Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus <i>Fusarium</i> sp. Associated with <i>Dizygostemon riparius</i> (Plantaginaceae)

<b>Background/Objectives</b>: 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 <i>Fusarium</i> sp. isolated from <i>Dizygostemo...

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Main Authors: Hilzimar de Jesus Freitas Sá, Anne Karoline Maiorana Santos, Adriano Souza Fonseca, Lourivaldo da Silva Santos, Josivan Regis Farias, Rosane Nassar Meireles Guerra, Edson Rodrigues-Filho, Gilmar Silverio da Silva, Cleydlenne Costa Vasconcelos, Alberto Jorge Oliveira Lopes, Antônio José Cantanhede Filho
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Language:English
Published: MDPI AG 2025-07-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/15/7/451
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author Hilzimar de Jesus Freitas Sá
Anne Karoline Maiorana Santos
Adriano Souza Fonseca
Lourivaldo da Silva Santos
Josivan Regis Farias
Rosane Nassar Meireles Guerra
Edson Rodrigues-Filho
Gilmar Silverio da Silva
Cleydlenne Costa Vasconcelos
Alberto Jorge Oliveira Lopes
Antônio José Cantanhede Filho
author_facet Hilzimar de Jesus Freitas Sá
Anne Karoline Maiorana Santos
Adriano Souza Fonseca
Lourivaldo da Silva Santos
Josivan Regis Farias
Rosane Nassar Meireles Guerra
Edson Rodrigues-Filho
Gilmar Silverio da Silva
Cleydlenne Costa Vasconcelos
Alberto Jorge Oliveira Lopes
Antônio José Cantanhede Filho
author_sort Hilzimar de Jesus Freitas Sá
collection DOAJ
description <b>Background/Objectives</b>: 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 <i>Fusarium</i> sp. isolated from <i>Dizygostemon riparius</i>, with particular focus on the impact of culture medium supplementation with halogenated and metallic additives on metabolite production. <b>Methods</b>: The fungus was cultivated in standard Czapek medium and media supplemented with NH<sub>4</sub>Br or MnCl<sub>2</sub>. 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 <i>Candida albicans</i> strains. In vivo toxicity and efficacy were assessed using <i>Tenebrio molitor</i> larvae. <b>Results</b>: 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. <b>Conclusions</b>: The results indicate that culture medium modulation enhances the production of bioactive metabolites by <i>Fusarium</i> 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 <i>Candida</i> infections. These findings support the potential of endophytic fungi as sources of novel therapeutics and warrant further mechanistic and pharmacological investigations.
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spelling doaj-art-e5893222b96246f193bc1fe6e7d47b0f2025-08-20T03:58:26ZengMDPI AGMetabolites2218-19892025-07-0115745110.3390/metabo15070451Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus <i>Fusarium</i> sp. Associated with <i>Dizygostemon riparius</i> (Plantaginaceae)Hilzimar de Jesus Freitas Sá0Anne Karoline Maiorana Santos1Adriano Souza Fonseca2Lourivaldo da Silva Santos3Josivan Regis Farias4Rosane Nassar Meireles Guerra5Edson Rodrigues-Filho6Gilmar Silverio da Silva7Cleydlenne Costa Vasconcelos8Alberto Jorge Oliveira Lopes9Antônio José Cantanhede Filho10Chemistry Postgraduate Program, Federal Institute of Science Education and Technology of Maranhão, São Luís 65030-005, BrazilChemistry Postgraduate Program, Federal Institute of Science Education and Technology of Maranhão, São Luís 65030-005, BrazilInstitute of Chemistry of Araraquara, São Paulo State University, Araraquara 14800-060, BrazilInstitute of Exact and Natural Sciences, Federal University of Pará, Belém 66075-110, BrazilCenter for Biological and Health Sciences, Federal University of Maranhão, São Luís 65030-005, BrazilCenter for Biological and Health Sciences, Federal University of Maranhão, São Luís 65030-005, BrazilMicromolecular Biochemistry of Microorganisms Laboratory (LaBioMMi), Department of Chemistry, Center for Exact Sciences and Technology, Federal University of São Carlos, São Carlos 13563-120, BrazilChemistry Postgraduate Program, Federal Institute of Science Education and Technology of Maranhão, São Luís 65030-005, BrazilCenter for Biological and Health Sciences, Federal University of Maranhão, São Luís 65030-005, BrazilChemistry Postgraduate Program, Federal Institute of Science Education and Technology of Maranhão, São Luís 65030-005, BrazilChemistry Postgraduate Program, Federal Institute of Science Education and Technology of Maranhão, São Luís 65030-005, Brazil<b>Background/Objectives</b>: 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 <i>Fusarium</i> sp. isolated from <i>Dizygostemon riparius</i>, with particular focus on the impact of culture medium supplementation with halogenated and metallic additives on metabolite production. <b>Methods</b>: The fungus was cultivated in standard Czapek medium and media supplemented with NH<sub>4</sub>Br or MnCl<sub>2</sub>. 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 <i>Candida albicans</i> strains. In vivo toxicity and efficacy were assessed using <i>Tenebrio molitor</i> larvae. <b>Results</b>: 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. <b>Conclusions</b>: The results indicate that culture medium modulation enhances the production of bioactive metabolites by <i>Fusarium</i> 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 <i>Candida</i> infections. These findings support the potential of endophytic fungi as sources of novel therapeutics and warrant further mechanistic and pharmacological investigations.https://www.mdpi.com/2218-1989/15/7/451secondary metabolitesbiofilm inhibitionnatural product discoveryhalogen and metal supplementation
spellingShingle Hilzimar de Jesus Freitas Sá
Anne Karoline Maiorana Santos
Adriano Souza Fonseca
Lourivaldo da Silva Santos
Josivan Regis Farias
Rosane Nassar Meireles Guerra
Edson Rodrigues-Filho
Gilmar Silverio da Silva
Cleydlenne Costa Vasconcelos
Alberto Jorge Oliveira Lopes
Antônio José Cantanhede Filho
Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus <i>Fusarium</i> sp. Associated with <i>Dizygostemon riparius</i> (Plantaginaceae)
Metabolites
secondary metabolites
biofilm inhibition
natural product discovery
halogen and metal supplementation
title Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus <i>Fusarium</i> sp. Associated with <i>Dizygostemon riparius</i> (Plantaginaceae)
title_full Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus <i>Fusarium</i> sp. Associated with <i>Dizygostemon riparius</i> (Plantaginaceae)
title_fullStr Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus <i>Fusarium</i> sp. Associated with <i>Dizygostemon riparius</i> (Plantaginaceae)
title_full_unstemmed Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus <i>Fusarium</i> sp. Associated with <i>Dizygostemon riparius</i> (Plantaginaceae)
title_short Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus <i>Fusarium</i> sp. Associated with <i>Dizygostemon riparius</i> (Plantaginaceae)
title_sort assessment of metabolic alterations induced by halogenated additives and antifungal activity of extracts from the endophytic fungus i fusarium i sp associated with i dizygostemon riparius i plantaginaceae
topic secondary metabolites
biofilm inhibition
natural product discovery
halogen and metal supplementation
url https://www.mdpi.com/2218-1989/15/7/451
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