Diverse Sesquiterpenoids From the Aerial Parts of <i>Inula japonica</i> Thunb. and Their Cytotoxic Activities

Three previously undescribed sesquiterpenoids, named inujaponins J-L (1, 3, and 4), were isolated from the aerial parts of Inula japonica Thunb., together with nine known sesquiterpenoids (2 and 5-12). The structures of the new sesquiterpenoids were characterized using high-resolution mass spectrometry and comprehensive one-dimensional and two-dimensional nuclear magnetic resonance (NMR) analyses. Additionally, the absolute configurations of 1, 3, and 4 were determined by comparing the experimental and calculated electronic circular dichroism spectra. Furthermore, the carbon-13 NMR data for 5 and 6 are reported for the first time in the present study. Structurally, inujaponin J was a rare presilphiperfolane sesquiterpenoid possessing a 5/5/6 tricyclic system, inujaponin K was an ivaxillarane sesquiterpenoid containing a 3/5/6 tricycle carbon skeleton, and inujaponin L was an eremophilane sesquiterpenoid possessing an α-substituted acrylic acid unit. Compounds 6, 7, and 12 had remarkable cytotoxic activities against K-562, A-549, HepG-2, MDA-MB-231, and SW-480 cancer cell lines with IC₅₀ values ranging from 13.41 ± 0.25 and 29.36 ± 0.36 µM. Compounds 8, 9, and 11 showed selective inhibitory activities against five cancer cell lines, with IC₅₀ values ranging from 18.21 ± 0.94 to 36.54 ± 0.80 µM.