Integrating cytotoxicity and NMR-based metabolomics to uncover bioactive aporphine alkaloids and pentacyclic triterpenoids from Siparuna guianensis.

Siparuna guianensis is a medicinal species widely used in South America, although its cytotoxic constituents remain poorly characterised. In this study, the hydroethanolic leaf extract and solvent-partitioned fractions (hexane, ethyl acetate, butanol, aqueous and alkaloid fraction) were evaluated against MCF-7, 4T1, and MDA-MB-231 breast cancer cell lines and subsequently investigated by NMR-based metabolomics. The crude extract, hexane, and ethyl acetate fractions exhibited the strongest cytotoxic effects, whereas the butanol, alkaloid and aqueous fractions showed little or no activity. NMR-guided dereplication suggested the occurrence of aporphine and oxoaporphine alkaloids, including glaucine-, norglaucine-, isocorydine-, N-methyllaurotetanine-, oxoglaucine-, liriodenine-, and dehydroglaucine-related compounds. Pentacyclic triterpenoids tentatively annotated included lupeol-, taraxerol-, taraxasterol-, pseudotaraxasterol-, ursane-, and oleanane-type derivatives. The enrichment of these relatively apolar metabolites in the active fractions suggests a direct association with the observed antitumoral effects through chemometric analysis. These findings highlight S. guianensis as a promising source of cytotoxic natural products for anticancer research.