Cytotoxic, antibacterial, and aromatase inhibitory activities of cycloartane triterpenes and flavones from Gardenia obtusifolia

Ten previously undescribed cycloartane-type triterpenes (1-10) and nineteen known compounds (11-29), including flavones, were isolated from Gardenia obtusifolia, a plant belonging to the family Rubiaceae. Their structures were elucidated using a combination of spectroscopic techniques, including 1D and 2D NMR and HRESIMS, while their absolute configurations were determined through single-crystal X-ray diffraction analysis and ECD calculations. Among the isolates, compound 2 featured a δ-lactone moiety as the D-ring, representing the first report of such a structural novelty in cycloartane triterpenoids. Biological evaluations revealed that most isolated cycloartane triterpenoids exhibited moderate to weak cytotoxicity, while the flavones showed stronger cytotoxic effects. Notably, flavone 27 exhibited potent cytotoxicity against the A549, MOLT-3, and HepG2 cell lines (IC₅₀: 0.4-1.0 μM), and flavone 25 was selectively efficacious against the A549 cell line (IC₅₀: 0.5 μM). Antibacterial assays indicated that cycloartane triterpenoids 4, 13, 16, and 18 exhibited activity against Staphylococcus aureus and Bacillus cereus, with compound 18 showing the strongest inhibition. In addition, the seco-cycloartane derivatives 13 and 16 were identified as effective inhibitors of aromatase activity.