Endophytes have been shown to be a source of novel drug prototypes. The Casearia genus is known for presenting cytotoxic clerodane diterpenes; however, there are few reports on secondary metabolites produced by its fungal microbiota. Thus, in the present study endophytic fungi obtained from the fresh leaves of C. arborea were grown in potato dextrose broth and rice to perform a secondary metabolite prospection study. The cytotoxic profile of the crude extracts at 10 µg/mL was determined by a colorimetric assay on tumor cell lines. The endophytes producing cytotoxic extracts were identified through phylogenetic analysis and belong to Diaporthe and Colletotrichum species. Metabolites present in these extracts were organized in molecular networking format based on HRMS-MS, and a dereplication process was performed to target compounds for chromatographic purification. Metabolic classes, such as lipids, peptides, alkaloids, and polyketides were annotated, and octaketide and cytochalasin derivatives were investigated. Cytochalasin H was purified from the cytotoxic Diaporthe sp. CarGL8 extract and its cytotoxic activity was determined on human cancer cell lines A549, MCF-7, and HepG2. The data collected in the present study showed that molecular networking is useful to understand the chemical profile of complex matrices to target compounds, minimizing the cost and time spent in purification processes.

Endophytic fungi are increasingly being recognized for their diverse metabolites that may exhibit antimicrobial properties. In our study, we isolated seven endophytic fungal strains from Calea pinnatifida, which were identified as Hypomontagnella barbarensis, Neopestalotiopsis clavispora, Nigrospora sacchari-officinarum, Annulohypoxylon moriforme, Colletotrichum siamense, and Colletotrichum karstii (with two isolates from the same species). Furthermore, the antimicrobial activity of the extracts was assessed, revealing that the extract from Hypomontagnella barbarensis demonstrated activity against Staphylococcus aureus. Further investigation of secondary metabolites, employing UHPLC-HR-ESI-MS/MS in combination with molecular networking, facilitated annotation of the nine compounds. Of these, five were identified based on matches with the GNPS spectral library, and four were predicted based on the molecular network. Notably, from the extract of Hypomontagnella barbarensis, two pairs of diastereoisomeric acyl-tetronic acid derivatives were isolated and characterized using MS and NMR spectroscopy. This study highlights the potential of endophytic fungi as a valuable source of novel antimicrobial agents.

Corrigendum: (-)-T-Cadinol, a Sesquiterpene Isolated From Casearia sylvestris (Salicaceae)—Displayed In Vitro Activity and Causes Hyperpolarization of the Membrane Potential of Trypanosoma cruzi