Semisynthesis and Non-Small-Cell Lung Cancer Cytotoxicity Evaluation of Germacrane-Type Sesquiterpene Lactones from <i>Elephantopus scaber</i>.
Ren H, Zhang YY, Li YL, Bai M, Yan QL, Huang XX, Cui W, Zhao H, Gu L, Liu Q, Yao GD, Song SJ.
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 <i>Elephantopus scaber</i> 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 <b>1u</b> and dimeric analog <b>3d</b> exhibited superior anti-non-small-cell lung cancer cytotoxic potencies with IC<sub>50</sub> 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 <b>1u</b> and <b>3d</b> cause G2/M phase arrest and induce apoptosis through the activation of mitochondrial pathways in A549 cells. Collectively, the results obtained suggest that compounds <b>1u</b> and <b>3d</b> are promising anti-non-small-cell lung cancer lead compounds.