Triterpenoids from the Stems of Nauclea orientalis (L.) L. (Rubiaceae)

Nauclea orientalis (L.) L. is a well-known source of varied secondary metabolites that underlie its traditional therapeutic uses and pharmacological activity. Studies on this plant in Vietnam have identified various compounds, but an investigation into the triterpenoids from its Vietnamese species and their specific biological activities has not been thoroughly conducted. This study focuses on the isolation, structural elucidation, and bioactivity evaluation of triterpenoids from the chloroform-soluble fraction of Nauclea orientalis stems. Through combined chromatographic methods, four triterpenoids (1–4) were successfully isolated. These compounds were identified as 3β,6β,23-trihydroxyolean-12-en-28-oic acid (1), rotundic acid 3,23-acetonide (2), oleanolic acid (3), and ursolic acid (4), based on spectroscopic analysis and comparison with literature data. Notably, a complete comprehensive NMR dataset, including 1H, 13C, HSQC, HMBC, and NOESY correlations, was provided for compound 1. This analysis confirmed its relative stereochemistry, resolving ambiguities present in previous literature reports. All isolated compounds were evaluated for cytotoxicity against the human breast cancer MCF-7 cell line using an MTT assay. Compound 1 exhibited the most promising moderate cytotoxicity with an IC50 value of 34.17 μM (48 h incubation), while compound 3 showed an IC50 of 87.63 μM (24 h incubation). In silico target prediction and molecular docking studies identified compound 1 as a promising hit, binding to several breast cancer-related targets (e.g., PI3K, PDGFRα). Pharmacophore modeling further suggested that the C-23 hydroxy group is a prime target for structural modification to enhance potency. These findings highlight compound 1 as a valuable scaffold for designing new cytotoxic derivatives.