Dereplication of Cytochalasans and Octaketides in Cytotoxic Extracts of Endophytic Fungi from Casearia arborea (Salicaceae)

Author(s)

Santos, Augusto L. ; Ionta, Marisa ; Horvath, Renato O. ; Soares, Marisi G. ; Silva, Daniele O. ; Kawafune, Eunizinis S. ; Ferreira, Marcelo J. P. ; Sartorelli, Patricia

• Document type: Journal article
• Source: METABOLITES; v. 12, n. 10, p. 12-pg., 2022-10-01.

Abstract

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 mu g/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. (AU)

• FAPESP's process: 20/16554-9 - Asteraceae and endophytic fungi: identification of natural products and biological activities
• Grantee: Marcelo José Pena Ferreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/24985-4 - Study the chemical composition of fungi and plants of the Atlantic Forest aimed at antitumor, antiparasitic and antimicrobial potential
• Grantee: Patricia Sartorelli
• Support Opportunities: Regular Research Grants