{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T14:40:00Z","timestamp":1771512000434,"version":"3.50.1"},"reference-count":94,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008809","name":"University of Hail","doi-asserted-by":"publisher","award":["IFP-22 103"],"award-info":[{"award-number":["IFP-22 103"]}],"id":[{"id":"10.13039\/501100008809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Pseudomonas aeruginosa (P. aeruginosa)<\/jats:italic>, a very resilient pathogen, demonstrates a diverse array of virulence factors, the expression of which is closely linked to the quorum sensing(QS) mechanism, which facilitates cell-cell interaction. Quorum sensing (QS) inhibition is a promising strategy for combating bacterial infections. LasR, a transcriptional factor that controls the mechanism of QS in <jats:italic>P. aeruginosa<\/jats:italic>, is a promising target for therapeutic development, because a lot of research has been done on its structure. It has already been established that thiazoles and their compounds have anti-QS potential against P aeruginosa. The study aims to identify new LasR quorum sensing inhibitors (QSIs) derived from novel thiazoles utilizing a structure-based virtual screening technique using the ZINC database. A complete set of 800 molecules (a novel thiazole derivative library) were docked inside the active region of the LasR receptor before being screened using pharmacokinetic and toxicology studies. Among the derivatives that were examined, compounds D_152, D_153, and L_331 were selected as potential inhibitors of LasR in <jats:italic>P. aeruginosa<\/jats:italic> and further studied to obtain a crucial understanding of the binding interactions that take place between inhibitor ligands and LasR. The findings indicated that the pharmacophoric characteristics of the derivative D_152 were comparable to those of the reference thiazole molecule (TC). Moreover, the molecular docking investigations showed that derivative D_152 and reference compound TC both fit the LasR protein\u2019s active area well. Furthermore, TC and D_152\u2019s amino acid interaction graphs with LasR and CviR are nearly identical. Furthermore, compound D_152\u2019s ability to engage with the LasR binding site through the dissolution of the protein\u2019s dimer was demonstrated by molecular dynamics modeling tests conducted over a 50 ns time span, demonstrating its function as a LasR antagonist. Additionally, Density Functional Theory (DFT) study was conducted on compound D_152 in order to determine the electron density of a molecule. According to the research findings, the recently produced thiazole derivative (D_152) has the potential to be used as a QSI against the LasR receptor, which would speed up the fight against the pathogenicity of <jats:italic>P. aeruginosa<\/jats:italic> that is resistant to multiple drugs.<\/jats:p>","DOI":"10.1371\/journal.pone.0320841","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T17:32:02Z","timestamp":1745343122000},"page":"e0320841","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular simulation-based investigation of thiazole derivatives as potential LasR inhibitors of Pseudomonas 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Chem"},{"issue":"14","key":"pone.0320841.ref003","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1016\/S1286-4579(00)01327-7","article-title":"The role of quorum sensing in the in vivo virulence of Pseudomonas aeruginosa","volume":"2","author":"KP Rumbaugh","year":"2000","journal-title":"Microbes Infect"},{"issue":"10","key":"pone.0320841.ref004","first-page":"881","article-title":"Quorum sensing and microbial drug resistance","volume":"38","author":"C Yufan","year":"2016","journal-title":"Yi Chuan"},{"issue":"3","key":"pone.0320841.ref005","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jiph.2009.08.003","article-title":"Urinary tract infections caused by Pseudomonas aeruginosa: A minireview","volume":"2","author":"R Mittal","year":"2009","journal-title":"J Infect Public Health"},{"issue":"6","key":"pone.0320841.ref006","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1111\/j.1365-2958.1996.tb02640.x","article-title":"Localization of OccR-activated and TraR-activated promoters that express two ABC-type permeases and the traR gene of Ti plasmid pTiR10","volume":"20","author":"C Fuqua","year":"1996","journal-title":"Mol Microbiol"},{"issue":"2","key":"pone.0320841.ref007","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1128\/CMR.15.2.167-193.2002","article-title":"Biofilms: Survival mechanisms of clinically relevant microorganisms","volume":"15","author":"RM Donlan","year":"2002","journal-title":"Clin Microbiol Rev"},{"issue":"13","key":"pone.0320841.ref008","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.micinf.2003.08.009","article-title":"Antimicrobial resistance of Pseudomonas aeruginosa biofilms","volume":"5","author":"E Drenkard","year":"2003","journal-title":"Microbes Infect"},{"issue":"16","key":"pone.0320841.ref009","doi-asserted-by":"crossref","first-page":"8789","DOI":"10.1073\/pnas.97.16.8789","article-title":"Acyl-homoserine lactone quorum sensing in gram-negative bacteria: A signaling mechanism involved in associations with higher organisms","volume":"97","author":"MR Parsek","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"17","key":"pone.0320841.ref010","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1093\/emboj\/cdf459","article-title":"The crystal structure of the quorum sensing protein TraR bound to its autoinducer and target DNA","volume":"21","author":"A Vannini","year":"2002","journal-title":"EMBO J"},{"key":"pone.0320841.ref011","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/978-3-031-08491-1_4","article-title":"Pseudomonas aeruginosa quorum sensing","author":"SW Miranda","year":"2022","journal-title":"Adv Exp Med Biol"},{"issue":"3","key":"pone.0320841.ref012","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.chembiol.2016.01.006","article-title":"Chemical genetics reveals environment-specific roles for quorum sensing circuits in pseudomonas aeruginosa","volume":"23","author":"MA Welsh","year":"2016","journal-title":"Cell Chem Biol"},{"issue":"14","key":"pone.0320841.ref013","doi-asserted-by":"crossref","first-page":"6424","DOI":"10.1073\/pnas.92.14.6424","article-title":"Autoinducer-mediated regulation of rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa","volume":"92","author":"UA Ochsner","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"20","key":"pone.0320841.ref014","doi-asserted-by":"crossref","first-page":"9427","DOI":"10.1073\/pnas.92.20.9427","article-title":"Multiple N-acyl-L-homoserine lactone signal molecules regulate production of virulence determinants and secondary metabolites in Pseudomonas aeruginosa","volume":"92","author":"MK Winson","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pone.0320841.ref015","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1006\/mpat.2001.0487","article-title":"Detection of Pseudomonas aeruginosa cell-to-cell signals in lung tissue of cystic fibrosis patients","volume":"32","author":"S Favre-Bont\u00e9","year":"2002","journal-title":"Microb Pathog"},{"issue":"1","key":"pone.0320841.ref016","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1046\/j.1365-2958.2003.03672.x","article-title":"The Pseudomonas aeruginosa quinolone signal molecule overcomes the cell density-dependency of the quorum sensing hierarchy, regulates rhl-dependent genes at the onset of stationary phase and can be produced in the absence of LasR","volume":"50","author":"SP Diggle","year":"2003","journal-title":"Mol Microbiol"},{"issue":"4","key":"pone.0320841.ref017","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1139\/cjm-2013-0667","article-title":"Elastase LasB of Pseudomonas aeruginosa promotes biofilm formation partly through rhamnolipid-mediated regulation","volume":"60","author":"H Yu","year":"2014","journal-title":"Can J 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Microbiol"},{"issue":"13","key":"pone.0320841.ref021","doi-asserted-by":"crossref","first-page":"5929","DOI":"10.1021\/acs.jmedchem.5b01698","article-title":"Novel strategies for the treatment of pseudomonas aeruginosa infections","volume":"59","author":"S Wagner","year":"2016","journal-title":"J Med Chem"},{"issue":"9","key":"pone.0320841.ref022","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nchembio.2007.24","article-title":"Targeting virulence: A new paradigm for antimicrobial therapy","volume":"3","author":"AE Clatworthy","year":"2007","journal-title":"Nat Chem Biol"},{"issue":"1","key":"pone.0320841.ref023","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s00253-008-1406-5","article-title":"Virtual screening for novel quorum sensing inhibitors to eradicate biofilm formation of Pseudomonas aeruginosa","volume":"79","author":"Z Zeng","year":"2008","journal-title":"Appl Microbiol 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anti\u2010inflammatory activity of some new spirotriazolotriazine derivatives","volume":"61","author":"AM El\u2010Saghier","year":"2023","journal-title":"J Heterocycl Chem"},{"issue":"6","key":"pone.0320841.ref027","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1021\/jm00401a007","article-title":"Graphics computer-aided receptor mapping as a predictive tool for drug design: development of potent, selective, and stereospecific ligands for the 5-HT1A receptor","volume":"31","author":"MF Hibert","year":"1988","journal-title":"J Med Chem"},{"key":"pone.0320841.ref028","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1146\/annurev.pa.27.040187.001205","article-title":"Computer-aided drug design","volume":"27","author":"GR Marshall","year":"1987","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"2","key":"pone.0320841.ref029","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/wcms.1240","article-title":"In silico toxicology: Computational methods for the prediction of chemical toxicity","volume":"6","author":"AB Raies","year":"2016","journal-title":"Wiley Interdiscip Rev Comput Mol Sci"},{"issue":"1","key":"pone.0320841.ref030","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1038\/s41598-017-02365-0","article-title":"CarcinoPred-EL: Novel models for predicting the carcinogenicity of chemicals using molecular fingerprints and ensemble learning methods","volume":"7","author":"L Zhang","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0320841.ref031","first-page":"411","article-title":"In silico identification of polyphenolic compounds from the grape fruit as quorum sensing inhibitors","volume":"8","author":"S Singh","year":"2016","journal-title":"J Chem Pharm Res"},{"key":"pone.0320841.ref032","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.micpath.2017.03.026","article-title":"Structure based virtual screening for identification of potential quorum sensing inhibitors against LasR master regulator in Pseudomonas aeruginosa","volume":"107","author":"M Kalia","year":"2017","journal-title":"Microb Pathog"},{"issue":"14","key":"pone.0320841.ref033","first-page":"3892","article-title":"Design, synthesis, DNA binding, and docking studies of Thiazoles and Thiazole\u2010containing Triazoles as antibacterials","volume":"3","author":"R Santosh","year":"2018","journal-title":"Chem Select"},{"issue":"10","key":"pone.0320841.ref034","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.3390\/antibiotics11101337","article-title":"Synthesis and antimicrobial activity of New Heteroaryl(aryl) Thiazole derivatives molecular docking studies","volume":"11","author":"V Kartsev","year":"2022","journal-title":"Antibiotics (Basel)"},{"issue":"46","key":"pone.0320841.ref035","doi-asserted-by":"crossref","first-page":"28581","DOI":"10.1039\/D1RA03882F","article-title":"Emergent antibacterial activity of N-(thiazol-2-yl)benzenesulfonamides in conjunction with cell-penetrating octaarginine","volume":"11","author":"P Ratrey","year":"2021","journal-title":"RSC Adv"},{"key":"pone.0320841.ref036","doi-asserted-by":"crossref","first-page":"116685","DOI":"10.1016\/j.ejmech.2024.116685","article-title":"Discovery and optimization of thiazole-based quorum sensing inhibitors as potent blockers of Pseudomonas aeruginosa pathogenicity","volume":"276","author":"AS Abdelsamie","year":"2024","journal-title":"Eur J Med Chem"},{"issue":"2","key":"pone.0320841.ref037","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1007\/s00044-013-0672-7","article-title":"Synthesis and anti-biofilm activity of thiazole Schiff bases","volume":"23","author":"PG More","year":"2013","journal-title":"Med Chem Res"},{"issue":"97","key":"pone.0320841.ref038","doi-asserted-by":"crossref","first-page":"80027","DOI":"10.1039\/C5RA12925G","article-title":"Design, synthesis and biological evaluation of novel unsymmetrical azines as quorum sensing inhibitors","volume":"5","author":"SS Chourasiya","year":"2015","journal-title":"RSC Adv"},{"key":"pone.0320841.ref039","volume-title":"Cambridge Soft Corporation","author":"Ultra C. 6.0 and Chem3D Ultra","year":"2001"},{"issue":"1","key":"pone.0320841.ref040","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s12551-013-0130-2","article-title":"Receptor-ligand molecular docking","volume":"6","author":"IA Guedes","year":"2014","journal-title":"Biophys Rev"},{"key":"pone.0320841.ref041","doi-asserted-by":"crossref","DOI":"10.26434\/chemrxiv.12108546.v1","article-title":"Battle against coronavirus: Repurposing old friends (Food Borne Polyphenols) for new enemy (COVID-19)","author":"S Bhatia","year":"2020"},{"key":"pone.0320841.ref042","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/newbio233223b0","article-title":"Protein Data Bank","volume":"233","author":"PD Bank","year":"1971","journal-title":"Nature New Biology"},{"issue":"2","key":"pone.0320841.ref043","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":"O Trott","year":"2010","journal-title":"J Comput Chem"},{"issue":"1","key":"pone.0320841.ref044","first-page":"1","article-title":"In silico docking, ADME and toxicity studies of aryl glyoxamide derivatives as anti-virulence agents","volume":"1","author":"S Bhatia","year":"2019","journal-title":"Trends Pharm Nanotechnol"},{"issue":"1","key":"pone.0320841.ref045","doi-asserted-by":"crossref","first-page":"19142","DOI":"10.1038\/s41598-023-46602-1","article-title":"Green synthesis, biological and molecular docking of some novel sulfonamide thiadiazole derivatives as potential insecticidal against Spodoptera littoralis","volume":"13","author":"AM El-Saghier","year":"2023","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0320841.ref046","doi-asserted-by":"crossref","first-page":"147","DOI":"10.4314\/bcse.v38i1.12","article-title":"New iron(III), cobalt(II), nickel(II), copper(II), zinc(II) mixed-ligand complexes: Synthesis, structural, DFT, molecular docking and antimicrobial analysis","volume":"38","author":"HM Abd El-Lateef","year":"2023","journal-title":"Bull Chem Soc Eth"},{"issue":"1","key":"pone.0320841.ref047","article-title":"Antibacterial, antifungal, anti\u2010inflammatory evaluation, molecular docking, and density functional theory exploration of 2\u2010(1H\u2010benzimidazol\u20102\u2010yl)guanidine mixed\u2010ligand complexes: Synthesis and characterization","volume":"38","author":"HM Abd El\u2010Lateef","year":"2023","journal-title":"Appl Organomet Chem"},{"issue":"34","key":"pone.0320841.ref048","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.1016\/S0040-4039(01)94977-9","article-title":"A new model for calculating atomic charges in molecules","volume":"19","author":"J Gasteiger","year":"1978","journal-title":"Tetrahedron Lett"},{"key":"pone.0320841.ref049","doi-asserted-by":"crossref","first-page":"16569","DOI":"10.1038\/srep16569","article-title":"Mechanistic analysis of a synthetic inhibitor of the Pseudomonas aeruginosa LasI quorum-sensing signal synthase","volume":"5","author":"O Lidor","year":"2015","journal-title":"Sci Rep"},{"issue":"11","key":"pone.0320841.ref050","doi-asserted-by":"crossref","first-page":"5629","DOI":"10.1128\/AAC.00955-13","article-title":"Identification of five structurally unrelated quorum-sensing inhibitors of Pseudomonas aeruginosa from a natural-derivative database","volume":"57","author":"SY-Y Tan","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"pone.0320841.ref051","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1128\/AAC.01283-08","article-title":"Computer-aided identification of recognized drugs as Pseudomonas aeruginosa quorum-sensing inhibitors","volume":"53","author":"L Yang","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"pone.0320841.ref052","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"A Daina","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0320841.ref053","first-page":"82","article-title":"Pymol: An open-source molecular graphics tool","volume":"40","author":"WL DeLano","year":"2002","journal-title":"CCP4 Newslett Protein crystallogr"},{"issue":"18","key":"pone.0320841.ref054","doi-asserted-by":"crossref","first-page":"13592","DOI":"10.1074\/jbc.M700556200","article-title":"Molecular insightsinto quorum sensing in the human pathogen Pseudomonas aeruginosa from the structure of the virulence regulator LasR bound to its autoinducer","volume":"282","author":"MJ Bottomley","year":"2007","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0320841.ref055","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1021\/ci049714+","article-title":"ZINC--A free database of commercially available compounds for virtual screening","volume":"45","author":"JJ Irwin","year":"2005","journal-title":"J Chem Inf Model"},{"key":"pone.0320841.ref056","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/B978-0-12-374194-3.00012-3","article-title":"Lead-likeness and drug-likeness","author":"A Polinsky","year":"2008","journal-title":"Pract Med Chem"},{"key":"pone.0320841.ref057","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2012.09.019","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"64","author":"CA Lipinski","year":"2012","journal-title":"Adv Drug Deliv Rev"},{"key":"pone.0320841.ref058","first-page":"418","article-title":"The PreADME approach: Web-based program for rapid prediction of physico-chemical, drug absorption and drug-like properties","author":"SK Lee","year":"2003","journal-title":"EuroQSAR 2002 Des Drugs Crop Protect"},{"key":"pone.0320841.ref059","volume-title":"Maestro desmond interoperability tools, version 3.0","year":"2014"},{"issue":"28","key":"pone.0320841.ref060","doi-asserted-by":"crossref","first-page":"6474","DOI":"10.1021\/jp003919d","article-title":"Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides","volume":"105","author":"GA Kaminski","year":"2001","journal-title":"J Phys Chem B"},{"issue":"6","key":"pone.0320841.ref061","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1080\/00268978500103111","article-title":"Temperature and size dependence for Monte Carlo simulations of TIP4P water","volume":"56","author":"WL Jorgensen","year":"1985","journal-title":"Mol Phys"},{"issue":"12","key":"pone.0320841.ref062","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N\u22c5log(N) method for Ewald sums in large systems","volume":"98","author":"T Darden","year":"1993","journal-title":"J Chem Physics"},{"key":"pone.0320841.ref063","volume-title":"GaussView 5.0","author":"Gaussian 16","year":"2016"},{"key":"pone.0320841.ref064","volume-title":"Gauss view, Version 5","author":"R Dennington","year":"2009"},{"issue":"4","key":"pone.0320841.ref065","doi-asserted-by":"crossref","first-page":"e93414","DOI":"10.1371\/journal.pone.0093414","article-title":"The natural antimicrobial carvacrol inhibits quorum sensing in Chromobacterium violaceum and reduces bacterial biofilm formation at sub-lethal concentrations","volume":"9","author":"SA Burt","year":"2014","journal-title":"PLoS One"},{"issue":"6","key":"pone.0320841.ref066","first-page":"637","article-title":"Inhibition of bacterial quorum sensing by vanilla extract","volume":"42","author":"JH Choo","year":"2006","journal-title":"Lett Appl Microbiol"},{"key":"pone.0320841.ref067","doi-asserted-by":"crossref","first-page":"16158","DOI":"10.1038\/srep16158","article-title":"Tea polyphenols as an antivirulence compound disrupt quorum-sensing regulated pathogenicity of pseudomonas aeruginosa","volume":"5","author":"H Yin","year":"2015","journal-title":"Sci Rep"},{"issue":"6","key":"pone.0320841.ref068","doi-asserted-by":"crossref","first-page":"679","DOI":"10.3390\/antibiotics10060679","article-title":"In silico and in vitro screening of antipathogenic properties of melianthus comosus (Vahl) against Pseudomonas aeruginosa","volume":"10","author":"IT Baloyi","year":"2021","journal-title":"Antibiotics (Basel)"},{"issue":"5","key":"pone.0320841.ref069","doi-asserted-by":"crossref","first-page":"e01997","DOI":"10.1128\/AAC.01997-16","article-title":"Exopolysaccharide-repressing small molecules with antibiofilm and antivirulence activity against Pseudomonas aeruginosa","volume":"61","author":"E van Tilburg Bernardes","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"pone.0320841.ref070","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.molcel.2011.04.003","article-title":"A strategy for antagonizing quorum sensing","volume":"42","author":"G Chen","year":"2011","journal-title":"Mol Cell"},{"issue":"17","key":"pone.0320841.ref071","doi-asserted-by":"crossref","first-page":"4912","DOI":"10.1128\/JB.184.17.4912-4919.2002","article-title":"LasR, a transcriptional activator of Pseudomonas aeruginosa virulence genes, functions as a multimer","volume":"184","author":"P Kiratisin","year":"2002","journal-title":"J Bacteriol"},{"issue":"24","key":"pone.0320841.ref072","doi-asserted-by":"crossref","first-page":"7222","DOI":"10.1128\/JB.185.24.7222-7230.2003","article-title":"Transcription of quorum-sensing system genes in clinical and environmental isolates of Pseudomonas aeruginosa","volume":"185","author":"S Cabrol","year":"2003","journal-title":"J Bacteriol"},{"issue":"3","key":"pone.0320841.ref073","first-page":"352","article-title":"Thiazole derivative based topical nanoemulgel for inhibition of bacterial virulence in surface infections","volume":"25","author":"S Bhardwaj","year":"2022","journal-title":"Iran J Basic Med Sci"},{"issue":"6","key":"pone.0320841.ref074","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.3390\/molecules23061385","article-title":"Cobalt complex with thiazole-based ligand as new pseudomonas aeruginosa quorum quencher, biofilm inhibitor and virulence attenuator","volume":"23","author":"A Borges","year":"2018","journal-title":"Molecules"},{"issue":"9","key":"pone.0320841.ref075","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1007\/s10822-012-9599-1","article-title":"Computational discovery of putative quorum sensing inhibitors against LasR and RhlR receptor proteins of Pseudomonas aeruginosa","volume":"26","author":"A Annapoorani","year":"2012","journal-title":"J Comput Aided Mol Des"},{"issue":"6","key":"pone.0320841.ref076","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1039\/C2OB27155A","article-title":"Synthesis and biological evaluation of triazole-containing N-acyl homoserine lactones as quorum sensing modulators","volume":"11","author":"DM Stacy","year":"2013","journal-title":"Org Biomol Chem"},{"issue":"6","key":"pone.0320841.ref077","first-page":"699","article-title":"Growing emergence of drug-resistant Pseudomonas aeruginosa and attenuation of its virulence using quorum sensing inhibitors: A critical review","volume":"24","author":"S Bhardwaj","year":"2021","journal-title":"Iran J Basic Med Sci"},{"issue":"1","key":"pone.0320841.ref078","doi-asserted-by":"crossref","first-page":"7846","DOI":"10.1038\/s41598-021-86424-7","article-title":"Design, synthesis and docking studies of novel thiazole derivatives incorporating pyridine moiety and assessment as antimicrobial agents","volume":"11","author":"RE Khidre","year":"2021","journal-title":"Sci Rep"},{"key":"pone.0320841.ref079","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.addr.2015.03.011","article-title":"In vitro, in silico and integrated strategies for the estimation of plasma protein binding. A review","volume":"86","author":"G Lambrinidis","year":"2015","journal-title":"Adv Drug Deliv Rev"},{"key":"pone.0320841.ref080","first-page":"9258578","article-title":"Molecular docking and in silico ADMET study reveals Acylguanidine 7a as a potential inhibitor of \u03b2-Secretase","author":"CM Nisha","year":"2016","journal-title":"Adv Bioinformatics"},{"key":"pone.0320841.ref081","first-page":"e00570","article-title":"Molecular docking studies, drug-likeness and in-silico ADMET prediction of some novel \u03b2-Amino alcohol grafted 1,4,5-trisubstituted 1,2,3-triazoles derivatives as elevators of p53 protein levels","volume":"10","author":"Z Ya\u2019u Ibrahim","year":"2020","journal-title":"Sci Afr"},{"key":"pone.0320841.ref082","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1006\/rwgn.2001.1543","article-title":"Ames Test","author":"JG Hengstler","year":"2001","journal-title":"Encyclopedia of Genetics"},{"issue":"6","key":"pone.0320841.ref083","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.neuron.2018.08.011","article-title":"Molecular dynamics simulation for all","volume":"99","author":"SA Hollingsworth","year":"2018","journal-title":"Neuron"},{"issue":"5","key":"pone.0320841.ref084","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1021\/cr040426m","article-title":"Molecular dynamics: Survey of methods for simulating the activity of proteins","volume":"106","author":"SA Adcock","year":"2006","journal-title":"Chem Rev"},{"issue":"3","key":"pone.0320841.ref085","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.jmb.2010.06.040","article-title":"Structural and dynamic determinants of ligand binding and regulation of cyclin-dependent kinase 5 by pathological activator p25 and inhibitory peptide CIP","volume":"401","author":"A Cardone","year":"2010","journal-title":"J Mol Biol"},{"issue":"14","key":"pone.0320841.ref086","doi-asserted-by":"crossref","first-page":"6508","DOI":"10.1039\/C4CP00110A","article-title":"NMR mapping of protein conformational landscapes using coordinated behavior of chemical shifts upon ligand binding","volume":"16","author":"A Cembran","year":"2014","journal-title":"Phys Chem Chem Phys"},{"issue":"1","key":"pone.0320841.ref087","doi-asserted-by":"crossref","first-page":"322","DOI":"10.3390\/e16010322","article-title":"Modeling potential energy surfaces: From First-principle approaches to empirical force fields","volume":"16","author":"P Ballone","year":"2013","journal-title":"Entropy"},{"key":"pone.0320841.ref088","volume-title":"Hydrogen bonds in protein ligand complexes. Protein science encyclopedia","author":"MA Williams","year":"2008"},{"key":"pone.0320841.ref089","doi-asserted-by":"crossref","first-page":"136264","DOI":"10.1016\/j.molstruc.2023.136264","article-title":"Lower rim thiacalixarenes derivatives incorporating multiple coordinating carbonyl groups: Synthesis, characterization, ion-responsive ability and DFT computational analysis","author":"A Abdou","year":"2023","journal-title":"J Mol Struct"},{"key":"pone.0320841.ref090","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/623235","article-title":"Comparative DFT Study of phytochemical constituents of the fruits of cucumis trigonus roxb. and cucumis sativus linn","author":"SB Gopalakrishnan","year":"2014","journal-title":"J Comput Methods Phys"},{"issue":"1","key":"pone.0320841.ref091","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/IRJPAC\/2016\/27066","article-title":"Molecular Structure, HOMO-LUMO, MEP and Fukui function analysis of some TTF-donor substituted molecules using DFT (B3LYP) calculations","volume":"12","author":"A Bendjeddou","year":"2016","journal-title":"IRJPAC"},{"key":"pone.0320841.ref092","doi-asserted-by":"crossref","first-page":"111486","DOI":"10.1016\/j.inoche.2023.111486","article-title":"Fe(III), Ni(II), and Cu(II)-moxifloxacin-tri-substituted imidazole mixed ligand complexes: Synthesis, structural, DFT, biological, and protein-binding analysis","volume":"158","author":"HM Abd El-Lateef","year":"2023","journal-title":"Inorg Chem Commun"},{"issue":"11","key":"pone.0320841.ref093","doi-asserted-by":"crossref","first-page":"e7262","DOI":"10.1002\/aoc.7262","article-title":"Efficiency and development of guanidine chelate catalysts for rapid and green synthesis of 7-amino-4,5-dihydro-tetrazolo[1,5-a]pyrimidine-6-carbonitrile derivatives supported by density functional theory (DFT) studies","volume":"37","author":"MAEAAAE-R El-Remaily","year":"2023","journal-title":"Appl Organomet Chem"},{"issue":"9","key":"pone.0320841.ref094","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.2298\/JSC111227111B","article-title":"Molecular modeling and chemometric study of anticancer derivatives of artemisinin","volume":"76","author":"J Barbosa","year":"2011","journal-title":"J Serb Chem Soc"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0330995","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000}}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0320841","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T19:54:53Z","timestamp":1746734093000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0320841"}},"subtitle":[],"editor":[{"given":"Tung","family":"Truong-Thanh","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,22]]},"references-count":94,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0320841","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,22]]}}}