Phytochemical Profiling, Network Pharmacology, and Molecular Dynamics Simulations of Sinularia levi Metabolites as Potent α-Glucosidase Inhibitors in Metabolic Syndrome

Phytochemical Profiling, Network Pharmacology, and Molecular Dynamics Simulations of Sinularia levi Metabolites as Potent α-Glucosidase Inhibitors in Metabolic Syndrome | 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 Article Phytochemical Profiling, Network Pharmacology, and Molecular Dynamics Simulations of Sinularia levi Metabolites as Potent α-Glucosidase Inhibitors in Metabolic Syndrome Basma Khalaf Mahmoud, Mamdouh Nabil Samy, Francisco Les, Hesham A. Abou-Zied, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8761838/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 This study has investigated the phytochemical composition and therapeutic potential of the Red Sea soft coral Sinularia levi . Five compounds ( 1–5 ) comprising three glyceryl derivatives, a ceramide, and a diterpene were isolated and characterized. To elucidate their role in metabolic syndrome, an integrated network pharmacology and structure-based modelling workflow was employed. This approach identified 45 shared targets between S. levi metabolites and disease proteins, clustered into inflammatory and metabolic nodes, with α-glucosidase (GAA) emerging as a primary target. Molecular docking against GAA (PDB: 5NN8) identified glyceryl nonacosanol ( 2 ) as the most potent ligand (–8.5 kcal/mol), stabilized by a unique glycerol-head polar clamp involving Glu139 and Lys137. The stability of this complex was confirmed through a 100-ns MD simulation, which demonstrated sustained equilibrium and persistent hydrogen bonding. In vitro assays revealed that the total extract possesses significant antioxidant activity (DPPH IC 50 ​ = 18.66 µg/mL), the isolated compounds exhibited selective enzyme inhibition. In which, Glyceryl nonacosanol ( 2 ) proved to be the most effective α-glucosidase inhibitor (IC 50 ​=326.77 µg/mL), whereas glyceryl pentacosanoate ( 5 ) showed the highest activity against pancreatic lipase (IC 50 ​= 170.75 µg/mL). These findings suggest that S. levi metabolites, particularly glyceryl nonacosanol, represent promising leads for managing postprandial glucose levels. Biological sciences/Biochemistry Biological sciences/Chemical biology Physical sciences/Chemistry Biological sciences/Computational biology and bioinformatics Biological sciences/Drug discovery Sinularia levi network pharmacology antioxidant lipase inhibitor α-glucosidase Full Text Additional Declarations No competing interests reported. Supplementary Files sinulariaSupplementarydata122026.docx 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-8761838","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":588865063,"identity":"20a9a0e9-94c6-4861-a4f9-0ce4c25cb712","order_by":0,"name":"Basma Khalaf Mahmoud","email":"","orcid":"","institution":"Minia University","correspondingAuthor":false,"prefix":"","firstName":"Basma","middleName":"Khalaf","lastName":"Mahmoud","suffix":""},{"id":588865064,"identity":"ab2fd5b8-a7e8-480c-9e90-2cbf5fa2e119","order_by":1,"name":"Mamdouh Nabil Samy","email":"","orcid":"","institution":"Minia University","correspondingAuthor":false,"prefix":"","firstName":"Mamdouh","middleName":"Nabil","lastName":"Samy","suffix":""},{"id":588865065,"identity":"b369f010-ce02-421e-ba57-df7304b029f7","order_by":2,"name":"Francisco Les","email":"","orcid":"","institution":"Universidad San Jorge","correspondingAuthor":false,"prefix":"","firstName":"Francisco","middleName":"","lastName":"Les","suffix":""},{"id":588865066,"identity":"98f419d3-7000-48b2-8701-f6cba1575326","order_by":3,"name":"Hesham A. 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Five compounds (\u003cb\u003e1\u0026ndash;5\u003c/b\u003e) comprising three glyceryl derivatives, a ceramide, and a diterpene were isolated and characterized. To elucidate their role in metabolic syndrome, an integrated network pharmacology and structure-based modelling workflow was employed. This approach identified 45 shared targets between \u003cem\u003eS. levi\u003c/em\u003e metabolites and disease proteins, clustered into inflammatory and metabolic nodes, with α-glucosidase (GAA) emerging as a primary target. Molecular docking against GAA (PDB: 5NN8) identified glyceryl nonacosanol (\u003cb\u003e2\u003c/b\u003e) as the most potent ligand (\u0026ndash;8.5 kcal/mol), stabilized by a unique glycerol-head polar clamp involving Glu139 and Lys137. The stability of this complex was confirmed through a 100-ns MD simulation, which demonstrated sustained equilibrium and persistent hydrogen bonding. \u003cem\u003eIn vitro\u003c/em\u003e assays revealed that the total extract possesses significant antioxidant activity (DPPH IC\u003csub\u003e50\u003c/sub\u003e​ = 18.66 \u0026micro;g/mL), the isolated compounds exhibited selective enzyme inhibition. In which, Glyceryl nonacosanol (\u003cb\u003e2\u003c/b\u003e) proved to be the most effective α-glucosidase inhibitor (IC\u003csub\u003e50\u003c/sub\u003e​=326.77 \u0026micro;g/mL), whereas glyceryl pentacosanoate (\u003cb\u003e5\u003c/b\u003e) showed the highest activity against pancreatic lipase (IC\u003csub\u003e50\u003c/sub\u003e​= 170.75 \u0026micro;g/mL). These findings suggest that \u003cem\u003eS. levi\u003c/em\u003e metabolites, particularly glyceryl nonacosanol, represent promising leads for managing postprandial glucose levels.\u003c/p\u003e","manuscriptTitle":"Phytochemical Profiling, Network Pharmacology, and Molecular Dynamics Simulations of Sinularia levi Metabolites as Potent α-Glucosidase Inhibitors in Metabolic Syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-12 12:00:55","doi":"10.21203/rs.3.rs-8761838/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":"53eed4c0-9625-41df-aadf-53bbeedda92e","owner":[],"postedDate":"February 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":62648386,"name":"Biological sciences/Biochemistry"},{"id":62648387,"name":"Biological sciences/Chemical biology"},{"id":62648388,"name":"Physical sciences/Chemistry"},{"id":62648389,"name":"Biological sciences/Computational biology and bioinformatics"},{"id":62648390,"name":"Biological sciences/Drug discovery"}],"tags":[],"updatedAt":"2026-03-12T04:54:58+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-12 12:00:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8761838","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8761838","identity":"rs-8761838","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}