Isolation of the New Cytotoxic Polyketide (−)-R-Talaropinophiloic Acid Guided by an Integrated Metabolomics-Dereplication Approach

Isolation of the New Cytotoxic Polyketide (−)-R-Talaropinophiloic Acid Guided by an Integrated Metabolomics-Dereplication Approach | 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 Isolation of the New Cytotoxic Polyketide (−)-R-Talaropinophiloic Acid Guided by an Integrated Metabolomics-Dereplication Approach Marcus Vinicius Marques, Andresa Hiromi Sakai, Lucas Haidar Martorano, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9476499/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract As part of our ongoing bioprospecting program targeting endophytic fungi, the strain J6 was isolated from . Its metabolic potential was evaluated through a combined metabolomics-dereplication workflow based on an in-house high-resolution mass spectrometry (HRMS) database of metabolites. The strategy enabled rapid annotation of known metabolites and guided the isolation of potentially new specialized metabolites. Chromatographic fractionation of the crude extract from J6 cultivated on potato dextrose agar supplemented with ammonium sulphate afforded two polyketides: the new (-)--talaropinophiloic acid () and the known 3--methylfunicone (). Their chemical structures were determined by Nuclear Magnetic Resonance (NMR), Circular Dichroism (CD), and HRMS analyses. The cytotoxic activities were assessed against the muscle-invasive bladder cancer cell line T24 by MTT assay, yielding IC₅₀ values of 204.70 µM for and 59.68 µM for , compared with 6.4 µM for the positive control cisplatin. Assays against the non-tumor RPE-1 cell line showed that displayed a CC₅₀ of 16.62 µM, whereas was non-toxic, highlighting as highly selective for cancer cells. Overall, this work expands knowledge of the chemical diversity of the genus and underscores its potential as a promising source of new bioactive polyketides. Cytotoxicity Endophytic fungi Euphorbia umbellata metabolomics Polyketides Talaromyces pinophilus Full Text Additional Declarations No competing interests reported. Supplementary Files suportinginformation.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 18 May, 2026 Reviewers agreed at journal 17 May, 2026 Reviews received at journal 17 May, 2026 Reviews received at journal 13 May, 2026 Reviewers agreed at journal 13 May, 2026 Reviewers agreed at journal 12 May, 2026 Reviewers agreed at journal 11 May, 2026 Reviews received at journal 30 Apr, 2026 Reviewers agreed at journal 28 Apr, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviewers invited by journal 22 Apr, 2026 Editor assigned by journal 21 Apr, 2026 Submission checks completed at journal 21 Apr, 2026 First submitted to journal 20 Apr, 2026 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. 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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-9476499","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":630826452,"identity":"43e49b2d-8757-41fb-8423-439173176a20","order_by":0,"name":"Marcus Vinicius Marques","email":"","orcid":"","institution":"Universidade Federal da Bahia","correspondingAuthor":false,"prefix":"","firstName":"Marcus","middleName":"Vinicius","lastName":"Marques","suffix":""},{"id":630826453,"identity":"b2070da2-14be-4ebe-8ce8-ad8a11c6744a","order_by":1,"name":"Andresa Hiromi Sakai","email":"","orcid":"","institution":"Universidade Estadual de Londrina","correspondingAuthor":false,"prefix":"","firstName":"Andresa","middleName":"Hiromi","lastName":"Sakai","suffix":""},{"id":630826454,"identity":"63f120f7-7c42-4e13-9c7e-fd892775291e","order_by":2,"name":"Lucas Haidar Martorano","email":"","orcid":"","institution":"Federal Fluminense University – UFF","correspondingAuthor":false,"prefix":"","firstName":"Lucas","middleName":"Haidar","lastName":"Martorano","suffix":""},{"id":630826455,"identity":"f33e5ce4-dd5b-4e2e-b7c2-819744296779","order_by":3,"name":"Viviani N. 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Its metabolic potential was evaluated through a combined metabolomics-dereplication workflow based on an in-house high-resolution mass spectrometry (HRMS) database of metabolites. The strategy enabled rapid annotation of known metabolites and guided the isolation of potentially new specialized metabolites. Chromatographic fractionation of the crude extract from J6 cultivated on potato dextrose agar supplemented with ammonium sulphate afforded two polyketides: the new (-)--talaropinophiloic acid () and the known 3--methylfunicone (). Their chemical structures were determined by Nuclear Magnetic Resonance (NMR), Circular Dichroism (CD), and HRMS analyses. The cytotoxic activities were assessed against the muscle-invasive bladder cancer cell line T24 by MTT assay, yielding IC₅₀ values of 204.70 \u0026micro;M for and 59.68 \u0026micro;M for , compared with 6.4 \u0026micro;M for the positive control cisplatin. Assays against the non-tumor RPE-1 cell line showed that displayed a CC₅₀ of 16.62 \u0026micro;M, whereas was non-toxic, highlighting as highly selective for cancer cells. 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