{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:14:25Z","timestamp":1789708465217,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["LP150100752"],"award-info":[{"award-number":["LP150100752"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Quorum sensing (QS) signaling system is important for bacterial growth, adhesion, and biofilm formation resulting in numerous infectious diseases. Dihydropyrrol-2-ones (DHPs) represent a novel class of antimicrobial agents that inhibit QS, and are less prone to develop bacterial resistance due to their non-growth inhibition mechanism of action which does not cause survival pressure on bacteria. DHPs can prevent bacterial colonization and quorum sensing when covalently bound to substrates. In this study, the role of orientation of DHP compounds was investigated after covalent attachment by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)\/N-hydroxysuccinimide (NHS) coupling reaction to amine-functionalized glass surfaces via various positions of the DHP scaffold. The functionalized glass surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and contact angle measurements and tested for their in vitro biological activity against S. aureus and P. aeruginosa. DHPs attached via the N-1 position resulted in the highest antibacterial activities against S. aureus, while no difference was observed for DHPs attached either via the N-1 position or the C-4 phenyl ring against P. aeruginosa.<\/jats:p>","DOI":"10.3390\/molecules24142676","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T10:44:51Z","timestamp":1563878691000},"page":"2676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Role of Orientation of Surface Bound Dihydropyrrol-2-ones (DHP) on Biological Activity"],"prefix":"10.3390","volume":"24","author":[{"given":"Aditi","family":"Taunk","sequence":"first","affiliation":[{"name":"School of Chemistry, University of New South Wales, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0828-9980","authenticated-orcid":false,"given":"Renxun","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Iskander","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitty K. K.","family":"Ho","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basmah","family":"Almohaywi","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David StClair","family":"Black","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D. P.","family":"Willcox","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Science, University of New South Wales, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naresh","family":"Kumar","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,23]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2000). The World Health Report 2000\u2013Health Systems: Improving Performance, World Health Organization."},{"key":"ref_2","unstructured":"Gatermann, S., Funfstuck, R., Handrick, W., Leitritz, L., Naber, K., Podbielski, A., Schmidt, H., Sester, U., Straube, E., and Wittke, J.W. (2005). MIQ 02: Urinary Tract Infections: Quality Standards for Microbiological Infections, Urban & Fischer."},{"key":"ref_3","unstructured":"US Centers for Disease Control and Prevention (2013). Antibiotic Resistance Threats in the United States."},{"key":"ref_4","unstructured":"O\u2019Neill, J. (2019, June 20). Tackling Drug-Resistant Infections Globally: Final Report and Recommendations. Available online: https:\/\/amr-review.org\/sites\/default\/files\/160525_Final%20paper_with%20cover.pdf."},{"key":"ref_5","unstructured":"O\u2019Neill, J. (2019, June 20). Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. Available online: https:\/\/amr-review.org\/sites\/default\/files\/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1056\/NEJMcp1107675","article-title":"Infections of Cardiovascular Implantable Electronic Devices","volume":"367","author":"Baddour","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jhin.2009.02.010","article-title":"A review of dental implants and infection","volume":"72","author":"Pye","year":"2009","journal-title":"J. Hosp. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"52","DOI":"10.12998\/wjcc.v3.i1.52","article-title":"Implant biomaterials: A comprehensive review","volume":"3","author":"Saini","year":"2015","journal-title":"World J. Clin. Cases"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"176","DOI":"10.4161\/biom.22905","article-title":"Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions","volume":"2","author":"Ribeiro","year":"2012","journal-title":"Biomatter"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1007\/s00405-011-1818-1","article-title":"Postoperative complications in cochlear implants: A retrospective analysis of 438 consecutive cases","volume":"269","author":"Ciorba","year":"2012","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/j.juro.2012.05.080","article-title":"Infections versus penile implants: The war on bugs","volume":"189","author":"Muench","year":"2013","journal-title":"J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"391","DOI":"10.7326\/0003-4819-132-5-200003070-00009","article-title":"Prevention of Instravascular Catheter-Related Infections","volume":"132","author":"Mermel","year":"2000","journal-title":"Ann. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"395","DOI":"10.7326\/0003-4819-133-5-200009050-00026","article-title":"Correction: Catheter-Related Bloodstream Infections","volume":"133","author":"Mermel","year":"2000","journal-title":"Ann. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"163S","DOI":"10.1046\/j.1365-2672.92.5s1.6.x","article-title":"Susceptibility of antibiotic-resistant gram-negative bacteria to biocides: a perspective from the study of catheter biofilms","volume":"92","author":"Stickler","year":"2002","journal-title":"J. Appl. Microbiol. Symp. Suppl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1136\/bjo.82.11.1312","article-title":"Intraocular lens implants and risk of endophthalmitis","volume":"82","author":"Bainbridge","year":"1998","journal-title":"Br. J. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1039\/b515219b","article-title":"Reducing implant-related infections: active release strategies","volume":"35","author":"Hetrick","year":"2006","journal-title":"Chem. Soc. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1146\/annurev.med.59.110106.132000","article-title":"Bacterial and fungal biofilm infections","volume":"59","author":"Lynch","year":"2008","journal-title":"Annu. Rev. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"153rv10","DOI":"10.1126\/scitranslmed.3004528","article-title":"Biomaterial-Associated Infection: Locating the Finish Line in the Race for the Surface","volume":"4","author":"Busscher","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_19","unstructured":"Kumar, N., and Iskander, G. (2013). Furanone Compounds and Lactam Analogues Thereof. (No. 8,586,618), U.S. Patent."},{"key":"ref_20","unstructured":"Kumar, N., and Iskander, G. (2014). Novel Lactams 2007. (2007\/085042 A1), WO."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1128\/AAC.05814-11","article-title":"Immobilization of antibacterial dihydropyrrol-2-ones on functional polymer supports to prevent bacterial infections in vivo","volume":"56","author":"Ho","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1016\/j.biomaterials.2013.11.072","article-title":"Quorum sensing inhibitory activities of surface immobilized antibacterial dihydropyrrolones via click chemistry","volume":"35","author":"Ho","year":"2014","journal-title":"Biomaterials"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1021\/acsbiomaterials.6b00579","article-title":"Poly(ethylene glycol)-Based Coatings Combining Low-Biofouling and Quorum-Sensing Inhibiting Properties to Reduce Bacterial Colonization","volume":"3","author":"Ozcelik","year":"2016","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1000238","DOI":"10.4172\/2155-952X.1000238","article-title":"Surface immobilization of antibacterial quorum sensing inhibitors by photochemical activation","volume":"6","author":"Taunk","year":"2016","journal-title":"J. Biotechnol. Biomater."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.bmcl.2019.03.004","article-title":"Dihydropyrrolones as bacterial quorum sensing inhibitors","volume":"29","author":"Almohaywi","year":"2019","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1080\/08927014.2010.531463","article-title":"Characterisation and in vitro activities of surface attached dihydropyrrol-2-ones against Gram-negative and Gram-positive bacteria","volume":"26","author":"Ho","year":"2010","journal-title":"Biofouling"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9733","DOI":"10.1021\/am502170s","article-title":"Surface modification by allylamine plasma polymerization promotes osteogenic differentiation of human adipose-derived stem cells","volume":"6","author":"Liu","year":"2014","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1039\/b707326g","article-title":"Effect of chitosan membrane surface modification via plasma induced polymerization on the adhesion of osteoblast-like cells","volume":"17","author":"Marques","year":"2007","journal-title":"J. Mater. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S108","DOI":"10.1086\/321834","article-title":"Development and spread of bacterial resistance to antimicrobial agents: an overview","volume":"33","author":"Tenover","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_30","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":"Clatworthy","year":"2007","journal-title":"Nat. Chem. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1099\/00221287-148-1-87","article-title":"Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound","volume":"148","author":"Hentzer","year":"2002","journal-title":"Microbiology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1021\/jm200825u","article-title":"Ethionamide boosters. 2. Combining bioisosteric replacement and structure-based drug design to solve pharmacokinetic issues in a series of potent 1,2,4-oxadiazole EthR inhibitors","volume":"55","author":"Flipo","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1146\/annurev.biochem.67.1.509","article-title":"The green fluorescent protein","volume":"67","author":"Tsien","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"ref_34","first-page":"9","article-title":"Green fuorescent protein\u2014A bright idea for the study of bacterial protein localization","volume":"204","author":"Phillips","year":"2001","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.1093\/emboj\/cdg366","article-title":"Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors","volume":"22","author":"Hentzer","year":"2003","journal-title":"EMBO J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12281","DOI":"10.1073\/pnas.1005485107","article-title":"Membrane potential is important for bacterial cell division","volume":"107","author":"Strahl","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1128\/IAI.74.2.910-919.2006","article-title":"N-acylhomoserine lactones antagonize virulence gene expression and quorum sensing in Staphylococcus aureus","volume":"74","author":"Qazi","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"881","DOI":"10.3201\/eid0809.020063","article-title":"Biofilms: Microbial life on surfaces","volume":"8","author":"Donlan","year":"2002","journal-title":"Emerg. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3217","DOI":"10.1016\/S0142-9612(01)00159-4","article-title":"Bactetial adhesion to surface hydrophlic and hydrophobic contact lenses","volume":"22","author":"Bruinsma","year":"2001","journal-title":"Biomaterials"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1177\/0022034515587690","article-title":"Effects of material properties on bacterial adhesion and biofilm formation","volume":"94","author":"Song","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1002\/jbm.a.35277","article-title":"Escherichia coli adhesion, biofilm development and antibiotic susceptibility on biomedical materials","volume":"103","author":"Gomes","year":"2015","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7563","DOI":"10.1021\/es400901u","article-title":"Effects of surface charge and hydrophobicity on anodic biofilm formation, community composition, and current generation in bioelectrochemical systems","volume":"47","author":"Guo","year":"2013","journal-title":"Environ. Sci. Technol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3973","DOI":"10.1128\/aem.59.11.3973-3977.1993","article-title":"Physicochemical cell-surface and adhesive properties of coryneform bacteria related to the presence and chain-length of mycolic acids","volume":"59","author":"Bendinger","year":"1993","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/(SICI)1097-4636(199823)43:3<338::AID-JBM16>3.0.CO;2-B","article-title":"Concise review of mechanisms of bacterial adhesion to biomaterial surfaces","volume":"43","author":"An","year":"1998","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4371","DOI":"10.1016\/j.actbio.2012.07.029","article-title":"Characterization of chemoselective surface attachment of the cationic peptide melimine and its effects on antimicrobial activity","volume":"8","author":"Chen","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4174","DOI":"10.1021\/acsbiomaterials.8b00816","article-title":"Dual-Action Biomaterial Surfaces with Quorum Sensing Inhibitor and Nitric Oxide to Reduce Bacterial Colonization","volume":"4","author":"Taunk","year":"2018","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9320","DOI":"10.1021\/la701035g","article-title":"Functionalization of acetylene-terminated monolayers on Si(100) surfaces: A click chemistry approach","volume":"23","author":"Ciampi","year":"2007","journal-title":"Langmuir"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1099\/mic.0.2007\/009092-0","article-title":"Biofilm differentiation and dispersal in mucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis","volume":"153","author":"Kirov","year":"2007","journal-title":"Microbiology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7344","DOI":"10.1128\/JB.00779-06","article-title":"Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa","volume":"188","author":"Barraud","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_50","first-page":"36","article-title":"Image processing with imageJ","volume":"11","author":"Ram","year":"2004","journal-title":"Biophotonics Int."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/14\/2676\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:08:49Z","timestamp":1760188129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/14\/2676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,23]]},"references-count":50,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["molecules24142676"],"URL":"https:\/\/doi.org\/10.3390\/molecules24142676","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,23]]}}}