Abstract
In this study, four previously undescribed flavonoids, named epimesatines P (1), Q (2), R (3), and S (4), were isolated from the aerial parts of Epimedium sagittatum Maxim. Their structures and absolute configurations were confirmed via spectroscopic analyses, quantum chemical electronic circular dichroism (ECD) calculations, Mo2(OAc)4-induced ECD, and Rh2(OCOCF3)4-induced ECD experiments. Epimesatines Q and R were characterized by the presence of furan rings. A cytotoxicity assay demonstrated that epimesatines P-S exhibited significant inhibitory effects on the viability of MCF-7 human breast cancer cells, with IC50 values ranging from 1.27 to 50.3 μM. Notably, epimesatines Q and R exhibited superior efficacy against MCF-7 cells compared to epimesatines P and S, suggesting that the presence of furan rings may enhance their activity against MCF-7 cells. Specifically, epimesatine Q displayed a more potent inhibitory effect at 1.27 μM compared to a positive control, docetaxel, which had an IC50 of 2.13 μM, highlighting its potential as a therapeutic agent for breast cancer. Importantly, none of the tested compounds exhibited obvious toxicity toward MCF-10A human breast epithelial cells. Furthermore, compounds 1, 3, and 4 were found to significantly inhibit the expression of sphingosine kinase 1 (Sphk1) in MCF-7 cells.