Dereplication of Cytochalasans and Octaketides in Cytotoxic Extracts of Endophytic Fungi from <i>Casearia arborea</i> (Salicaceae)
2022
Augusto L. Santos | Marisa Ionta | Renato O. Horvath | Marisi G. Soares | Daniele O. Silva | Eunizinis S. Kawafune | Marcelo J. P. Ferreira | Patricia Sartorelli
Endophytes have been shown to be a source of novel drug prototypes. The <i>Casearia</i> 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 <i>C. arborea</i> 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 <i>Diaporthe</i> and <i>Colletotrichum</i> 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 <i>Diaporthe</i> 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.
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