Prospecting for anticancer secondary metabolites produced by phytopathogenic fungi

Biological interactions such as phytopathogen – host represent a great source for structurally diverse bioactive secondary metabolites. Here we evaluate the antiproliferative potential of the extracts and fractions obtained by cultivation of nine different phytopathogens. The crude extract of Epicoccum sp. and Geotrichum candidum exhibited notable cytostatic effect (mean logGI50 > 0 - 1.10) against a panel of seven human cancer cell lines. Bioassay-guided fractionation of these active crude extracts was carried out using chromatographic techniques. The fractions were analyzed by (UHPLC–QTOF-MS) and screened for in vitro anticancer activity against MDA MB231 (breast), NCI-H460 (lung, non-small cells) and MCF10A (breast non-tumor cell line). Fractions JB2.2 and JB2.3 for Epicoccum sp. extract presented low and moderate anticancer activity with mean TGI values ​​of 26.4 and 15.2 µg/mL, respectively. Molecular Networking as a de-replication strategy was performed on the Global Natural Product Social Molecular Networking platform (GNPS), in order to identify secondary metabolites that could be related to the biological activity observed. We mapped the cytotoxicity profile (GI50 values) of altogether 5 fractions over the Molecular Networking searching for a link between spectral molecular networks and their anticancer activity (toxicity) (Figure 1). Thus, nodes that are uniquely present in an active fraction were priorized for further bioactivity-guided isolation studies. To the present date, only a few Epicoccum species have been studied for their bioactive secondary metabolites, which justify the necessity of an exploratory analysis regarding the anticancer activity as well as the characterization of its bioactive molecules.