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

de Jesus Freitas Sá, Hilzimar; Santos, Anne Karoline Maiorana; Fonseca, Adriano Souza; da Silva Santos, Lourivaldo; Farias, Josivan Regis; Guerra, Rosane Nassar Meireles; Rodrigues-Filho, Edson; da Silva, Gilmar Silverio; Vasconcelos, Cleydlenne Costa; Lopes, Alberto Jorge Oliveira; Cantanhede Filho, Antônio José

doi:10.3390/metabo15070451

Open AccessArticle

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

by

Hilzimar de Jesus Freitas Sá

¹,

Anne Karoline Maiorana Santos

¹,

Adriano Souza Fonseca

²,

Lourivaldo da Silva Santos

³,

Josivan Regis Farias

⁴,

Rosane Nassar Meireles Guerra

⁴,

Edson Rodrigues-Filho

⁵,

Gilmar Silverio da Silva

¹,

Cleydlenne Costa Vasconcelos

⁴,

Alberto Jorge Oliveira Lopes

^1,*

and

Antônio José Cantanhede Filho

^1,*

¹

Chemistry Postgraduate Program, Federal Institute of Science Education and Technology of Maranhão, São Luís 65030-005, Brazil

²

Institute of Chemistry of Araraquara, São Paulo State University, Araraquara 14800-060, Brazil

³

Institute of Exact and Natural Sciences, Federal University of Pará, Belém 66075-110, Brazil

⁴

Center for Biological and Health Sciences, Federal University of Maranhão, São Luís 65030-005, Brazil

⁵

Micromolecular Biochemistry of Microorganisms Laboratory (LaBioMMi), Department of Chemistry, Center for Exact Sciences and Technology, Federal University of São Carlos, São Carlos 13563-120, Brazil

^*

Authors to whom correspondence should be addressed.

Metabolites 2025, 15(7), 451; https://doi.org/10.3390/metabo15070451

Submission received: 10 June 2025 / Revised: 27 June 2025 / Accepted: 1 July 2025 / Published: 4 July 2025

(This article belongs to the Special Issue Secondary Metabolites and Their Activities: From the Identification to the Biological Investigation)

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Abstract

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.

Keywords: secondary metabolites; biofilm inhibition; natural product discovery; halogen and metal supplementation

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MDPI and ACS Style

de Jesus Freitas Sá, H.; Santos, A.K.M.; Fonseca, A.S.; da Silva Santos, L.; Farias, J.R.; Guerra, R.N.M.; Rodrigues-Filho, E.; da Silva, G.S.; Vasconcelos, C.C.; Lopes, A.J.O.; et al. Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus Fusarium sp. Associated with Dizygostemon riparius (Plantaginaceae). Metabolites 2025, 15, 451. https://doi.org/10.3390/metabo15070451

AMA Style

de Jesus Freitas Sá H, Santos AKM, Fonseca AS, da Silva Santos L, Farias JR, Guerra RNM, Rodrigues-Filho E, da Silva GS, Vasconcelos CC, Lopes AJO, et al. Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus Fusarium sp. Associated with Dizygostemon riparius (Plantaginaceae). Metabolites. 2025; 15(7):451. https://doi.org/10.3390/metabo15070451

Chicago/Turabian Style

de Jesus Freitas Sá, Hilzimar, 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, and et al. 2025. "Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus Fusarium sp. Associated with Dizygostemon riparius (Plantaginaceae)" Metabolites 15, no. 7: 451. https://doi.org/10.3390/metabo15070451

APA Style

de Jesus Freitas Sá, H., Santos, A. K. M., Fonseca, A. S., da Silva Santos, L., Farias, J. R., Guerra, R. N. M., Rodrigues-Filho, E., da Silva, G. S., Vasconcelos, C. C., Lopes, A. J. O., & Cantanhede Filho, A. J. (2025). Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus Fusarium sp. Associated with Dizygostemon riparius (Plantaginaceae). Metabolites, 15(7), 451. https://doi.org/10.3390/metabo15070451

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

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