Four undescribed sappanin-type homoisoflavanones isolated from Polygonatum odoratum with anti-tumor effects and molecular docking study.

Four previously undescribed sappanin-type homoisoflavanones (1-4) and eighteen known compounds (5-22) were isolated from Polygonatum odoratum (Mill.) Druce rhizomes. The structures and absolute configurations were established through extensive spectroscopic analyses, including NMR, HRESIMS, and theoretical ECD calculations. Cytotoxicity against four human cancer cell lines (A549, MDA-MB-231, HGC-27, and HCT-15) was assessed using the CCK-8 assay. Molecular docking with thymidylate synthase (TS) enzyme was performed to analyze the mechanism. Compound 16 exhibited higher cytotoxicity against HCT-15 cells than 5-FU (IC50 = 27.25 ± 1.84 vs 36.36 ± 4.87 μM). Compounds 6 and 16 also showed significant inhibition of HGC-27 cells (IC50 values of 28.72 ± 4.69 and 10.19 ± 1.90 μM, respectively). Docking revealed key interactions between compounds 6 and 16 and the TS enzyme.