Molecular Network For Accessing Polyketide Derivatives From Phomopsis Sp., An Endophytic Fungus Of Casearia Arborea (Salicaceae)

In the last three decades endophytes have shown to be a promising source for the discovery of new cytotoxic prototypes. Casearia genus shows various cytotoxic clerodane diterpenes, but the chemistry from the plant microbiota is still unknown. In this sense, the endophytic fungus Phomopsis sp. isolated from leaves of C. arborea was investigated. The EtOAc crude extract obtained from the microbial growth in rice was dereplicated using GNPS platform, based on the molecular networking obtained from UHPLC-HR-ESI-MS/MS spectral data. The used approach pointed towards different polyketide spectral families produced by the strain. Therefore, the extract was fractionated and two new derivatives, named dothiorelones P and Q, and five previously known compounds, cytosporones A and B and dothiorelones A and B, besides 15-acetoxydothiorelone A were isolated. The chemical structures were elucidated through 1D and 2D NMR and HR-ESI-MS data analysis. Additionally, cytotoxic potential of polyketide derivatives was evaluated on human cancer cells lines (A549, MCF-7, and HepG2). Dothiorelone P and cytosporone B showed low cytotoxic activity against tumor cell lines in the tested experimental conditions. However, further studies could be addressed to investigate antiproliferative and or antimetastatic potentials of these substances.