Synthesized 3-(2-isocyano-6-methylbenzyl)-1H-indole Enhanced Susceptibility of Serratia marcescens to Kanamycinby Occluding Quorum Sensing

Synthesized 3-(2-isocyano-6-methylbenzyl)-1H-indole Enhanced Susceptibility of Serratia marcescens to Kanamycinby Occluding Quorum Sensing | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Synthesized 3-(2-isocyano-6-methylbenzyl)-1H-indole Enhanced Susceptibility of Serratia marcescens to Kanamycinby Occluding Quorum Sensing Jin-Yi Yang, Wei Wang, Shi Tang, Dayong Wang, Chao-yun Cai, Jiang Wang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2794130/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Quorum sensing (QS) inhibition is recognized as a novel drug target for infections caused by drug-resistant pathogens and is an attractive strategy for the development of antipathogenic agents. Herein, we designed and synthesized three parts of3-(2-isocyanobenzyl)-1H-indole derivatives and evaluated their activity as novel quorum sensing inhibitors (QSIs). We found that 3-(2-isocyanobenzyl)-1H-indole derivatives showed promising QS inhibitory activity in the minimum inhibitory concentrations (MICs), biofilm and prodigiosin inhibition assays in Serratia marcescens . In particular, 3-(2-isocyano-6-methylbenzyl)-1H-indole(IMBI, 32 ) was the best candidate by biofilm and prodigiosin inhibition assays screening strategies. Further studies demonstrated, exposureIMBI (1.56 μg/mL, 1/8MICs) to S. marcescens NJ01 significantly inhibited the formation of biofilms by 42%. The IMBI treatment (1.56 μg/mL) on S. marcescens NJ01 notably enhanced the susceptibility of the formed biofilms, destroying the architecture of biofilms up to 40% as evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscope (CLSM). For interference of virulence factors in S. marcescens NJ01, IMBI (3.12 μg/mL, 1/4MICs) inhibited the activity of protease, and extracellular polysaccharides (EPS)by 17% and 51% respectively, which were higher than that of the positive control vanillic acid (VAN). Furthermore, IMBI downregulated the expressions of QS- and biofilm-related genes bsmA , pigP , flhC , rssB , rsmA , and fimC by 0.13-fold to 1.46-fold. To confirm these findings, molecular docking was performed, which indicated that the binding of IMBI to SmaR, RhlI, RhlR, LasR, and CviR could antagonize the expression of QS-linked traits. In addition, molecular dynamic simulations (MD) and energy calculations indicated that the binding of receptors with IMBI was extremely stable. Most importantly, the biofilms of S. marcescens NJ01 were markedly reduced by 50% under IMBI (0.39 μg/mL, 1/32MICs)combining with 0.15 μg/mL kalamycin (KAN). In conclusion, this study highlights the potency of IMBI in inhibiting the virulence factors against S. marcescens. IMBI could be developed as an effective QS inhibitor and anti-biofilm agent to restore or improve drug sensitivity for drug-resistant pathogens. General Microbiology 3-(2-isocyano-6-methylbenzyl)-1H-indole Serratia marcescens quorum sensing biofilm virulence factors kanamycin Full Text Supplementary Files SupplementarydataNC0330.pdf ESI Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2794130","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":190260972,"identity":"bef5e0dd-b4aa-4481-bb33-99dc73af4492","order_by":0,"name":"Jin-Yi Yang","email":"","orcid":"","institution":"Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, 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4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eQuorum sensing (QS) inhibition is recognized as a novel drug target for infections caused by drug-resistant pathogens and is an attractive strategy for the development of antipathogenic agents. Herein, we designed and synthesized three parts of3-(2-isocyanobenzyl)-1H-indole derivatives and evaluated their activity as novel quorum sensing inhibitors (QSIs). We found that 3-(2-isocyanobenzyl)-1H-indole derivatives showed promising QS inhibitory activity in the minimum inhibitory concentrations (MICs), biofilm and prodigiosin inhibition assays in\u003cem\u003e Serratia marcescens\u003c/em\u003e. In particular, 3-(2-isocyano-6-methylbenzyl)-1H-indole(IMBI, \u003cstrong\u003e32\u003c/strong\u003e) was the best candidate by biofilm and prodigiosin inhibition assays screening strategies.\u003cem\u003e \u003c/em\u003eFurther studies demonstrated, exposureIMBI (1.56 μg/mL, 1/8MICs) to \u003cem\u003eS. marcescens \u003c/em\u003eNJ01 significantly inhibited the formation of biofilms by 42%. The IMBI treatment (1.56 μg/mL) on \u003cem\u003eS. marcescens \u003c/em\u003eNJ01 notably enhanced the susceptibility of the formed biofilms, destroying the architecture of biofilms up to 40% as evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscope (CLSM). For interference of virulence factors in \u003cem\u003eS. marcescens \u003c/em\u003eNJ01, IMBI (3.12 μg/mL, 1/4MICs) inhibited the activity of protease, and extracellular polysaccharides (EPS)by 17% and 51% respectively, which were higher than that of the positive control vanillic acid (VAN). Furthermore, IMBI downregulated the expressions of QS- and biofilm-related genes \u003cem\u003ebsmA\u003c/em\u003e,\u003cem\u003epigP\u003c/em\u003e,\u003cem\u003e flhC\u003c/em\u003e, \u003cem\u003erssB\u003c/em\u003e,\u003cem\u003e rsmA\u003c/em\u003e,\u003cem\u003e \u003c/em\u003eand\u003cem\u003e fimC\u003c/em\u003e by 0.13-fold to 1.46-fold. To confirm these findings, molecular docking was performed, which indicated that the binding of IMBI to SmaR, RhlI, RhlR, LasR, and CviR could antagonize the expression of QS-linked traits. In addition, molecular dynamic simulations (MD) and energy calculations indicated that the binding of receptors with IMBI was extremely stable. Most importantly, the biofilms of \u003cem\u003eS. marcescens\u003c/em\u003e NJ01 were markedly reduced by 50% under IMBI (0.39 μg/mL, 1/32MICs)combining with 0.15 μg/mL kalamycin (KAN). In conclusion, this study highlights the potency of IMBI in inhibiting the virulence factors against \u003cem\u003eS. marcescens. \u003c/em\u003eIMBI could be developed as an effective QS inhibitor and anti-biofilm agent to restore or improve drug sensitivity for drug-resistant pathogens.\u003c/p\u003e","manuscriptTitle":"Synthesized 3-(2-isocyano-6-methylbenzyl)-1H-indole Enhanced Susceptibility of Serratia marcescens to Kanamycinby Occluding Quorum Sensing","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-04-10 04:25:44","doi":"10.21203/rs.3.rs-2794130/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c9cc2c1d-218c-4f3b-b3f3-c9ba59ceeb7f","owner":[],"postedDate":"April 10th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":20560758,"name":"General Microbiology"}],"tags":[],"updatedAt":"2023-04-10T04:25:44+00:00","versionOfRecord":[],"versionCreatedAt":"2023-04-10 04:25:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2794130","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2794130","identity":"rs-2794130","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}