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Quorum sensing (QS) regulates various cellular processes that are important for the establishment and survival of microbial communities on the host. However, QS inhibitors for the treatment of P. aeruginosa biofilms remain under-researched, partly due to the complexity of QS signalling pathways and the challenge of developing non-toxic inhibitors. Herein, the bioactivity of 2-{(2E)-2-[1-(pyridin-2-yl)ethylidene]hydrazinyl}-1,3-thiazole-4-carboxylic acid (TTNF37), a novel pyridine-based thiazolyl-hydrazone (PTH), was investigated. The compound antimicrobial activity was evaluated against a broad spectrum of microorganisms, its antioxidant potential was assessed using different assays, and its QS-inhibitory effect on P. aeruginosa was studied using bioreporter strains. The effect on P. aeruginosa biofilm formation was analysed in terms of biomass, culturability, and metabolic activity, structure, and cell membrane integrity, while virulence factors were evaluated through absorbance measurements. In addition, molecular docking studies were performed to predict the drug\u2019s interactions with essential QS proteins and biological targets. TTNF37 exhibited potent antimicrobial activity with low to moderate minimum inhibitory concentrations against clinically relevant Gram-negative and Gram-positive bacteria, as well as fungi and yeasts. It also showed antioxidant activity, with variable effectiveness across different radicals and systems. TTNF37 inhibited the 3-oxo-C12-HSL-dependent QS system of P. aeruginosa in a dose-dependent manner, with reductions ranging from 26% to 98%. It also impaired the production and detection of 3-oxo-C12-HSL, resulting in a 56% and 65% decrease in bioluminescence, respectively. Molecular docking studies revealed strong binding interactions with LasI and LasR proteins, with affinity values exceeding those of furvina, a known potent QS inhibitor. Molecular dynamics simulations validated stable TTNF37 binding to LasR and LasI. Both experimental and docking data indicate a significant interaction with human serum albumin (HSA). TTNF37 also significantly reduced pyocyanin production and prevented biofilm set-up with a reduction of 50% in biomass with pronounced alterations in biofilm structure. These results indicate the potential of TTNF37 and related PTHs for treating biofilm-associated infections.<\/jats:p>","DOI":"10.3390\/ijms27041784","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:28:11Z","timestamp":1770910091000},"page":"1784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Pyridine-Based Thiazolyl-Hydrazone as a Promising Attenuator of Pseudomonas aeruginosa Pathogenicity by Targeting Quorum Sensing"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6929-6805","authenticated-orcid":false,"given":"Anabela","family":"Borges","sequence":"first","affiliation":[{"name":"LEPABE (Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering), ALiCE (Associate Laboratory for Innovation in Chemical Engineering), Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"},{"name":"DEQB\u2014Department of Chemical and Biological Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s\/n, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6817-7409","authenticated-orcid":false,"given":"Sanja","family":"Kokanov","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia"}]},{"given":"Miguel M.","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"LEPABE (Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering), ALiCE (Associate Laboratory for Innovation in Chemical Engineering), Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"},{"name":"MedInUP, Center for Drug Discovery and Innovative Medicines, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7489-6132","authenticated-orcid":false,"given":"Predrag","family":"Risti\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia"}]},{"given":"Irena","family":"Novakovi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Njego\u0161eva 12, 11000 Belgrade, Serbia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5086-9017","authenticated-orcid":false,"given":"Vladimir","family":"Dobri\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0932-889X","authenticated-orcid":false,"given":"Milan","family":"Nikoli\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4848-2737","authenticated-orcid":false,"given":"Mire","family":"Zloh","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, 29\/39 Brunswick Square, London WC1N 1AX, UK"},{"name":"Faculty of Pharmacy Novi Sad, University Business Academy in Novi Sad, Heroja Pinkija 4, 21101 Novi Sad, Serbia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-3639","authenticated-orcid":false,"given":"Tamara R.","family":"Todorovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3355-4398","authenticated-orcid":false,"given":"Manuel","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"LEPABE (Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering), ALiCE (Associate Laboratory for Innovation in Chemical Engineering), Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"},{"name":"DEQB\u2014Department of Chemical and Biological Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s\/n, 4200-465 Porto, Portugal"}]},{"given":"Nenad R.","family":"Filipovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, University of Belgrade, Nemanjina 6, 11000 Belgrade, Serbia"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.micpath.2018.05.046","article-title":"Developments in Strategies for Quorum Sensing Virulence Factor Inhibition to Combat Bacterial Drug Resistance","volume":"121","author":"Haque","year":"2018","journal-title":"Microb. 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