Semisynthesis and Non-Small-Cell Lung Cancer Cytotoxicity Evaluation of Germacrane-Type Sesquiterpene Lactones from Elephantopus scaber

Two series of germacrane-type sesquiterpene
lactones were produced
by semisynthetic modulation of scaberol C, which was prepared by a
standard chemical transformation from an Elephantopus
scaber extract. Their inhibition activities against
non-small-cell lung cancer cells were screened, and preliminary structure–activity
relationships were also established. Among them, monomeric analog 1u and dimeric analog 3d exhibited superior anti-non-small-cell
lung cancer cytotoxic potencies with IC50 values of 4.3
and 0.7 μM against A549 cells, respectively, and were more active
than cisplatin and the standard sesquiterpene lactones, parthenolide
and scabertopin. Further studies revealed that compounds 1u and 3d cause G2/M phase arrest and induce apoptosis
through the activation of mitochondrial pathways in A549 cells. Collectively,
the results obtained suggest that compounds 1u and 3d are promising anti-non-small-cell lung cancer lead compounds.