Discovery of Scalarane Sesterterpenoids From the Mollusk Glossodoris hikuerensis Exhibiting Anticancer Effects Against Drug‐resistant Lung Cancer Cells

A new scalarane‐type sesterterpene ( 1 ), along with four known related compounds ( 2 – 5 ), was isolated from the nudibranch mollusk Glossodoris hikuerensis . Compound 6 was also obtained from 4 by chemical conversion. Their structures were established by extensive spectroscopic analysis, chemical conversion, and by the comparison of their spectroscopic data with those reported in the literature. In bioassay, compound 1 inhibited the proliferation of human leukemia U937 cells with a half‐maximal inhibitory concentration (IC 50 ) value of 7.1 µM. Compounds 2 , 3 , and 6 exhibited inhibitory activities against a variety of human cancer cell lines, including U937, K562, A549, HCC827, and gefitinib‐resistant HCC827 cells, with IC 50 values 0.7−10.1 µM. Furthermore, compound 6 significantly induced apoptosis, reduced mitochondrial membrane potential, and suppressed cellular invasion and migration by inhibiting EGFR/PI3K signaling pathway.