Miliusins; Cytotoxic Neolignans From the Leaves of Miliusa Sessilis

Eight undescribed neolignans and an undescribed propanoid dimer were isolated from the leaves of Miliusa sessilis, together with two known compounds, dehydrodieugenol A and dehydrodieugenol B. All structures were elucidated by extensive spectroscopic data analysis and the structure of (7S,8R)-5'-hydroxy-3,4-dimethoxy-4',7-epoxy-8,3'-neolign-8'-en-9-acetate (miliusin A) was further confirmed by X-ray crystallographic analysis. The absolute configurations were determined using circular dichroism (CD) data analysis and the modified Mosher's method. All isolated compounds were evaluated for their cytotoxic activities against four human cancer cell lines (HeLa, HN22, HepG2, and HCT116), including one normal-type cell line (HaCaT) using MTT assay. (7S,8R)-5'-hydroxy-3,4-dimethoxy-4',7-epoxy-8,3'-neolign-8'-en-9-ol (miliusin B) was found to exhibit the most promising cytotoxic effect against Hela cells with the lowest IC₅₀ value of 0.04 μM and the highest selective index of 187.8, highlighting miliusin B as an attractive candidate for cervical cancer drug development.

Keywords: 7,8-Dihydro[b]benzofurans; 8-O-4′ neolignans; Annonaceae; Cytotoxicity; Isolation; Miliusa sessilis; Miliusins A-F.