A novel isoflavone from Leiophyllum buxifolium (Ericaceae) and its antiproliferative effect

A new C-methyl-isoflavone, isosideroxylin 1, and a known C-methyl-flavone, sideroxylin 2, were isolated from the EtOAc extract of the leaves of Leiophyllum buxifolium. HR-ASAP-MS and 1D and 2D NMR spectroscopic data were used to determine the structure of 1. The two compounds were evaluated for their antiproliferative effects against ER^-MDA-MB-231 and ER⁺MCF-7 breast cancer cell lines and the NIH3T3 mouse fibroblast cell line with the sulforhodamine B assay. Compound 2 showed moderate antiproliferative activity on both cancer cell lines, while compound 1 displayed selective antiproliferative effect against MDA-MB-231 cells only, which supports the hypothesis of phytoestrogenic activity of 1. Neither compound was inhibitory to the NIH3T3 mouse fibroblasts at the concentrations examined. Since 1 and 2 share the A ring substitution pattern, we concluded the 5-hydroxy-7-methoxy-6,8-dimethyl substitution pattern on the A ring is responsible for the antiproliferative activity. The presence of a C-methyl-isoflavone in the Ericaceae supports the presence of a isoflavone synthesis pathway in this family.