{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:27:56Z","timestamp":1760059676402,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES, PROCAD-AM)","award":["88887.311086\/2018-00","13\/2020","PAEDT-03230\/17","IECT-NATU-MED-02885\/17","2019\/04900-2","405940\/2021-1"],"award-info":[{"award-number":["88887.311086\/2018-00","13\/2020","PAEDT-03230\/17","IECT-NATU-MED-02885\/17","2019\/04900-2","405940\/2021-1"]}]},{"name":"Development of Postgraduate Studies in the Legal Amazon (Notice\/CAPES)","award":["88887.311086\/2018-00","13\/2020","PAEDT-03230\/17","IECT-NATU-MED-02885\/17","2019\/04900-2","405940\/2021-1"],"award-info":[{"award-number":["88887.311086\/2018-00","13\/2020","PAEDT-03230\/17","IECT-NATU-MED-02885\/17","2019\/04900-2","405940\/2021-1"]}]},{"name":"Support Research and Scientific and Technological Development of Maranh\u00e3o (FAPEMA)","award":["88887.311086\/2018-00","13\/2020","PAEDT-03230\/17","IECT-NATU-MED-02885\/17","2019\/04900-2","405940\/2021-1"],"award-info":[{"award-number":["88887.311086\/2018-00","13\/2020","PAEDT-03230\/17","IECT-NATU-MED-02885\/17","2019\/04900-2","405940\/2021-1"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["88887.311086\/2018-00","13\/2020","PAEDT-03230\/17","IECT-NATU-MED-02885\/17","2019\/04900-2","405940\/2021-1"],"award-info":[{"award-number":["88887.311086\/2018-00","13\/2020","PAEDT-03230\/17","IECT-NATU-MED-02885\/17","2019\/04900-2","405940\/2021-1"]}]},{"name":"National Council for Scientific and Technological Development (CNPq)","award":["88887.311086\/2018-00","13\/2020","PAEDT-03230\/17","IECT-NATU-MED-02885\/17","2019\/04900-2","405940\/2021-1"],"award-info":[{"award-number":["88887.311086\/2018-00","13\/2020","PAEDT-03230\/17","IECT-NATU-MED-02885\/17","2019\/04900-2","405940\/2021-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Endophytic fungi are valuable sources of bioactive compounds with potential therapeutic applications. This study aimed to evaluate the antifungal activity of secondary metabolites produced by Fusarium sp. isolated from Dizygostemon riparius, with particular focus on the impact of culture medium supplementation with halogenated and metallic additives on metabolite production. Methods: The fungus was cultivated in standard Czapek medium and media supplemented with NH4Br or MnCl2. Methanolic extracts were obtained, fractionated, and chemically characterised via LC-ESI-HRMS. In vitro antifungal assays, including MIC and MFC determinations and biofilm inhibition tests, were performed against Candida albicans strains. In vivo toxicity and efficacy were assessed using Tenebrio molitor larvae. Results: Fifteen metabolites were annotated, including known antifungals such as fusaric acid and cyclosporin A. Fractions EMBr4 and EMC5 demonstrated fungicidal activity with MIC values close to fluconazole and significantly inhibited biofilm formation and maturation. In vivo, these fractions displayed low acute toxicity and improved survival in infected larvae, comparable to fluconazole treatment. Conclusions: The results indicate that culture medium modulation enhances the production of bioactive metabolites by Fusarium sp., leading to extracts with notable antifungal efficacy and safety. EMBr4 and EMC5 are promising candidates for further development as antifungal agents, particularly for targeting biofilm-associated Candida infections. These findings support the potential of endophytic fungi as sources of novel therapeutics and warrant further mechanistic and pharmacological investigations.<\/jats:p>","DOI":"10.3390\/metabo15070451","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T05:54:52Z","timestamp":1751608492000},"page":"451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus Fusarium sp. Associated with Dizygostemon riparius (Plantaginaceae)"],"prefix":"10.3390","volume":"15","author":[{"given":"Hilzimar","family":"de Jesus Freitas S\u00e1","sequence":"first","affiliation":[{"name":"Chemistry Postgraduate Program, Federal Institute of Science Education and Technology of Maranh\u00e3o, S\u00e3o Lu\u00eds 65030-005, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Karoline Maiorana","family":"Santos","sequence":"additional","affiliation":[{"name":"Chemistry Postgraduate Program, Federal Institute of Science Education and Technology of Maranh\u00e3o, S\u00e3o Lu\u00eds 65030-005, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriano Souza","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Institute of Chemistry of Araraquara, S\u00e3o Paulo State University, Araraquara 14800-060, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourivaldo","family":"da Silva Santos","sequence":"additional","affiliation":[{"name":"Institute of Exact and Natural Sciences, Federal University of Par\u00e1, Bel\u00e9m 66075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josivan Regis","family":"Farias","sequence":"additional","affiliation":[{"name":"Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65030-005, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosane Nassar Meireles","family":"Guerra","sequence":"additional","affiliation":[{"name":"Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65030-005, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edson","family":"Rodrigues-Filho","sequence":"additional","affiliation":[{"name":"Micromolecular Biochemistry of Microorganisms Laboratory (LaBioMMi), Department of Chemistry, Center for Exact Sciences and Technology, Federal University of S\u00e3o Carlos, S\u00e3o Carlos 13563-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilmar Silverio","family":"da Silva","sequence":"additional","affiliation":[{"name":"Chemistry Postgraduate Program, Federal Institute of Science Education and Technology of Maranh\u00e3o, S\u00e3o Lu\u00eds 65030-005, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cleydlenne Costa","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Center for Biological and Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65030-005, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5267-9500","authenticated-orcid":false,"given":"Alberto Jorge Oliveira","family":"Lopes","sequence":"additional","affiliation":[{"name":"Chemistry Postgraduate Program, Federal Institute of Science Education and Technology of Maranh\u00e3o, S\u00e3o Lu\u00eds 65030-005, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2009-2817","authenticated-orcid":false,"given":"Ant\u00f4nio Jos\u00e9","family":"Cantanhede Filho","sequence":"additional","affiliation":[{"name":"Chemistry Postgraduate Program, Federal Institute of Science Education and Technology of Maranh\u00e3o, S\u00e3o Lu\u00eds 65030-005, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4103\/ijmm.IJMM_16_24","article-title":"Fusarium: The Versatile Pathogen","volume":"36","author":"Kindo","year":"2018","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s10658-024-02975-1","article-title":"Fusarium Species Associated with Naturally Regenerated Fagus Sylvatica Seedlings Affected by Phytophthora","volume":"171","author":"Jankowiak","year":"2025","journal-title":"Eur. J. Plant Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Todorovi\u0107, I., Mo\u00ebnne-Loccoz, Y., Rai\u010devi\u0107, V., Jovi\u010di\u0107-Petrovi\u0107, J., and Muller, D. (2023). Microbial Diversity in Soils Suppressive to Fusarium Diseases. Front. Plant Sci., 14.","DOI":"10.3389\/fpls.2023.1228749"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"853","DOI":"10.21577\/1984-6835.20220041","article-title":"OSMAC Strategy: An Affordable Method for the Discovery of New Microbial Compounds","volume":"14","author":"Hamerski","year":"2022","journal-title":"Rev. Virtual Qu\u00edmica"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Santos, A.K.M., dos Santos, B.A., Farias, J.R., de Morais, S.V., Vasconcelos, C.C., Guerra, R.N.M., Rodrigues-Filho, E., Lopes, A.J.O., and Cantanhede Filho, A.J. (2024). Effect of Mn(II) and Co(II) on Anti-Candida Metabolite Production by Aspergillus sp. an Endophyte Isolated from Dizygostemon Riparius (Plantaginaceae). Pharmaceuticals, 17.","DOI":"10.3390\/ph17121678"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/s12934-024-02567-y","article-title":"Tailored Culture Strategies to Promote Antimicrobial Secondary Metabolite Production in Diaporthe Caliensis: A Metabolomic Approach","volume":"23","author":"Hoyos","year":"2024","journal-title":"Microb. Cell Fact."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Michaliski, L.F., I\u00f3ca, L.P., Oliveira, L.S., Crnkovic, C.M., Takaki, M., Freire, V.F., and Berlinck, R.G.S. (2023). Improvement of Targeted Fungi Secondary Metabolite Production Using a Systematic Experimental Design and Chemometrics Analysis. Methods Protoc., 6.","DOI":"10.3390\/mps6050077"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"39873","DOI":"10.1021\/acsomega.3c06299","article-title":"OSMAC Approach and Cocultivation for the Induction of Secondary Metabolism of the Fungus Pleotrichocladium Opacum","volume":"8","author":"Cuadrado","year":"2023","journal-title":"ACS Omega"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Karaffa, L., Fekete, E., and Kubicek, C.P. (2021). The Role of Metal Ions in Fungal Organic Acid Accumulation. Microorganisms, 9.","DOI":"10.3390\/microorganisms9061267"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ekwomadu, T.I., and Mwanza, M. (2023). Fusarium Fungi Pathogens, Identification, Adverse Effects, Disease Management, and Global Food Security: A Review of the Latest Research. Agriculture, 13.","DOI":"10.3390\/agriculture13091810"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ibrahim, S.R.M., Sirwi, A., Eid, B.G., Mohamed, S.G.A., and Mohamed, G.A. (2021). Bright Side of Fusarium Oxysporum: Secondary Metabolites Bioactivities and Industrial Relevance in Biotechnology and Nanotechnology. J. Fungi, 7.","DOI":"10.3390\/jof7110943"},{"key":"ref_12","first-page":"2622","article-title":"An Extracellular Lipase from the Endophytic Fungi Fusarium Oxysporum Isolated from the Thai Medicinal Plant, Croton Oblongifolius Roxb","volume":"6","author":"Panuthai","year":"2012","journal-title":"Afr. J. Microbiol. Res."},{"key":"ref_13","first-page":"358140","article-title":"Screening of Fusarium Graminearum Isolates for Enzymes Extracellular and Deoxynivalenol Production","volume":"2013","author":"Ortega","year":"2013","journal-title":"J. Mycol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"de Oliveira Santos, G.C., Vasconcelos, C.C., Lopes, A.J., de Sousa Cart\u00e1genes, M.D., Filho, A.K., do Nascimento, F.R., Ramos, R.M., Pires, E.R., de Andrade, M.S., and Rocha, F.M. (2018). Candida Infections and Therapeutic Strategies: Mechanisms of Action for Traditional and Alternative Agents. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01351"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Silva, A.F., Farias, J.R., Franco, D.C., Galiza, A.A., Motta, E.P., Oliveira, A.D., Vasconcelos, C.C., Cart\u00e1genes, M.D., Rocha, C.Q., and Silva, M.C. (2022). Anti-Candida Albicans Activity of Ononin and Other Secondary Metabolites from Platonia Insignis MART. Metabolites, 12.","DOI":"10.3390\/metabo12111014"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Motta, E.P., Farias, J.R., Costa, A.A., Silva, A.F., Oliveira Lopes, A.J., Cart\u00e1genes, M.D., Nicolete, R., Abreu, A.G., Fernandes, E.S., and Nascimento, F.R. (2022). The Anti-Virulence Effect of Vismia Guianensis against Candida Albicans and Candida Glabrata. Antibiotics, 11.","DOI":"10.3390\/antibiotics11121834"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"429","DOI":"10.4014\/jmb.1608.08024","article-title":"Antimicrobial Activity of Basil, Oregano, and Thyme Essential Oils","volume":"27","author":"Sakkas","year":"2017","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1099\/00207713-16-3-313","article-title":"Methods for Characterization of Streptomyces Species","volume":"16","author":"Shirling","year":"1966","journal-title":"Int. J. Syst. Bacteriol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1590\/S0102-695X2010000400026","article-title":"Secagem Por Aspers\u00e3o (Spray Drying) de Extratos Vegetais: Bases e Aplica\u00e7\u00f5es","volume":"20","author":"Oliveira","year":"2010","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s00216-015-9110-7","article-title":"Multi-Mycotoxin Stable Isotope Dilution LC-MS\/MS Method for Fusarium Toxins in Cereals","volume":"408","author":"Habler","year":"2016","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_21","unstructured":"CLSI (2017). Reference Method For Broth Dilution Antifungal Susceptibility Testing Of Yeasts (Approved Standard. M27-A3), Clinical and Laboratory Standards Institute. [3rd ed.]."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jscs.2011.03.016","article-title":"Synthesis, Characterization and Antimicrobial Evaluation of Novel Halopyrazole Derivatives","volume":"17","author":"Siddiqui","year":"2013","journal-title":"J. Saudi Chem. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"da Silva, A.F., da Rocha, C.Q., da Silva, L.C., Carvalho J\u00fanior, A.R., Mendes, I.N., de Araruna, A.B., Motta, E.P., Silva, R.D., Campos, C.D., and Farias, J.R. (2020). Antifungal and Antivirulence Activities of Hydroalcoholic Extract and Fractions of Platonia Insignis Leaves against Vaginal Isolates of Candida Species. Pathogens, 9.","DOI":"10.3390\/pathogens9020084"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Seneviratne, C.J., Rajan, S., Wong, S.S.W., Tsang, D.N.C., Lai, C.K.C., Samaranayake, L.P., and Jin, L. (2016). Antifungal Susceptibility in Serum and Virulence Determinants of Candida Bloodstream Isolates from Hong Kong. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00216"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1128\/AAC.01846-15","article-title":"Berberine Antifungal Activity in Fluconazole-Resistant Pathogenic Yeasts: Action Mechanism Evaluated by Flow Cytometry and Biofilm Growth Inhibition in Candida spp.","volume":"60","author":"Campos","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zago, C.E., Silva, S., Sanit\u00e1, P.V., Barbugli, P.A., Dias, C.M.I., Lordello, V.B., and Vergani, C.E. (2015). Dynamics of Biofilm Formation and the Interaction between Candida Albicans and Methicillin-Susceptible (MSSA) and -Resistant Staphylococcus Aureus (MRSA). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123206"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.mimet.2015.10.004","article-title":"Tenebrio Molitor (Coleoptera: Tenebrionidae) as an Alternative Host to Study Fungal Infections","volume":"118","author":"Morey","year":"2015","journal-title":"J. Microbiol. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ogofure, A.G., Pelo, S.P., and Green, E. (2024). Identification and Assessment of Secondary Metabolites from Three Fungal Endophytes of Solanum Mauritianum Against Public Health Pathogens. Molecules, 29.","DOI":"10.3390\/molecules29204924"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/j.1365-2672.2007.03581.x","article-title":"Bikaverin and Fusaric Acid from Fusarium Oxysporum Show Antioomycete Activity against Phytophthora Infestans","volume":"104","author":"Son","year":"2008","journal-title":"J. Appl. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/10575639508043166","article-title":"Three Diketopiperazines from the Cultivated Fungus Fusarium Oxysporum","volume":"6","author":"Trigos","year":"1995","journal-title":"Nat. Prod. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Alfattani, A., Marcourt, L., Hofstetter, V., Queiroz, E.F., Leoni, S., Allard, P.-M., Gindro, K., Stien, D., Perron, K., and Wolfender, J.-L. (2021). Combination of Pseudo-LC-NMR and HRMS\/MS-Based Molecular Networking for the Rapid Identification of Antimicrobial Metabolites From Fusarium Petroliphilum. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.725691"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1365-2672.2005.02824.x","article-title":"Cyclosporine A from a Nonpathogenic Fusarium Oxysporum Suppressing Sclerotinia Sclerotiorum","volume":"100","author":"Rodriguez","year":"2006","journal-title":"J. Appl. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fitote.2019.01.016","article-title":"Fusariumins C and D, Two Novel Antimicrobial Agents from Fusarium Oxysporum ZZP-R1 Symbiotic on Rumex Madaio Makino","volume":"134","author":"Chen","year":"2019","journal-title":"Fitoterapia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1139\/m67-181","article-title":"Sterol and Fatty Acid Components of Mycelium of Fusarium Oxysporum","volume":"13","author":"Starratt","year":"1967","journal-title":"Can. J. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1080\/03235408.2021.1973848","article-title":"Identification of Secondary Metabolites in Mycoparasites Fusarium Strains and Antifungal Activity of Fusaric Acid against Plasmopara Viticola","volume":"55","author":"Ghule","year":"2022","journal-title":"Arch. Phytopathol. Plant Prot."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1021\/np050487v","article-title":"N -Methyl-4-Hydroxy-2-Pyridinone Analogues from Fusarium Oxysporum","volume":"69","author":"Jayasinghe","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"105710","DOI":"10.1016\/j.fitote.2023.105710","article-title":"The Antifungal Metabolites Isolated from Maize Endophytic Fungus Fusarium Sp. Induced by OSMAC Strategy","volume":"171","author":"Sun","year":"2023","journal-title":"Fitoterapia"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"He, T., Li, X., Iacovelli, R., Hackl, T., and Haslinger, K. (2023). Genomic and Metabolomic Analysis of the Endophytic Fungus Fusarium Sp. VM-40 Isolated from the Medicinal Plant Vinca Minor. J. Fungi, 9.","DOI":"10.3390\/jof9070704"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0031-9422(02)00128-0","article-title":"Isofuranonaphthoquinone Derivatives from Cultures of the Lichen Arthonia Cinnabarina (DC.) Wallr.","volume":"60","author":"Yamamoto","year":"2002","journal-title":"Phytochemistry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3761","DOI":"10.1016\/S0031-9422(00)97523-X","article-title":"Phytoalexins, Benzoxazinones, N-Aroylanthranilates and N-Aroylanilines, from Fusarium-Infected Carnation Stems","volume":"31","author":"Niemann","year":"1992","journal-title":"Phytochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1128\/aem.55.1.254-255.1989","article-title":"Mycotoxin Production by Fusarium Oxysporum and Fusarium Sporotrichioides Isolated from Baccharis spp. from Brazil","volume":"55","author":"Mirocha","year":"1989","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0031-9422(98)00596-2","article-title":"Jasmonates and Related Compounds from Fusarium Oxysporum","volume":"50","author":"Miersch","year":"1999","journal-title":"Phytochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9105","DOI":"10.1007\/s00253-018-9344-3","article-title":"Endophytic Fungi Isolated from Medicinal Plants: Future Prospects of Bioactive Natural Products from Tabebuia\/Handroanthus Endophytes","volume":"102","author":"Luiz","year":"2018","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wen, J., Okyere, S.K., Wang, S., Wang, J., Xie, L., Ran, Y., and Hu, Y. (2022). Endophytic Fungi: An Effective Alternative Source of Plant-Derived Bioactive Compounds for Pharmacological Studies. J. Fungi, 8.","DOI":"10.3390\/jof8020205"},{"key":"ref_45","first-page":"e01594","article-title":"A Review on the Trends of Endophytic Fungi Bioactivities","volume":"20","author":"Omomowo","year":"2023","journal-title":"Sci. Afr."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Caruso, D.J., Palombo, E.A., Moulton, S.E., and Zaferanloo, B. (2022). Exploring the Promise of Endophytic Fungi: A Review of Novel Antimicrobial Compounds. Microorganisms, 10.","DOI":"10.3390\/microorganisms10101990"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Huang, B.B., Liu, Y.Y., Zhu, P.F., Jiang, Y.C., and Ouyang, M.-A. (2020). Concise Total Synthesis and Antifungal Activities of Fusaric Acid, a Natural Product. Molecules, 25.","DOI":"10.3390\/molecules25173859"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"18566","DOI":"10.1021\/acs.jafc.3c04720","article-title":"Design, Synthesis, Structure\u2013Activity Relationship, and Three-Dimensional Quantitative Structure\u2013Activity Relationship of Fusarium Acid Derivatives and Analogues as Potential Fungicides","volume":"71","author":"Huang","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mac\u00edas-Rubalcava, M.L., Lappe-Oliveras, P., and Villanueva-Silva, R. (2025). Disruption of Cell Wall and Membrane Integrity as Antioomycete and Antifungal Mode of Action by Fusaric and 9,10-Dehydrofusaric Acids from Endophytic Fungus Fusarium Lactis Strain SME13-2. J. Appl. Microbiol., 136.","DOI":"10.1093\/jambio\/lxae301"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"124593","DOI":"10.1016\/j.ijpharm.2024.124593","article-title":"Synergistic Antifungal Activity against Candida Albicans between Voriconazole and Cyclosporine a Loaded in Polymeric Nanoparticles","volume":"664","author":"Bernal","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Li, F., Lv, Z., Zhong, Z., Mao, L., Chua, L.S., Xu, L., and Huang, R. (2023). The Effect of Cyclosporin A on Aspergillus Niger and the Possible Mechanisms Involved. Foods, 12.","DOI":"10.3390\/foods12030567"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"de Andrade, I.B., Corr\u00eaa-Junior, D., Alves, V., Figueiredo-Carvalho, M.H.G., Santos, M.V., Almeida, M.A., Valdez, A.F., Nimrichter, L., Almeida-Paes, R., and Frases, S. (2023). Cyclosporine Affects the Main Virulence Factors of Cryptococcus Neoformans In Vitro. J. Fungi, 9.","DOI":"10.3390\/jof9040487"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1093\/jac\/dkm493","article-title":"In Vitro Interaction between Azoles and Cyclosporin A against Clinical Isolates of Candida Albicans Determined by the Chequerboard Method and Time-Kill Curves","volume":"61","author":"Li","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Xu, M., Huang, Z., Zhu, W., Liu, Y., Bai, X., and Zhang, H. (2023). Fusarium-Derived Secondary Metabolites with Antimicrobial Effects. Molecules, 28.","DOI":"10.3390\/molecules28083424"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1080\/14786419.2015.1095747","article-title":"Antibacterial Activity of Cyclo(L-Pro-L-Tyr) and Cyclo(D-Pro-L-Tyr) from Streptomyces Sp. Strain 22-4 against Phytopathogenic Bacteria","volume":"30","author":"Charoenwongsa","year":"2016","journal-title":"Nat. Prod. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"107048","DOI":"10.1016\/j.isci.2023.107048","article-title":"Effects of Hydroxyl Group in Cyclo(Pro-Tyr)-like Cyclic Dipeptides on Their Anti-QS Activity and Self-Assembly","volume":"26","author":"Li","year":"2023","journal-title":"iScience"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s12088-010-0056-3","article-title":"Antimicrobial Endophytic Fungal Assemblages Inhabiting Bark of Taxus baccata L. of Indo-Burma Mega Biodiversity Hotspot","volume":"50","author":"Tayung","year":"2010","journal-title":"Indian J. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Amuzu, P., Pan, X., Hou, X., Sun, J., Jakada, M.A., Odigie, E., Xu, D., Lai, D., and Zhou, L. (2024). Recent Updates on the Secondary Metabolites from Fusarium Fungi and Their Biological Activities (Covering 2019 to 2024). J. Fungi, 10.","DOI":"10.3390\/jof10110778"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Li, W.-S., Chen, Y.-C., Kuo, S.-F., Chen, F.-J., and Lee, C.-H. (2018). The Impact of Biofilm Formation on the Persistence of Candidemia. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01196"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Silva, S., Rodrigues, C., Ara\u00fajo, D., Rodrigues, M., and Henriques, M. (2017). Candida Species Biofilms\u2019 Antifungal Resistance. J. Fungi, 3.","DOI":"10.3390\/jof3010008"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Canteri de Souza, P., Cust\u00f3dio Caloni, C., Wilson, D., and Sergio Almeida, R. (2018). An Invertebrate Host to Study Fungal Infections, Mycotoxins and Antifungal Drugs: Tenebrio Molitor. J. Fungi, 4.","DOI":"10.3390\/jof4040125"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"107133","DOI":"10.1016\/j.micpath.2024.107133","article-title":"N -Butanol Fraction of Terminalia Catappa Possesses Anti-Candida Albicans Properties and in Vivo Action on Tenebrio Molitor Alternative Infection Model","volume":"198","author":"Rocha","year":"2025","journal-title":"Microb. Pathog."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4333","DOI":"10.1128\/IAI.71.8.4333-4340.2003","article-title":"Mechanism of Fluconazole Resistance in Candida Albicans Biofilms: Phase-Specific Role of Efflux Pumps and Membrane Sterols","volume":"71","author":"Mukherjee","year":"2003","journal-title":"Infect. Immun."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/7\/451\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:04:22Z","timestamp":1760033062000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/7\/451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,4]]},"references-count":63,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["metabo15070451"],"URL":"https:\/\/doi.org\/10.3390\/metabo15070451","relation":{},"ISSN":["2218-1989"],"issn-type":[{"type":"electronic","value":"2218-1989"}],"subject":[],"published":{"date-parts":[[2025,7,4]]}}}