{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:31:52Z","timestamp":1789079512668,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development Fund, University of Zagreb"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Inhibiting quorum sensing (QS), a central communication system, is a promising strategy to combat bacterial pathogens without antibiotics. Here, we designed novel hybrid compounds targeting the PQS (Pseudomonas quinolone signal)-dependent quorum sensing (QS) of Pseudomonas aeruginosa that is one of the multidrug-resistant and highly virulent pathogens with urgent need of new antibacterial strategies. We synthesized 12 compounds using standard procedures to combine halogen-substituted anthranilic acids with 4-(2-aminoethyl\/4-aminobuthyl)amino-7-chloroquinoline, linked via 1,3,4-oxadiazole. Their antibiofilm activities were first pre-screened using Gram-negative Chromobacterium violaceum-based reporter, which identified compounds 15\u201319 and 23 with the highest anti-QS and minimal bactericidal effects in a single experiment. These five compounds were then evaluated against P. aeruginosa PAO1 to assess their ability to prevent biofilm formation, eradicate pre-formed biofilms, and inhibit virulence using pyocyanin as a representative marker. Compound 15 displayed the most potent antibiofilm effect, reducing biofilm formation by nearly 50% and pre-formed biofilm masses by 25%. On the other hand, compound 23 exhibited the most significant antivirulence effect, reducing pyocyanin synthesis by over 70%. Thus, our study highlights the potential of 1,3,4-oxadiazoles 15 and 23 as promising scaffolds to combat P. aeruginosa. Additionally, interactive QS systems should be considered to achieve maximal anti-QS activity against this clinically relevant species.<\/jats:p>","DOI":"10.3390\/molecules28155866","type":"journal-article","created":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T11:23:03Z","timestamp":1691061783000},"page":"5866","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Synthesis and Biological Evaluation of New Quinoline and Anthranilic Acid Derivatives as Potential Quorum Sensing Inhibitors"],"prefix":"10.3390","volume":"28","author":[{"given":"Ivana","family":"Perkovi\u0107","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Poljak","sequence":"additional","affiliation":[{"name":"Selvita Ltd., 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5325-925X","authenticated-orcid":false,"given":"Kirsi","family":"Savijoki","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Faculty of Agriculture and Forestry, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4508-3060","authenticated-orcid":false,"given":"Pekka","family":"Varmanen","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Faculty of Agriculture and Forestry, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0253-4028","authenticated-orcid":false,"given":"Gordana","family":"Maravi\u0107-Vlahovi\u010dek","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Beus","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Ku\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"D\u017eaji\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-1116","authenticated-orcid":false,"given":"Zrinka","family":"Raji\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nrd3013","article-title":"Anti-virulence strategies to combat bacteria-mediated disease","volume":"9","author":"Rasko","year":"2010","journal-title":"Nat. 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