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

Two new caffeoyl triterpenes, <i>cis</i>-lupacosmeol (1) alone and in mixture with <i>trans</i>-lupacosmeol (2), and two known compounds, 16β-hydroxy-3β-<i>trans</i>-caffeoyl-olean-12-ene (3) and 16β-hydroxy-3β-p-coumaroyl-lup-20(29)-ene (4), were isolated from the roots of <i>Acosmium diffusissimum</i>. 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 <i>cis</i>-lupacosmeol and <i>trans</i>-lupacosmeol, which are present in mixtures used to treat melanoma and exhibit activities towards different molecular targets of importance.