta-methylsulfonyl group have been designed, synthesized and evaluated as quorum sensing (QS) inhibitors. Docking simulations involving the structure of several targeted LuxR-type receptors suggested that a sulfonyl substituent on the benzene ring can trigger interactions within the binding site, possibly consistent with either covalent SuFEx reaction targeting a tyrosine residue or competitive interaction with additional hydrogen bonding. Biological evaluation of the two meta- methyl or fluorosulfonyl-benzoyl acylhomoserine lactone (AHL) analogs as LuxR-regulated quorumsensing inhibitors showed a significant effect for the fluorosulfonyl derivative with an IC50 value of 15 \u00b1 2 \u00b5M, while the methylsulfonyl was found to be a weak inhibitor. The stability of the fluorosulfonyl derivative was confirmed by kinetic studies based on 19F NMR experiments. Investigations dedicated to defining the mechanism of action, either covalent or competitive, were achieved through experiments including inhibition assays without or with pre-incubation in the bacterial medium, and LC\/MS analysis with the ExpR protein. The results strongly suggest that the type of inhibition is a competitive one.<\/jats:p>","DOI":"10.3390\/biom16020305","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T12:37:28Z","timestamp":1771245448000},"page":"305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure-Aided Design of a LuxR-Type Quorum Sensing SuFEx-Based Potential Inhibitor: Covalent or Competitive Inhibition?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0488-550X","authenticated-orcid":false,"given":"Laurent","family":"Soul\u00e8re","sequence":"first","affiliation":[{"name":"INSA LYON, CPE Lyon, Institut de Chimie et Biochimie Mol\u00e9culaires et Supramol\u00e9culaires (ICBMS), Universite de Lyon 1, CNRS, UMR 5246, B\u00e2timent Lederer, 1 rue Victor Grignard, F-69622 Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0478-3474","authenticated-orcid":false,"given":"Sylvie","family":"Reverchon","sequence":"additional","affiliation":[{"name":"INSA LYON, Laboratoire Microbiologie, Adaptation et Pathog\u00e9nie (MAP), Universite de Lyon 1, CNRS, UMR 5240, B\u00e2timent Pasteur, 11 Avenue Jean Capelle, F-69621 Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Baude","sequence":"additional","affiliation":[{"name":"INSA LYON, Laboratoire Microbiologie, Adaptation et Pathog\u00e9nie (MAP), Universite de Lyon 1, CNRS, UMR 5240, B\u00e2timent Pasteur, 11 Avenue Jean Capelle, F-69621 Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Chefdeville","sequence":"additional","affiliation":[{"name":"Institut de Chimie et Biochimie Mol\u00e9culaires et Supramol\u00e9culaires (ICBMS), Centre Commun de RMN (CCRMN), Universit\u00e9 Claude Bernard Lyon 1, B\u00e2timent Lederer, 1 rue V. Grignard, F-69622 Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Vauchez","sequence":"additional","affiliation":[{"name":"Institut de Chimie et Biochimie Mol\u00e9culaires et Supramol\u00e9culaires (ICBMS), Centre Commun de la Spectrom\u00e9trie de Masse (CCSM), B\u00e2timent Edgar Lederer, 1 rue Victor Grignard, F-69622 Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4052-061X","authenticated-orcid":false,"given":"Yves","family":"Queneau","sequence":"additional","affiliation":[{"name":"INSA LYON, CPE Lyon, Institut de Chimie et Biochimie Mol\u00e9culaires et Supramol\u00e9culaires (ICBMS), Universite de Lyon 1, CNRS, UMR 5246, B\u00e2timent Lederer, 1 rue Victor Grignard, F-69622 Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9848-3597","authenticated-orcid":false,"given":"William","family":"Nasser","sequence":"additional","affiliation":[{"name":"INSA LYON, Laboratoire Microbiologie, Adaptation et Pathog\u00e9nie (MAP), Universite de Lyon 1, CNRS, UMR 5240, B\u00e2timent Pasteur, 11 Avenue Jean Capelle, F-69621 Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1007\/s00203-021-02381-9","article-title":"N-acyl homoserine lactone molecules assisted quorum sensing: Effects consequences and monitoring of bacteria talking in real life","volume":"203","author":"Acet","year":"2021","journal-title":"Arch. 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