{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:29:53Z","timestamp":1791545393822,"version":"4.3.4"},"reference-count":59,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Council of Occitanie","award":["Pre-maturation 2020"],"award-info":[{"award-number":["Pre-maturation 2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Biofilm formation is considered a major cause of therapeutic failure because bacteria in biofilms have higher protection against antimicrobials. Thus, biofilm-related infections are extremely challenging to treat and pose major concerns for public health, along with huge economic impacts. Pseudomonas aeruginosa, in particular, is a \u201ccritical priority\u201d pathogen, responsible for severe infections, especially in cystic fibrosis patients because of its capacity to form resistant biofilms. Therefore, new therapeutic approaches are needed to complete the pipeline of molecules offering new targets and modes of action. Biofilm formation is mainly controlled by Quorum Sensing (QS), a communication system based on signaling molecules. In the present study, we employed a molecular docking approach (Autodock Vina) to assess two series of chromones-based compounds as possible ligands for PqsR, a LuxR-type receptor. Most compounds showed good predicted affinities for PqsR, higher than the PQS native ligand. Encouraged by these docking results, we synthesized a library of 34 direct and 25 retro chromone carboxamides using two optimized routes from 2-chromone carboxylic acid as starting material for both series. We evaluated the synthesized carboxamides for their ability to inhibit the biofilm formation of P. aeruginosa in vitro. Overall, results showed several chromone 2-carboxamides of the retro series are potent inhibitors of the formation of P. aeruginosa biofilms (16\/25 compound with % inhibition \u2265 50% at 50 \u03bcM), without cytotoxicity on Vero cells (IC50 &gt; 1.0 mM). The 2,4-dinitro-N-(4-oxo-4H-chromen-2-yl) benzamide (6n) was the most promising antibiofilm compound, with potential for hit to lead optimization.<\/jats:p>","DOI":"10.3390\/ph15040417","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:41:30Z","timestamp":1648590090000},"page":"417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Investigation of Direct and Retro Chromone-2-Carboxamides Based Analogs of Pseudomonas aeruginosa Quorum Sensing Signal as New Anti-Biofilm Agents"],"prefix":"10.3390","volume":"15","author":[{"given":"Jeanne","family":"Trognon","sequence":"first","affiliation":[{"name":"Laboratoire de G\u00e9nie Chimique, Universit\u00e9 de Toulouse, CNRS, INPT, UPS, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Vera","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nie Chimique, Universit\u00e9 de Toulouse, CNRS, INPT, UPS, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4211-2583","authenticated-orcid":false,"given":"Maya","family":"Rima","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nie Chimique, Universit\u00e9 de Toulouse, CNRS, INPT, UPS, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9916-689X","authenticated-orcid":false,"given":"Jean-Luc","family":"Stigliani","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination, Universit\u00e9 de Toulouse, CNRS, INPT, UPS, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Amielet","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nie Chimique, Universit\u00e9 de Toulouse, CNRS, INPT, UPS, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salom\u00e9","family":"El Hage","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nie Chimique, Universit\u00e9 de Toulouse, CNRS, INPT, UPS, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0025-9496","authenticated-orcid":false,"given":"Barbora","family":"Lajoie","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nie Chimique, Universit\u00e9 de Toulouse, CNRS, INPT, UPS, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Roques","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nie Chimique, Universit\u00e9 de Toulouse, CNRS, INPT, UPS, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7217-5879","authenticated-orcid":false,"given":"Fatima","family":"El Garah","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nie Chimique, Universit\u00e9 de Toulouse, CNRS, INPT, UPS, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrmicro2415","article-title":"The biofilm matrix","volume":"8","author":"Flemming","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","first-page":"347","article-title":"Biofilms and biocomplexity","volume":"2","author":"Sauer","year":"2007","journal-title":"Microbe"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1128\/MMBR.00013-14","article-title":"Biofilm-Related Infections: Bridging the Gap between Clinical Management and Fundamental Aspects of Recalcitrance toward Antibiotics","volume":"78","author":"Lebeaux","year":"2014","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00181-19","DOI":"10.1128\/CMR.00181-19","article-title":"Antimicrobial Resistance in ESKAPE Pathogens","volume":"33","author":"Forde","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","unstructured":"WHO (2021, October 25). World Health Organization Report 2017. Available online: http:\/\/www.who.int\/en\/news-room\/detail\/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1002\/anie.201307547","article-title":"Overcoming the Unexpected Functional Inversion of a PqsR Antagonist in Pseudomonas aeruginosa: An In Vivo Potent Antivirulence Agent Targeting pqs Quorum Sensing","volume":"53","author":"Lu","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1128\/AAC.00045-11","article-title":"Quorum Sensing Inhibitors Increase the Susceptibility of Bacterial Biofilms to Antibiotics In Vitro and In Vivo","volume":"55","author":"Brackman","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1128\/AAC.02533-15","article-title":"Impairment of Pseudomonas aeruginosa Biofilm Resistance to Antibiotics by Combining the Drugs with a New Quorum-Sensing Inhibitor","volume":"60","author":"Furiga","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.biotechadv.2012.10.004","article-title":"Quorum sensing inhibitors: An overview","volume":"31","author":"Kalia","year":"2013","journal-title":"Biotechnol. Adv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5226","DOI":"10.1002\/anie.201109258","article-title":"2-Aminobenzimidazole Derivatives Strongly Inhibit and Disperse Pseudomonas aeruginosa Biofilms","volume":"51","author":"Frei","year":"2012","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s13238-014-0100-x","article-title":"The hierarchy quorum sensing network in Pseudomonas aeruginosa","volume":"6","author":"Lee","year":"2015","journal-title":"Protein Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1073\/pnas.0307694100","article-title":"Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication","volume":"101","author":"Milot","year":"2004","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14613","DOI":"10.1073\/pnas.251465298","article-title":"A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism","volume":"98","author":"Cao","year":"2001","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1111\/j.1365-2958.2005.05008.x","article-title":"A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms","volume":"59","author":"Barken","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7941","DOI":"10.1021\/acs.jmedchem.6b01720","article-title":"Chromone as a Privileged Scaffold in Drug Discovery: Recent Advances","volume":"60","author":"Reis","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112503","DOI":"10.1016\/j.ejmech.2020.112503","article-title":"Chromones bearing amino acid residues: Easily accessible and potent inhibitors of the breast cancer resistance protein ABCG2","volume":"202","author":"Roussel","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.bmc.2015.01.042","article-title":"Design, synthesis and evaluation of chromone-2-carboxamido-alkylbenzylamines as multifunctional agents for the treatment of Alzheimer\u2019s disease","volume":"23","author":"Liu","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1016\/j.ejmech.2011.02.025","article-title":"Synthesis of chromone carboxamide derivatives with antioxidative and calpain inhibitory properties","volume":"46","author":"Kim","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4960","DOI":"10.1021\/cr400265z","article-title":"Chromone: A valid scaffold in medicinal chemistry","volume":"114","author":"Gaspar","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.ejmech.2014.03.047","article-title":"Chromones as a privileged scaffold in drug discovery: A review","volume":"78","author":"Keri","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4571","DOI":"10.1016\/j.bmcl.2017.08.053","article-title":"Design, synthesis, and SAR study of 3-(benzo[d][1,3]dioxol-5-yl)-N-benzylpropanamide as novel potent synergists against fluconazole-resistant Candida albicans","volume":"27","author":"Cai","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zitko, J., Mindlov\u00e1, A., Val\u00e1\u0161ek, O., Jand\u2019ourek, O., Paterov\u00e1, P., Janou\u0161ek, J., Kone\u010dn\u00e1, K., and Dole\u017eal, M. (2018). Design, Synthesis and Evaluation of N-pyrazinylbenzamides as Potential Antimycobacterial Agents. Molecules, 23.","DOI":"10.3390\/molecules23092390"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1139\/W10-013","article-title":"Growth inhibition of adherent Pseudomonas aeruginosa by an N-butanoyl-l-homoserine lactone analog","volume":"56","author":"Khalilzadeh","year":"2010","journal-title":"Can. J. Microbiol."},{"key":"ref_24","unstructured":"Huey, R., Morris, G.M., and Forli, S. (2012). Using AutoDock 4 and AutoDock Vina with AutoDockTools: A Tutorial, The Scripps Research Institute."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ilangovan, A., Fletcher, M., Rampioni, G., Pustelny, C., Rumbaugh, K., Heeb, S., C\u00e1mara, M., Truman, A., Chhabra, S.R., and Emsley, J. (2013). Structural Basis for Native Agonist and Synthetic Inhibitor Recognition by the Pseudomonas aeruginosa Quorum Sensing Regulator PqsR (MvfR). PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003508"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcimb.2018.00230","article-title":"The Pseudomonas Quinolone Signal (PQS): Not Just for Quorum Sensing Anymore","volume":"8","author":"Lin","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e02158","DOI":"10.1128\/mBio.02158-17","article-title":"Molecular Insights into Function and Competitive Inhibition of Pseudomonas aeruginosa Multiple Virulence Factor Regulator","volume":"9","author":"Kitao","year":"2018","journal-title":"mBio"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.3389\/fmicb.2019.02355","article-title":"In silico Selection and Experimental Validation of FDA-Approved Drugs as Anti-quorum Sensing Agents","volume":"10","author":"Mellini","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Soukarieh, F., Vico Oton, E., Dubern, J.-F., Gomes, J., Halliday, N., De Pilar Crespo, M., Ram\u00edrez-Prada, J., Insuasty, B., Abonia, R., and Quiroga, J. (2018). In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa. Molecules, 23.","DOI":"10.3390\/molecules23020257"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1021\/acsinfecdis.1c00175","article-title":"Design and Evaluation of New Quinazolin-4(3H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa","volume":"7","author":"Soukarieh","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1007\/s00044-016-1691-y","article-title":"Synthesis and evaluation of chromone-2-carboxamide derivatives as cytotoxic agents and 5-lipoxygenase inhibitors","volume":"25","author":"Lajoie","year":"2016","journal-title":"Med. Chem. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6446","DOI":"10.1016\/j.tetlet.2011.09.095","article-title":"Accelerating lead optimization of chromone carboxamide scaffold throughout microwave-assisted organic synthesis","volume":"52","author":"Cagide","year":"2011","journal-title":"Tetrahedron Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bcp.2012.03.007","article-title":"Discovery of novel A3 adenosine receptor ligands based on chromone scaffold","volume":"84","author":"Gaspar","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"46972","DOI":"10.1039\/C6RA02347A","article-title":"Discovery of the first A1 adenosine receptor ligand based on the chromone scaffold","volume":"6","author":"Cagide","year":"2016","journal-title":"RSC Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5879","DOI":"10.1021\/acs.jmedchem.6b00527","article-title":"Discovery of New Chemical Entities for Old Targets: Insights on the Lead Optimization of Chromone-Based Monoamine Oxidase B (MAO-B) Inhibitors","volume":"59","author":"Reis","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1021\/ol9026232","article-title":"N-Heterocyclic Carbene-Catalyzed Intramolecular Aldehyde\u2212Nitrile Cross Coupling: An Easy Access to 3- Aminochromones","volume":"12","author":"Vedachalam","year":"2010","journal-title":"Org. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13509","DOI":"10.1039\/C9NJ02650A","article-title":"NHC-catalyzed green synthesis of functionalized chromones: DFT mechanistic insights and in vitro activities in cancer cells","volume":"43","author":"Murugesh","year":"2019","journal-title":"New J. Chem."},{"key":"ref_39","first-page":"13","article-title":"Synthesis and pharmacological properties of new compounds related to 2-aminochromone","volume":"11","author":"Payard","year":"1976","journal-title":"Eur. J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1055\/s-2005-869965","article-title":"Synthesis of 2,2\u2032-Diaminobischromones Using a Modified Procedure for the Rearrangement of 5-(2-Hydroxyphenyl)isoxazole to 2-Aminochromone","volume":"2005","author":"Ghosh","year":"2005","journal-title":"Synthesis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.bioorg.2018.11.029","article-title":"Synthesis and biological evaluation of 7-(aminoalkyl)pyrazolo[1,5-a]pyrimidine derivatives as cathepsin K inhibitors","volume":"84","author":"Petek","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1080\/17518253.2012.710650","article-title":"Aluminum-catalyzed efficient synthesis of anilides by the acylation of aryl amines under ultrasonic conditions","volume":"6","author":"Reddy","year":"2013","journal-title":"Green Chem. Lett. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Saito, S. (2004). Aluminum in Organic Synthesis. Main Group Metals in Organic Synthesis, Wiley.","DOI":"10.1002\/3527602607.ch6"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7884","DOI":"10.1039\/D0OB01689F","article-title":"The base-induced regioselective radical arylation of 3-aminochromone with aryl hydrazine","volume":"18","author":"Murugesh","year":"2020","journal-title":"Org. Biomol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1021\/acscatal.7b00245","article-title":"A Cross-Coupling Approach to Amide Bond Formation from Esters","volume":"7","author":"Vandavasi","year":"2017","journal-title":"ACS Catal."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10584","DOI":"10.1039\/C7CC06186B","article-title":"Pd\u2013PEPPSI: A general Pd\u2013NHC precatalyst for Buchwald\u2013Hartwig cross-coupling of esters and amides (transamidation) under the same reaction conditions","volume":"53","author":"Shi","year":"2017","journal-title":"Chem. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11323","DOI":"10.1021\/acs.joc.9b01697","article-title":"Direct Conversion of Carboxylic Acids to Various Nitrogen-Containing Compounds in the One-Pot Exploiting Curtius Rearrangement","volume":"84","author":"Kumar","year":"2019","journal-title":"J. Org. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Starkey, M., Lepine, F., Maura, D., Bandyopadhaya, A., Lesic, B., He, J., Kitao, T., Righi, V., Milot, S., and Tzika, A. (2014). Identification of anti-virulence compounds that disrupt quorum-sensing regulated acute and persistent pathogenicity. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004321"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ejmech.2014.04.016","article-title":"Optimization of anti-virulence PqsR antagonists regarding aqueous solubility and biological properties resulting in new insights in structure\u2013activity relationships","volume":"79","author":"Lu","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Rampioni, G., Falcone, M., Heeb, S., Frangipani, E., Fletcher, M.P., Dubern, J.-F., Visca, P., Leoni, L., C\u00e1mara, M., and Williams, P. (2016). Unravelling the Genome-Wide Contributions of Specific 2-Alkyl-4-Quinolones and PqsE to Quorum Sensing in Pseudomonas aeruginosa. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1006029"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"34083","DOI":"10.1038\/srep34083","article-title":"Evidence for Direct Control of Virulence and Defense Gene Circuits by the Pseudomonas aeruginosa Quorum Sensing Regulator, MvfR","volume":"6","author":"Maura","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_52","first-page":"1","article-title":"Quantitative and Qualitative Assessment Methods for Biofilm Growth: A Mini-review","volume":"6","author":"Wilson","year":"2017","journal-title":"Res. Rev. J. Eng. Technol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"13779","DOI":"10.1038\/s41598-021-93115-w","article-title":"Interlaboratory study for the evaluation of three microtiter plate-based biofilm quantification methods","volume":"11","author":"Allkja","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"eaaw1629","DOI":"10.1126\/science.aaw1629","article-title":"Host monitoring of quorum sensing during Pseudomonas aeruginosa infection","volume":"366","author":"Puyskens","year":"2019","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_56","unstructured":"Huey, R., and Morris, G.M. (2005). Using Autodock with AutodockTools: A tutorial, The Scripps Research Institute."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.ejmech.2012.05.033","article-title":"In search for new chemical entities as adenosine receptor ligands: Development of agents based on benzo-\u03b3-pyrone skeleton","volume":"54","author":"Gaspar","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_58","first-page":"2392","article-title":"Nouveau mode de pr\u00e9paration du chlorure d\u2019acide chromone carboxylique-2","volume":"7\u20138","author":"Payard","year":"1973","journal-title":"Bull. Soc. Chim. Fr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1128\/AAC.46.5.1469-1474.2002","article-title":"Interactions between biocide cationic agents and bacterial biofilms","volume":"46","author":"Campanac","year":"2002","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/4\/417\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:46:07Z","timestamp":1760136367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/4\/417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,29]]},"references-count":59,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ph15040417"],"URL":"https:\/\/doi.org\/10.3390\/ph15040417","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,29]]}}}