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Drugs","Marine Drugs"],"abstract":"<jats:p>Antarctic marine-derived fungi represent an underexplored reservoir of bioactive secondary metabolites shaped by extreme environmental pressures. In this study, nine fungal isolates obtained from Antarctic macroalgae, lichens, sponge tissue, and sediments were evaluated for their antimicrobial, anticancer, antibiofilm, and metabolomic profiles. Untargeted LC\u2013MS\/MS molecular networking (GNPS) revealed a chemically rich metabolome, dominated by alkaloids, followed by polyketides, meroterpenoids, and diketopiperazines, with Penicillium crustosum (A15A) emerging as a major biosynthetic contributor. The annotation of structurally diverse metabolites, including roquefortines, viridicatin derivatives, andrastins, and multiple diketopiperazines, highlights the metabolic plasticity of Antarctic fungi. Anticancer evaluation indicated cytotoxicity, with Aspergillus awamori (A30), Alternaria malorum (A36), and Cladosporium malorum (A38) displaying activity toward HCT 116 colorectal cancer cells at IC50 \u2265 30 \u00b5g\/mL. Extracts were screened against methicillin-resistant Staphylococcus aureus (MRSA, COL), methicillin-susceptible S. aureus (MSSA, NCTC8325 4), and Escherichia coli K12, revealing low to no activity against these pathogens. Six of the nine isolates exhibited strong antibiofilm activity without inhibiting planktonic bacterial growth, indicating selective biofilm inhibition against MSSA and meeting the criteria for clinical developmental \u201chits\u201d. Biofilm inhibition ranged from 81.10% to 98.50%, with A15A showing the highest activity (98.50% at 250 \u00b5g\/mL), followed by A36 (91.16% at 31.35 \u00b5g\/mL). Botrytis sp. (A22A), P. chrysogenum (A7), Ulocladium microsporum (A24B), and A30 also demonstrated strong antibiofilm activity (81.10\u201385.89%). To our knowledge, this is the first report describing antibiofilm activity of Antarctic fungal extracts.<\/jats:p>","DOI":"10.3390\/md24080267","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:17:40Z","timestamp":1785737860000},"page":"267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antarctic Marine-Derived Fungi: Metabolomic Signatures and Antibiofilm-Driven Anti-Infective Potential Against Drug Resistant Pathogens"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5945-8743","authenticated-orcid":false,"given":"\u0130brahim S.","family":"Uras","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacognosy, A\u011fr\u0131 \u0130brahim \u00c7e\u00e7en University, 04100 A\u011fr\u0131, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro H. S.","family":"Candido","sequence":"additional","affiliation":[{"name":"Department of Fundamental Chemistry, Institute of Chemistry, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0733-999X","authenticated-orcid":false,"given":"Catarina M.","family":"Lu\u00eds","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University of Lisbon, Campus Caparica, 2819-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Chemistry and Life Sciences Departments, NOVA School of Science and Technology, NOVA University of Lisbon, Campus Caparica, 2819-516 Caparica, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanda","family":"Marques","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. 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