{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T21:40:59Z","timestamp":1781127659955,"version":"3.54.1"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,1,28]],"date-time":"2018-01-28T00:00:00Z","timestamp":1517097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N501852\/1"],"award-info":[{"award-number":["MR\/N501852\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Engineering and Physical Sciences Research Council","award":["EP\/M027333\/1"],"award-info":[{"award-number":["EP\/M027333\/1"]}]},{"name":"Colciencias and Universidad del Valle"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis, wound and nosocomial infections, posing a serious burden to public health, due to its antibiotic resistance. The P. aeruginosa Pseudomonas Quinolone System (pqs) quorum sensing system, driven by the activation of the transcriptional regulator, PqsR (MvfR) by alkylquinolone (AQ) signal molecules, is a key player in the regulation of virulence and a potential target for the development of novel antibacterial agents. In this study, we performed in silico docking analysis, coupled with screening using a P. aeruginosa mCTX::PpqsA-lux chromosomal promoter fusion, to identify a series of new PqsR antagonists. The hit compounds inhibited pyocyanin and alkylquinolone signal molecule production in P. aeruginosa PAO1-L and PA14 strains. The inhibitor Ia, which showed the highest activity in PA14, reduced biofilm formation in PAO1-L and PA14, increasing their sensitivity to tobramycin. Furthermore, the hepatic and plasma stabilities for these compounds were determined in both rat and human in vitro microsomal assays, to gain a further understanding of their therapeutic potential. This work has uncovered a new class of P. aeruginosa PqsR antagonists with potential for hit to lead optimisation in the search for quorum sensing inhibitors for future anti-infective drug discovery programs.<\/jats:p>","DOI":"10.3390\/molecules23020257","type":"journal-article","created":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T07:46:20Z","timestamp":1517211980000},"page":"257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6730-2543","authenticated-orcid":false,"given":"Fadi","family":"Soukarieh","sequence":"first","affiliation":[{"name":"School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Vico Oton","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fr\u00e9d\u00e9ric","family":"Dubern","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice","family":"Gomes","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Halliday","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"De Pilar Crespo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Universidad del Valle and Departamento of Biomedical Sciences, Universidad Santiago de Cali, Cali AA 760035, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Ram\u00edrez-Prada","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Universidad del Valle, Cali AA 25360, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Braulio","family":"Insuasty","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Universidad del Valle, Cali AA 25360, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Abonia","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Universidad del Valle, Cali AA 25360, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9451-3063","authenticated-orcid":false,"given":"Jairo","family":"Quiroga","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Universidad del Valle, Cali AA 25360, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5079-3622","authenticated-orcid":false,"given":"Stephan","family":"Heeb","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Williams","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3046-137X","authenticated-orcid":false,"given":"Michael","family":"Stocks","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4585-7385","authenticated-orcid":false,"given":"Miguel","family":"C\u00e1mara","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1001\/jama.2016.11764","article-title":"Antimicrobial Resistance","volume":"316","author":"Marston","year":"2016","journal-title":"JAMA"},{"key":"ref_2","first-page":"277","article-title":"The antibiotic resistance crisis: Part 1: Causes and threats","volume":"40","author":"Ventola","year":"2015","journal-title":"Pharm. 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