Dammarane-type triterpenoids from the roots of Aglaia cucullata: mechanistic insights into the multitarget activity of shoreic acid in lung cancer

The roots of Aglaia cucullata remain poorly explored despite the reported cytotoxic potential of dammarane-type triterpenoids obtained from the species. Therefore, this study aimed to isolate dammarane-derived triterpenoids from the roots of Indonesian A. cucullata , evaluate the cytotoxic activity against A549 lung cancer cells, and investigate the potential anti-non-small cell lung cancer (anti-NSCLC) mechanism of the most active compound using network pharmacology and molecular docking. The root extract was fractionated and purified by chromatography to obtain pure compounds (1–5), whose structures were determined by HR-TOF-MS, FTIR, and NMR spectroscopy and compared with previous studies. All isolated compounds were evaluated for cytotoxicity against A549 cells using the MTT assay. Network pharmacology was used to identify potential molecular targets and signaling pathways. This was followed by molecular docking to predict binding interactions of the most active compound with selected target proteins. Furthermore, five known triterpenoids derived from the dammarane framework were isolated, namely cabralealactone (1), a C27 trisnor-dammarane γ-lactone, cabraleone (2) and ocotillone (3), dammarane-type triterpenoids, and eichlerianic acid (4), as well as shoreic acid (5), seco-dammarane derivatives. Among the isolated compounds, compound 5 represented the first report from A. cucullata and showed weak cytotoxic activity against A549 cells (IC 50 = 123.05 µM) relative to compounds 1–4. Network pharmacology identified several potential targets and signaling pathways associated with NSCLC, while molecular docking predicted favorable interactions between 5 and the selected targets. The results showed that shoreic acid (5) acted as a multitarget-modulating scaffold requiring further investigation. This study reported the roots of A. cucullata as a source of bioactive dammarane-type triterpenoids.