Title: Metabolômica de fungos endofíticos associados à Baccharis oxyodonta DC.(Asteraceae): da quimiodiversidade à citotoxicidade
Abstract: Microorganisms represent a spectacular source of bioactive metabolites and they may have applications such as pesticides, antibiotics, immunosuppressants, antiparasitics, antitumor, among others.Endophytic fungi are a rich source of bioactive compounds, especially cytotoxic components.The objective of this work was to contribute to the knowledge about the chemical and biological diversity of endophytic fungi from male and female Baccharis oxyodonta DC. (Asteraceae).Thereby, the endophytic fungi of male and female individuals from B. oxyodonta were isolated and identified by sequencing of ITS region and using phylogenetic tree construction.Twenty-eight fungi belonging to the Alternaria, Annulohypoxylon, Cercospora, Colletotrichum, Phomopsis and Preusia genera, and the families Dydimellaceae and Strophariaceae were isolated from females.From the male, 20 fungi distributed among the genera Alternaria, Aspergillus, Cladosporium, Penicillium, Periconia and Phomopsis were obtained.Strains were cultivated using three different media (rice, BDA and Czapek).After extraction procedures, the resulting 136 samples were analyzed by HPLC/MS-MS and a metabolomic approach was performed to allow the visualization of the impact of different culture conditions on the metabolic profile of strains.From this analysis could be verified that BDA medium furnished the highest metabolic diversity and were identified different classes of compounds such as anthraquinones, xanthones, amides, sesquiterpene lactones, fatty acids, isocoumarins, diketopiperazines and polyketides.The extracts were evaluated for cytotoxic potential using the MTT assay.Eleven extracts tested at a concentration of 50 µg.mL - were considered active against the HCT-116 tumor cell line (colorectal carcinoma).Based on the cytotoxicity and metabolic profile results, two strains, Alternaria sp. 1 and Phomopsis sp. 4, were selected for large-scale cultivation.After chromatographic procedures and spectral analysis of the isolated compounds, four components from Alternaria sp. 1 were identified as alternariol, alternariol methylether, altenusine and 5'-methoxy-6-methyl-biphenyl-3,4,3'-triol and from the crude extract of Phomopsis sp. 4 were identified sydowinin B, 8-hydroxy-6-methyl-xanthone carboxylic acid, unpublished in the genus, and a new compound phomopsixanthone.Isolated compounds were evaluated for cytotoxicity, however only alternariol showed moderate inhibition activity against the HCT-116 tumor cell line.