Terpenylated acetophenones from the root of Ferula ferulaeoides (Steud.) Korov. with selective cytotoxic activity.

Eleven undescribed terpenylated acetophenones (1, 2a/2b, 3a/3b, 4-6, 7a/7b, 8) and twelve known analogues (9a/9b, 10-12, 13a/13b, 14a/14b, 15, 16a/16b) were isolated from the roots of Ferula ferulaeoides (Steud.) Korov. (Apiaceae) by the guidance of bioactivity-guided approach. The structures and relative configurations of the new compounds were established by extensive analysis of UV, HR-ESI-MS, and NMR data, supported by 13C NMR calculations with custom DP4+ probability analysis. Through electronic circular dichroism, the absolute configurations of all compounds were determined for the first time. Cytotoxic activities of all compounds were evaluated against HCT-116, HT-29, and HCoEpiC cell lines, and most of them (1, 4, 7-15) showed significant or moderate selective cytotoxic activity toward colon cancer cells. Among them, compound 10 showed the most potent cytotoxic effects against HCT-116 cells (IC50, 8.23 ± 2.3 μM) and HT-29 cells (IC50, 12.43 ± 2.2 μM), while showing significantly lower cytotoxicity toward normal colonic epithelial cells (IC50, 52.26 ± 2.9 μM for HCoEpiC).