{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:23:32Z","timestamp":1787840612424,"version":"build-2784847793"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Bacterial biofilms are highly resistant to antibiotics, leading to chronic infections. New approaches targeting biofilm formation (antivirulence) are urgently needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>\n                      To evaluate the antibiofilm efficacy of repurposed small-molecule drugs against\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      , and to investigate their mechanisms of action via\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      assays and in silico modeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Twenty-nine compounds were screened for antibacterial activity (MIC) and for biofilm inhibition using microtiter plate assays. Seven lead compounds were identified and further tested for biofilm prevention and disruption. Computational studies included molecular docking of leads to key targets (e.g.\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      LasR quorum-sensing receptor,\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      sortase A), 100 ns molecular dynamics simulations, and ADMET property prediction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The lead compounds showed potent, dose-dependent inhibition of\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      biofilm formation (approximately 49\u201387% at 250 \u00b5g\/mL, and 71\u2013100% at 500 \u00b5g\/mL) without affecting planktonic growth (MIC &gt;250 \u00b5g\/mL). Two compounds (KAUS-31, KAUS-38) completely prevented\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      biofilm formation at 500 \u00b5g\/mL. Docking suggested high-affinity binding of the leads to LasR (GlideScores up to \u201312.6 vs \u20138.4 for native autoinducer), supporting a quorum-sensing inhibition mechanism. MD simulations indicated the lead\u2013LasR complexes were less stable than the native ligand. All seven compounds showed drug-like profiles (no Lipinski rule violations), high predicted oral absorption, and no serious in silico toxicity flags.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Repurposed small molecules can serve as effective antibiofilm agents against\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      . These compounds likely antagonize bacterial quorum sensing to suppress biofilms, while exhibiting favorable pharmacokinetic properties, highlighting a promising antivirulence strategy against biofilm-associated infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/jpbs.jpbs_1389_25","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T16:00:29Z","timestamp":1761753629000},"page":"140-150","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Experimental and Computational Discovery of Repurposed and Novel Inhibitors Targeting Staphylococcus aureus Biofilms"],"prefix":"10.4103","volume":"17","author":[{"given":"Abdelsattar M.","family":"Omar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"King Fahd Medical Research Center (KFMRC), King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadijah A.","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Almalki","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid O.","family":"Abuelnaga","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrin R. M.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah, Saudi Arabia"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"R1-20260420","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3390\/biologics1030019","article-title":"Pseudomonas aeruginosa biofilm formation and its control","volume":"1","author":"Vetrivel","year":"2021","journal-title":"Biologics"},{"key":"R2-20260420","first-page":"1","article-title":"Biofilms as promoters of bacterial antibiotic resistance and tolerance","volume":"10","author":"Uru\u00e9n","year":"2021","journal-title":"Antibiotics"},{"key":"R3-20260420","doi-asserted-by":"crossref","first-page":"892975","DOI":"10.3389\/fddsv.2022.892975","article-title":"Addressing antibiotic failure\u2014Beyond genetically encoded antimicrobial resistance","volume":"2","author":"Haney","year":"2022","journal-title":"Front Drug Discov"},{"key":"R4-20260420","first-page":"e70629","article-title":"Biofilm formation in chronic infections: A comprehensive review of pathogenesis, clinical implications, and novel therapeutic approaches","volume":"16","author":"Sahoo","year":"2024","journal-title":"Cureus"},{"key":"R5-20260420","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3892\/br.2025.1973","article-title":"Pharmacological strategies for targeting biofilms in otorhinolaryngologic infections and overcoming antimicrobial resistance (Review)","volume":"22","author":"Empitu","year":"2025","journal-title":"Biomed Rep"},{"key":"R6-20260420","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/nrmicro.2017.99","article-title":"Targeting microbial biofilms: Current and prospective therapeutic strategies","volume":"15","author":"Koo","year":"2017","journal-title":"Nat Rev Microbiol"},{"key":"R7-20260420","doi-asserted-by":"crossref","first-page":"e1004152","DOI":"10.1371\/journal.ppat.1004152","article-title":"Broad-spectrum anti-biofilm peptide that targets a cellular stress response","volume":"10","author":"de la Fuente-N\u00fa\u00f1ez","year":"2014","journal-title":"PLoS Pathog"},{"key":"R8-20260420","doi-asserted-by":"crossref","first-page":"124046","DOI":"10.1016\/j.ijpharm.2024.124046","article-title":"Liposomal drug delivery strategies to eradicate bacterial biofilms: Challenges, recent advances, and future perspectives","volume":"655","author":"Panthi","year":"2024","journal-title":"Int J Pharm"},{"key":"R9-20260420","doi-asserted-by":"crossref","first-page":"10243","DOI":"10.3390\/ijms221910243","article-title":"Recent strategies to combat infections from biofilm-forming bacteria on orthopaedic implants","volume":"22","author":"Rodr\u00edguez-Merch\u00e1n","year":"2021","journal-title":"Int J Mol Sci"},{"key":"R10-20260420","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.3390\/genes15091166","article-title":"Molecular targets in streptococcus pyogenes for the development of anti-virulence agents","volume":"15","author":"Cho","year":"2024","journal-title":"Genes (Basel)"},{"key":"R11-20260420","doi-asserted-by":"crossref","first-page":"100827","DOI":"10.1016\/j.mtbio.2023.100827","article-title":"Strategies and materials for the prevention and treatment of biofilms","volume":"23","author":"Kang","year":"2023","journal-title":"Mater Today Bio"},{"key":"R12-20260420","doi-asserted-by":"crossref","first-page":"115389","DOI":"10.1016\/j.ecoenv.2023.115389","article-title":"Bacterial biofilm inhibitors: An overview","volume":"264","author":"Kalia","year":"2023","journal-title":"Ecotoxicol Environ Saf"},{"key":"R13-20260420","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3390\/microorganisms8030425","article-title":"Quorum-sensing regulation of antimicrobial resistance in bacteria","volume":"8","author":"Zhao","year":"2020","journal-title":"Microorganisms"},{"key":"R14-20260420","doi-asserted-by":"crossref","first-page":"109742","DOI":"10.1016\/j.foodres.2020.109742","article-title":"Effects of quorum sensing on the biofilm formation and viable but non-culturable state","volume":"137","author":"Li","year":"2020","journal-title":"Food Res Int"},{"key":"R15-20260420","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.3390\/molecules29071674","article-title":"Research progress on the combination of quorum-sensing inhibitors and antibiotics against bacterial resistance","volume":"29","author":"Wang","year":"2024","journal-title":"Molecules"},{"key":"R16-20260420","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s11030-024-10862-4","article-title":"Quinolone scaffolds as potential drug candidates against infectious microbes: A review","volume":"29","author":"Sharma","year":"2024","journal-title":"Mol Diversity"},{"key":"R17-20260420","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.2174\/1381612821666150310104416","article-title":"Repurposing non-antimicrobial drugs for treatment of staphylococcal infections","volume":"21","author":"Thangamani","year":"2015","journal-title":"Curr Pharm Des"},{"key":"R19-20260420","doi-asserted-by":"crossref","first-page":"5029","DOI":"10.3390\/ijms23095029","article-title":"Giving drugs a second chance: Antibacterial and antibiofilm effects of ciclopirox and ribavirin against cystic fibrosis pseudomonas aeruginosa strains","volume":"23","author":"Di Bonaventura","year":"2022","journal-title":"Int J Mol Sci"},{"key":"R20-20260420","doi-asserted-by":"crossref","first-page":"613","DOI":"10.3390\/antibiotics13070613","article-title":"Unveiling the Antimicrobial, anti-biofilm, and anti-quorum-sensing potential of Paederia foetida Linn. leaf extract against staphylococcus aureus: an integrated in vitro\u2013in silico investigation","volume":"13","author":"Santajit","year":"2024","journal-title":"Antibiotics"},{"key":"R21-20260420","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.3390\/molecules27051484","article-title":"Mechanisms, anti-quorum-sensing actions, and clinical trials of medicinal plant bioactive compounds against bacteria: A comprehensive review","volume":"27","author":"Bouyahya","year":"2022","journal-title":"Molecules"},{"key":"R22-20260420","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3390\/mps7040050","article-title":"In vitro methods for assessing the antibacterial and antibiofilm properties of essential oils as potential root canal irrigants\u2014A simplified description of the technical steps","volume":"7","author":"Diouchi","year":"2024","journal-title":"Methods Protoc"},{"key":"R23-20260420","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s44259-024-00051-6","article-title":"Antibiotic susceptibility testing using minimum inhibitory concentration (MIC) assays","volume":"2","author":"Kade\u0159\u00e1bkov\u00e1","year":"2024","journal-title":"NPJ Antimicrob Resist"},{"key":"R24-20260420","first-page":"e02006","article-title":"Screening the pathogen box for identification of Candida albicans biofilm inhibitors","volume":"61","author":"Vila","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"key":"R25-20260420","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s44371-025-00121-2","article-title":"Disrupting quorum sensing by exploring conformational dynamics and active site flexibility of LasR protein in Pseudomonas aeruginosa","volume":"2","author":"Manu","year":"2025","journal-title":"Discov Chem"},{"key":"R26-20260420","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12866-025-03846-3","article-title":"Characterization of AI-2\/LuxS quorum sensing system in antibiotic resistance, pathogenicity of non carbapenemase-producing carbapenem-resistant Escherichia coli","volume":"25","author":"Xu","year":"2025","journal-title":"BMC Microbiol"},{"key":"R27-20260420","doi-asserted-by":"crossref","first-page":"271917","DOI":"10.3389\/fcimb.2017.00181","article-title":"The ATP-dependent protease ClpP inhibits biofilm formation by regulating Agr and cell wall hydrolase Sle1 in Staphylococcus aureus","volume":"7","author":"Liu","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"R28-20260420","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3390\/molecules28010044","article-title":"Docking and molecular dynamic investigations of phenylspirodrimanes as cannabinoid receptor-2 agonists","volume":"28","author":"Omar","year":"2023","journal-title":"Molecules"},{"key":"R29-20260420","doi-asserted-by":"crossref","first-page":"e38300","DOI":"10.1016\/j.heliyon.2024.e38300","article-title":"Synthesis, characterization, quantum mechanical calculations and biomedical docking studies on curcumin analogs: 2, 6-(Difurfurylidene) cyclohexanone and 2, 6 \u2013 Bis(2,6\u2013Dichloro Benzylidene) Cyclohexanone","volume":"10","author":"Sathiyamoorthi","year":"2024","journal-title":"Heliyon"},{"key":"R30-20260420","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1021\/jm050540c","article-title":"Novel procedure for modeling ligand\/receptor induced fit effects","volume":"49","author":"Sherman","year":"2006","journal-title":"J Med Chem"},{"key":"R31-20260420","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.3390\/ph16091251","article-title":"Molecular dynamics simulations of drug-conjugated cell-penetrating peptides","volume":"16","author":"Iv\u00e1nczi","year":"2023","journal-title":"Pharmaceuticals"},{"key":"R32-20260420","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1007\/s00044-016-1591-1","article-title":"Identification of novel natural compound inhibitors for human complement component 5a receptor by homology modeling and virtual screening","volume":"25","author":"Shaikh","year":"2016","journal-title":"Med Chem Res"},{"key":"R33-20260420","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/nrmicro3232","article-title":"Targeting virulence: Can we make evolution-proof drugs?","volume":"12","author":"Allen","year":"2014","journal-title":"Nat Rev Microbiol"},{"key":"R34-20260420","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1021\/cb5004288","article-title":"Competition studies confirm two major barriers that can preclude the spread of resistance to quorum-sensing inhibitors in bacteria","volume":"9","author":"Gerdt","year":"2014","journal-title":"ACS Chem Biol"}],"container-title":["Journal of Pharmacy and Bioallied Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/jpbs.jpbs_1389_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:25:55Z","timestamp":1787837155000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/jpbs.jpbs_1389_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/jpbs.jpbs_1389_25","relation":{},"ISSN":["0976-4879","0975-7406"],"issn-type":[{"value":"0976-4879","type":"print"},{"value":"0975-7406","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2025-08-06","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}