Discovery of Scalarane Sesterterpenoids From the Mollusk <i>Glossodoris hikuerensis</i> 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 (IC₅₀) 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 IC₅₀ 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.