Two new dammarane-type triterpenoids and other constituents from <i>Gymnosporia diversifolia</i> with anti-inflammatory and cytotoxic activities

Eighteen compounds were afforded from the aerial parts of <i>Gymnosporia diversifolia</i> collected in Vietnam. These included two new dammarane-type triterpenoids, gymnosporones A-B (1-2), fourteen previously identified triterpenoids (3-16), and two phenolic compounds (17-18). The structures of new components were elucidated by a combination of IR, HRESIMS, 1D-, 2D-NMR spectroscopic methods as well as by comparison with previously reported data. Compounds 3, 7, and 8 demonstrated inhibitory activity against NO production in RAW 264.7 macrophage cells, with IC₅₀ values ranging from 71.85 to 95.71 μM. In cytotoxicity assays, compounds 1-3, 7, 8, 11, 15 and 16 exhibited moderate activity against A549, Hep-G2, and MCF-7 human cancer cell lines, with IC₅₀ values between 10.65 and 47.78 μM. Among these, compound 15 was the most active, showing IC₅₀ values of 10.65-14.28 μM across all tested cancer cell lines. <i>In silico</i> studies demonstrated that compounds 7 (-9.7 kcal mol^-1) and 11 (-9.4 kcal mol^-1) exhibited the strongest binding affinities for tubulin, whereas compound 15 showed strong dual binding to both tubulin (-8.7 kcal mol^-1) and BCL-2 (-9.1 kcal mol^-1). Molecular dynamics simulations confirmed the stability of ligand 15-protein complexes and revealed a more favorable binding free energy for tubulin (-28.59 <i>vs.</i> -24.04 kcal mol^-1). Together with the <i>in vitro</i> results, these findings support a dual-target mechanism in which compound 15 may exert anticancer effects by inhibiting microtubule polymerization and inducing apoptosis. Our results highlight <i>G. diversifolia</i> as a rich source of structurally diverse triterpenoids with significant anticancer potential.