Phytochemical Investigation, Chemophenetic Significance, and Cytotoxic Activity of <em>Annona amazonica</em> (Annonaceae): Characterization of a New Aporphine Alkaloid, <em>N</em>-Formylactinodaphnine

<jats:p>Annona amazonica R.E. Fries (Annonaceae) is a tropical species native to Central and South America whose phytochemistry remains poorly explored despite its promising chemical diversity and biological potential. As part of our ongoing investigation of bioactive metabolites from Amazonian Annonaceae, the bark of A. amazonica was subjected to phytochemical investigation using classical chromatographic methods. This study led to the isolation and structural elucidation of a new N-formyl aporphine alkaloid, N-formylactinodaphnine, which occurs as an E/Z rotamer because of restricted rotation around the amide bond, together with 17 known metabolites, including diterpenes, sesquiterpenes, steroids, triterpenoids, and aporphine alkaloids. Most of these compounds are reported for the first time from A. amazonica. The cytotoxic activities of the isolated compounds were evaluated against HepG2, HCT116, MDA-MB-231, MCF-7, and U-87 MG human cancer cell lines, as well as MRC-5 noncancerous fibroblasts, using the Alamar blue assay after 72 h of incubation. Among the tested compounds, actinodaphnine exhibited the strongest cytotoxic activity, with IC50 values ranging from 5.59 to 11.73 μg/mL1 against all the tumor cell lines evaluated, whereas N-methylactinodaphnine showed the greatest activity against HCT116 cells (IC50 = 4.27 μg/mL1). These findings expand the phytochemical knowledge of A. amazonica, describe a new naturally occurring N-formyl aporphine alkaloid, and demonstrate that this Amazonian species represents a promising source of cytotoxic natural products for further pharmacological investigation.</jats:p>