Bioprospecting of Secondary Bioactive Metabolites Produced by Endophytic Fungi of the Medicinal Piper sp. in the Brazilian Tropical Rain Forest

Secondary metabolites, structurally heterogeneous and low-molecular-mass molecules produced by living organisms, stand out for their potential as useful prototypes in the development of new drugs. Endophytic fungi are potential producers of several bioactive metabolites that can be used as therapeutic agents in the treatment of various diseases. Plants of the Piperaceae family are distributed in the southern and northern hemispheres and are used in several ways. These plants are known for producing a great diversity of metabolites and are a promising reservoir for a great variety of endophytic fungi. Thus, the objective of this study was to evaluate the potential of the endophytic fungi community associated with Piper sp., collected from the largest fragment of the Atlantic Forest in the state of Minas Gerais, Brazil, as a source of active metabolites with herbicidal properties and activity in neglected diseases. From the stems, leaves, and roots, 540 fungi were obtained. To determine the biotechnological potential of fungi and their host plant, ethanolic extracts were produced, which were tested for antiparasitic, antiviral, and herbicidal activities. Of the 105 fungal isolates that showed promising biological activities, 52 were identified as members of Ascomycota, mostly represented by the genera Fusarium, Diaporthe, and Lasiodiplodia. This is the first study to report the herbicidal activity of endophytic fungi related to the genera Muscodor, Nigrospora, Phyllosticta, Pestalotiopsis, Neopestalotiopsis, Lasiodiplodia, Arthrinium, and Acrocalymma. Fusarium sp. UFMGCB 15603 showed antiviral activity against DENV-2 with an inhibition percentage of 76% and an EC50 of 10.5 μg mL−1. This is the first report of this activity in endophytic fungi of this genus. Twenty-three isolates showed promising biological activity against P. falciparum, with IC50 values ranging between 0.0071 μg mL−1 and 5.7 μg mL−1. Our results show that leaves, stems, and root tissues of medicinal Neotropical Piper sp. are a reservoir of potential new fungal species. Within the Piper sp. endophytic community, different taxa and strains are potential sources of secondary bioactive metabolites. In addition, Neotropical species of Piper can be considered a promising source of potential fungal producers of bioactive secondary prototype metabolites for the development of new drugs. These facts reinforce the importance of studies on plants and microorganisms present in the Brazilian ecosystem, as these can be sources of natural products with therapeutic and agricultural applications.