Synthesis, In vitro Antimicrobial, and In Silico Studies of 2-Hydroxy-1, 2-Diphenylethanone Derivatives

Synthesis, In vitro Antimicrobial, and In Silico Studies of 2-Hydroxy-1, 2-Diphenylethanone Derivatives | 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 Synthesis, In vitro Antimicrobial, and In Silico Studies of 2-Hydroxy-1, 2-Diphenylethanone Derivatives Temesgen Kusse, Daniel Bisrat, Kaleab Asres This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8813407/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 Infectious diseases place a significant impact on the healthcare system. It causes 7.7 million fatalities each year, with a disproportionately high burden in sub-Saharan Africa. Drug resistant pathogens attributed to 4.95 million and 1.27 million are illnesses of bacteria that are resistant to the current medications. Therefore, there is an urgent need for new, safe, and effective compounds to combat antimicrobial resistance. The aim of this study was to synthesize new compounds derived from 2-hydroxy-1,2-diphenylethanone using the Mannich reaction and evaluate their antimicrobial activities against 26 bacterial strains and 4 fungal strains. Three compounds were successfully synthesized and their structures were confirmed as 2-hydroxy-1,2-diphenyl-3-(piperidin-1-yl)propan-1-one ( 2 ), 1-(2-hydroxy-3-oxo-2,3-diphenylpropyl)urea (3), and 3-(diethylamino)-2-hydroxy-1,2-diphenylpropan-1-one (4) using ¹H and ¹³C-NMR spectroscopy. All the synthesized compounds exhibited broad-spectrum antibacterial activity. Compound ( 3) demonstrated the highest activity, with MIC of 10 µg/mL against Shigella sonnei 1, Shigella boydii D13629, and Pseudomonas aeruginosa MDR1 and compound ( 4) demonstrated the highest antifungal activity, with MIC of 200 µg/mL against Candida albicans ATCC 10231, Aspergillus niger ATCC 6275, Penicillium funiculosum NCTC 287, and Penicillium notatum ATCC 11625. Molecular docking showed the compounds interact favorably with conserved residues in the binding site of E. coli DsbA (PDB ID: 8DN0) through hydrogen bonding and hydrophobic interactions, with docking scores of –7.5 kcal/mol compound (3) , –7.1 kcal/mol compound (4) , and –6.5kcal/mol compound (2) . This research suggests verify the molecular docking results experimentally and biological activities, such as antiviral, anticancer, anti-inflammatory, and antioxidant properties and evaluate the safety profile of the produced chemicals, conduct thorough toxicity tests. 2-hydroxy-1 2-diphenylethanone Antimicrobial activity in-silico studies Disulfide bond oxidoreductase (DsbA) Mannich reaction Full Text Additional Declarations No competing interests reported. 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8813407","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":602047246,"identity":"5a852514-b079-46d3-adf8-e738e874bb60","order_by":0,"name":"Temesgen Kusse","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYDADCQYGxgdAmoePkEoeJC3MBiABNlK0sEmAGAS12LN3Jz788csmT3J2j1nl1xw7GTYG5oePbuCzhefsZmPevrRiaZkzZrdltyUDHcZmbJyDT4tE7jZpxp7DifMkcsxuS25jBmrhYZPGq0X+7fafP3v+g7UUS26rJ0KLBO82Bp4fBxJnA7Uwftx2mAgtZ3I3S/M2JCfOnAH0D+O24zxszAT8wt5+duPHH3/sEmfcSN748ee2ant+9uaHj/FpAQPGNhDJYcAMjiVmQsrB4A/YwgeMP4hSPQpGwSgYBSMNAABxWEW4LYD/9gAAAABJRU5ErkJggg==","orcid":"","institution":"Arba Minch University","correspondingAuthor":true,"prefix":"","firstName":"Temesgen","middleName":"","lastName":"Kusse","suffix":""},{"id":602047247,"identity":"6ae3500b-1027-4c9e-ae9c-aaed9119c315","order_by":1,"name":"Daniel Bisrat","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Bisrat","suffix":""},{"id":602047248,"identity":"db3fdcda-65ca-4bf8-bdf8-7dc3c1ba6949","order_by":2,"name":"Kaleab Asres","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Kaleab","middleName":"","lastName":"Asres","suffix":""}],"badges":[],"createdAt":"2026-02-07 07:53:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8813407/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8813407/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109138217,"identity":"82ea1de7-9d10-4b26-8743-bec5a09119f4","added_by":"auto","created_at":"2026-05-13 01:42:36","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":796481,"visible":true,"origin":"","legend":"","description":"","filename":"Temesgenmanuscriptforpuplic2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8813407/v1_covered_dcdabea2-e357-4738-8528-fc2364b08ae8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Synthesis, In vitro Antimicrobial, and In Silico Studies of 2-Hydroxy-1, 2-Diphenylethanone Derivatives","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"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},"keywords":"2-hydroxy-1, 2-diphenylethanone, Antimicrobial activity, in-silico studies, Disulfide bond oxidoreductase (DsbA), Mannich reaction","lastPublishedDoi":"10.21203/rs.3.rs-8813407/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8813407/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eInfectious diseases place a significant impact on the healthcare system. It causes 7.7 million fatalities each year, with a disproportionately high burden in sub-Saharan Africa. Drug resistant pathogens attributed to 4.95 million and 1.27 million are illnesses of bacteria that are resistant to the current medications. Therefore, there is an urgent need for new, safe, and effective compounds to combat antimicrobial resistance. The aim of this study was to synthesize new compounds derived from 2-hydroxy-1,2-diphenylethanone using the Mannich reaction and evaluate their antimicrobial activities against 26 bacterial strains and 4 fungal strains. Three compounds were successfully synthesized and their structures were confirmed as 2-hydroxy-1,2-diphenyl-3-(piperidin-1-yl)propan-1-one (\u003cstrong\u003e2\u003c/strong\u003e), 1-(2-hydroxy-3-oxo-2,3-diphenylpropyl)urea \u003cstrong\u003e(3),\u003c/strong\u003e and 3-(diethylamino)-2-hydroxy-1,2-diphenylpropan-1-one \u003cstrong\u003e(4)\u003c/strong\u003e using ¹H and ¹³C-NMR spectroscopy. All the synthesized compounds exhibited broad-spectrum antibacterial activity. Compound (\u003cstrong\u003e3)\u003c/strong\u003e demonstrated the highest activity, with MIC of 10 µg/mL against \u003cem\u003eShigella sonnei\u003c/em\u003e 1, \u003cem\u003eShigella boydii\u003c/em\u003e D13629, and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e MDR1 and compound (\u003cstrong\u003e4)\u003c/strong\u003e demonstrated the highest antifungal activity, with MIC of 200 µg/mL against \u003cem\u003eCandida albicans\u003c/em\u003e ATCC 10231, \u003cem\u003eAspergillus niger \u003c/em\u003eATCC 6275, \u003cem\u003ePenicillium funiculosum\u003c/em\u003e NCTC 287, and \u003cem\u003ePenicillium notatum\u003c/em\u003eATCC 11625. Molecular docking showed the compounds interact favorably with conserved residues in the binding site of \u003cem\u003eE. coli\u003c/em\u003e DsbA (PDB ID: 8DN0) through hydrogen bonding and hydrophobic interactions, with docking scores of –7.5 kcal/mol compound\u003cstrong\u003e (3)\u003c/strong\u003e, –7.1 kcal/mol compound \u003cstrong\u003e(4)\u003c/strong\u003e, and –6.5kcal/mol compound \u003cstrong\u003e(2)\u003c/strong\u003e. This research suggests verify the molecular docking results experimentally and biological activities, such as antiviral, anticancer, anti-inflammatory, and antioxidant properties and evaluate the safety profile of the produced chemicals, conduct thorough toxicity tests.\u003c/p\u003e","manuscriptTitle":"Synthesis, In vitro Antimicrobial, and In Silico Studies of 2-Hydroxy-1, 2-Diphenylethanone Derivatives","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-09 17:25:33","doi":"10.21203/rs.3.rs-8813407/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":"86477478-0b64-40e3-aca5-a82392c9d280","owner":[],"postedDate":"March 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T01:42:23+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-09 17:25:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8813407","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8813407","identity":"rs-8813407","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}