Cytotoxic potential of new caffeoyl triterpenes from the root of Acosmium diffusissimum (Mohlenbr.) Yakovlev: an in vitro and in silico approach

Two new caffeoyl triterpenes, cis-lupacosmeol (1) alone and in mixture with trans-lupacosmeol (2), and two known compounds, 16β-hydroxy-3β-trans-caffeoyl-olean-12-ene (3) and 16β-hydroxy-3β-p-coumaroyl-lup-20(29)-ene (4), were isolated from the roots of Acosmium diffusissimum. The structures were chemically characterised using 1D and 2D NMR, IR spectroscopy, and HRESIMS techniques. Cytotoxicity was evaluated against three different cancer cell lines (MCF-7, HCT-116, SK-MEL-28). Only mixture 2 showed activity against all strains tested, with more pronounced ability to inhibit SK-MEL-28 growth (IC₅₀: 25.45 µg/mL). Molecular docking studies suggested that the cytotoxic activity of 2 was strongly attributed to interactions between cis-lupacosmeol and trans-lupacosmeol, which are present in mixtures used to treat melanoma and exhibit activities towards different molecular targets of importance.