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Structural annotation supported by spectral libraries enabled MSI level 2\u20133 annotation of 60 metabolites. Alkaloids and flavonoids were proportionally enriched in cytotoxic fractions despite the overall dominance of terpenoids. Multivariate and univariate statistical analyses demonstrated clear metabolic discrimination between active and inactive groups. Integration of VIP scores, Volcano analysis, and ROC-based prioritization identified isoquinoline and aporphine alkaloids, together with glycosylated flavonoids, as the principal contributors to cytotoxicity. The alkaloid norglaucine emerged as a key discriminant feature in the VIP\u2013Volcano intersection, consistent with its previously reported cytotoxic activity against multiple tumor cell lines. Consensus discriminant ions included\n                      <jats:italic>m\/z<\/jats:italic>\n                      330.170 and 296.12, both showing high discriminative potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study suggests a strong association between metabolomic composition and cytotoxic activity in\n                      <jats:italic>S. guianensis<\/jats:italic>\n                      , highlighting isoquinoline-derived scaffolds as promising candidates for future isolation and mechanistic investigation while demonstrating the power of metabolomics-guided strategies for natural product discovery.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11306-026-02461-1","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T13:59:55Z","timestamp":1780063195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioactivity-guided metabolomics reveals discriminant cytotoxic signatures in Siparuna guianensis"],"prefix":"10.1007","volume":"22","author":[{"given":"Salva","family":"Asghar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni B.","family":"Bevilaqua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gracimerio J.","family":"Guarneire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira C. 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