Diverse Sesquiterpenoids From the Aerial Parts of Inula japonica Thunb. and Their Cytotoxic Activities

ABSTRACT 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 IC 50 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 IC 50 values ranging from 18.21 ± 0.94 to 36.54 ± 0.80 µM.