Uncovering chemical novelty from freshwater filamentous Cyanobacteria

Natural products are a valuable source of molecules with therapeutic and biotechnological applications. However, the complexity of biological matrices and the increasing rates of rediscovery pose significant challenges in the search for new bioactive compounds. Exploring novel specimens from biodiversity and utilizing modern cheminformatics tools are essential to advancing natural product discovery. In this study, we employed metabolomics and bioassays to investigate the potential of filamentous cyanobacteria collected in Brazil as a source of new bioactive secondary metabolites. Extracts and fractions from eight freshwater cyanobacterial strains were tested for their general toxicity against Artemia salina, as well as antiparasitic and cytotoxic activities and analyzed by UHPLC-HRMS-MS/MS. Molecular networks were constructed from MS/MS data using the GNPS platform, and dereplication was guided by DAFdiscovery results for feature prioritization. Annotation and dereplication were conducted using SIRIUS combined with manual analysis of HRMS and MS/MS spectra. Our study identified three cyanobacterial strains as producers of potentially novel and bioactive metabolites for in-depth investigations.