Cytotoxic Bufadienolides From The Leaves Of Melianthus Major

Melianthus major is a medicinal plant endemic to South Africa. Its leaf extract led to the isolation of five new bufadienolides, 2 beta-acetoxy-3,5-di-O-acetylhellebrigenin (1), 2 beta-acetoxy-3-O-acetylhellebrigenin (2), 2 beta-acetoxy-14-deoxy-15 beta,16 beta-epoxymelianthugenin (4), 2 beta-acet oxy-14-deoxy-15 beta,16 beta-epoxymelianthusigenin (5), and 2 beta-hydroxymelianthusigenin (6), and four known analogues. The structures of the compounds were elucidated using NMR and HRESIMS data analyses. The relative configurations were defined by single-crystal X-ray crystallography and NOESY correlations. The isolated compounds exhibited strong cytotoxicity against MCF-7 breast cancer cells and sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. Compound 1 showed the most potent activity, with IC50 values of 0.1 mu M toward CCRF-CEM and CEM/ADR5000 and 0.3 mu M toward MCF-7.