Sesquiterpene Monomers and Dimers From the Flower of <i>Inula japonica</i> Thunb. With Selective Antiproliferation Against Breast Cancer Cells

A total of 34 sesquiterpene derivates were obtained from the flower of Inula japonica Thunb. Compounds 2, 14-34 were identified as sesquiterpene monomers, whereas the other 12 isolates (1, 3-13) were characterized as sesquiterpene dimers. Among them, japonicone Z (1), a present undescribed sesquiterpene dimer, and another undescribed monomer, japonicol A (2), were discovered. Their structures were determined through extensive spectroscopic techniques. Structurally, these dimers shared a common guaiane moiety that fused with either 1,10-seco-eudesmanes or germacrenes by a [4 + 2] biogenetic pathway. The antiproliferative activity of these isolates was assayed on triple negative breast cancer cell line (MDA-MB-231), breast cancer cell line (MCF-7), and normal human mammary epithelial cells (MCF-10A). As a result, most of these compounds exhibited significant effects toward cancer cell lines. More importantly, they possessed promising selectivity toward TNBC cell line with a dramatically increased selectivity index, as they showed similar or superior IC₅₀ values compared to paclitaxel and exhibited minimal or weak inhibitory effects on normal cells. These findings provided valuable insight for natural anti-TNBC sources.