Bioprospecting of Bioactive Secondary Metabolites of Endophytic Fungi of Carapichea ipecacuanha (Rubiaceae), a Neotropical Medicinal Species

Abstract

The discovery of new bioactive metabolites has become a focus of study in the search for highly efficient methods for the prevention, control, and treatment of several tropical diseases, such as visceral leishmaniasis and Chagas disease. In addition to new medicinal products, bioactive molecules show promise as natural herbicides for use in agriculture and therefore represent an alternative to the synthetic herbicides, which are toxic to humans and animals and difficult to degrade. Endophytic fungi may produce bioactive metabolites of commercial interest for use in both medicine and agriculture. Carapichea ipecacuanha (Brot.) L. Andersson (Rubiaceae), found in the tropical forests of South America, is a medicinal plant with emetic and amebicidal properties and, therefore, a promising target for the study of its community of endophytic fungi. This study aimed to evaluate the secondary metabolites of endophytic fungi associated with C. ipecacuanha for activity against the causative parasites of neglected tropical diseases and herbicidal activity for potential use in agriculture. From 275 endophytic fungi obtained from the leaves, stems, and roots of C. ipecacuanha, 15 isolates of the genera Colletotrichum, Diaporthe, Leptobacillium, Calonectria, and Trichoderma showed promising activities against the parasites Trypanosoma cruzi and Leishmania amazonensis and herbicidal activities. The extract produced from the isolated fungal sp. UFMGCB 15290 showed leishmanicidal activity with 73% inhibition and IC₅₀ of 0.3783 mg mL⁻¹. The extract of fungal sp. UFMGCB 15290 showed IC₅₀ of 42 μg mL⁻¹ against an intracellular form of the parasite in THP-1 cells and IC₅₀ of >100 μg mL⁻¹ against the cells. Against T. cruzi, the extracts of Leptobacillium sp. UFMGCB 15183 and Diaporthe sp. UFMGCB 15195 showed the lowest IC₅₀ values, 2.3 and 3.5 μg mL⁻¹, respectively. The extract from Diaporthe sp. UFMGCB 15138 showed an IC₅₀ of 7.5 μg mL⁻¹ against the intracellular parasite and 40 μg mL⁻¹ against the cells. The extract of Diaporthe sp. UFMGCB 15087 yielded the highest IC₅₀ value in the host cell (80 μg mL⁻¹) and the highest selectivity index (10.9). Additionally, the extract of Diaporthe sp. UFMGCB 15138 was characterized through fractionation using ultrahigh-pressure liquid chromatography-mass spectrometry. The active compound detected had the molecular formula C₃₉H₄₀O₁₅ and molecular weight of 750.6987 g mol⁻¹ and was identified as a xanthone dimer, either dicerandrol C or phomoxanthone B, which may be responsible for the biological activity. The results obtained in this study demonstrate that the plant C. ipecacuanha is a natural reservoir of endophytic fungi producing bioactive substances, especially those with herbicidal activities and acting against agents that cause NTDs. Therefore, endophytic fungi can be considered good candidates for in-depth chemical studies on the isolation and characterization of active substances capable of treating NTDs and for use as herbicides in agriculture.