ATIVIDADE LEISHMANICIDA DE FRAÇÃO FÚNGICA OBTIDA DE Fusarium solani

Abstract

Introduction: Cutaneous Leishmaniasis is an infectious disease caused by parasites of the Leishmania genus, transmitted through the bite of female phlebotomine sandflies. It presents high prevalence in low-income regions and is closely linked to social and economic inequalities. In the state of Maranhão, an endemic area for the disease, 26.821 new cases were reported in 2024 alone, despite considerable underreporting. Recent studies have highlighted several limitations associated with the currently available treatments (pentavalent antimonials® and Amphotericin B®) including severe adverse effects (nephrotoxicity and hepatotoxicity) and the increasing resistance of the parasites. Given these limitations, the development of new therapeutic strategies is urgently needed. Among the alternatives, fungal extracts have emerged as a promising field of study. In this context, the Fusarium genus is noteworthy for its brad capacity to synthesize secondary metabolites, which possess not only antibacterial but also antiviral properties, expanding their potential pharmacological applications. Objective: To evaluate the antiparasitic and immunomodulatory activity of fungal extracts from Fusarium solani. Methodology: The fungal extract was obtained from a strain of Fusarium solani (SISGEN Registration Nº A6461DC), isolated from the fungal collection of the Basic and Applied Immunology Center (NIBA) at the Universidade Federal do Maranhão (UFMA). The crude extract was subjected to fractionation through liquid-liquid partition using ethyl acetate and methanol as solvents. To assess its biological properties, cytotoxicity assays were perfomed on the murine macrophage cell line RAW 264.7, in addition to leishmanicidal activity tests against promastigotes forms of Leishmania amazonensis. Furthermore, immunomodulatory activity was evaluated by quantifying of the metabolites present in the extract was carried out using High-Performance Liquid Chromatography (HPLC). Results: HPLC analysis revealed a complex chemical profile, with multiple peaks indicative of bioactive compounds. Although definitive structural identification requires further analyses, previous studies on the Fusarium genus suggests the possible presence of chemical groups such as flavonoids, alkaloids and flavanones. Cytotoxicity assays showed that the ethyl acetate-methanol fraction of F. solani (Methanol-AcOEt) exhibited low cytotoxicity toward RAW 264.7 macrophages, with the CC50 value of 3.341µg/mL. Conversely, the AcOEt-Methanol fraction from F. solani demonstrated significant leishmanicidal activity against L. amazonensis promastigotes, with an IC50, was higher than 1, indicating selective toxicity against the parasite over the host cells. Additionally, increased NO production was observed in treated macrophages, suggesting a potential immunomodulatory effect associated with the fraction. Conclusion: The results indicate that AcOEt-Methanol fraction not only possesses promising leishmanicidal activity but also demonstrates the ability to modulate the innate immune response. Therefore, the fraction and its extracted secondary metabolites are promising candidates for the development of new therapeutic approaches against leishmaniasis.