Castro_2025_Phytochemistry__114585

Eight oxindole alkaloids of the Corynanthe-type, including four previously undescribed compounds, uncamarins A-D (1-4), were isolated from the leaves of Uncaria longiflora (Por.) Merr. (Rubiaceae family) collected in the Philippines. The structures of the previously undescribed compounds were elucidated based on extensive spectroscopic data such as NMR, ECD, UV, IR, and HRESIMS, whereas known compounds were identified by comparison with published literature. Their anti-amyloidogenic activity was evaluated using a thioflavin T (ThT) fluorescence assay at 100 microg/ml. All compounds exhibited inhibitory activity, with 5 (78.44% +/- 1.63) displaying the highest % inhibition, followed by 4 (77.91% +/- 0.22) and 2 (70.40% +/- 1.93), comparable to the positive control, phenol red (82.73 +/-0.84). These results were supported by molecular docking, where compounds 2 (-7.5 kcal/mol), 4 (-7.1 kcal/mol), and 5 (-7.2 kcal/mol) exhibited strong binding affinities to the dodecameric structure of the amyloid-beta(42) protein. Notably, compound 4 also docked in silico to the active site of acetylcholinesterase, a key enzyme targeted in Alzheimer's disease (AD) therapy, thereby highlighting its potential for multitargeting in AD..