Sesquiterpene Monomers and Dimers From the Flower of Inula japonica 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 IC values compared to paclitaxel and exhibited minimal or weak inhibitory effects on normal cells. These findings provided valuable insight for natural anti-TNBC sources.