Sesquiterpene coumarins from Ferula sinkiangensis and their anti-pancreatic cancer effects

Eight previously unreported sesquiterpene coumarins, namely (+)- and (-)-ferulasinkian A (1), (-)-fukanefuromarin M (2), (±)-ferulasinkian C (3), (±)-ferulasinkian D (4), ferulasinkian E (5), ferulasinkian F (7), and ferulasinkian G (8), together with two known compounds, (+)-fukanefuromarin M (2) and 7-hydroxyferprenin (6), have been isolated from the roots of Ferula sinkiangensis (Umbelliferae). The structures of all compounds were elucidated by spectroscopic analysis, along with ECD calculations and optical rotation calculations. Compounds 1-6 are dimers consisting of a chain sesquiterpene and a coumarin with an oxygen-containing six-membered ring connected from coumarin C-3 and C-4. Currently, there are only seven such structures reported in the genus Ferula, and their absolute configurations have not yet been determined. Compounds 7-8 are sesquiterpene coumarin derivatives with a chain sesquiterpene connected with coumarin C-4. In the present study, the chiral separation of compounds (±)-1 and (±)-2 was successfully carried out, and the absolute configurations of compounds (±)-1, (±)-2, 5, 7 and 8 were determined. The isolates were evaluated for their cytotoxic activity against human pancreatic cancer cell lines including CFPAC-1, PANC-1, CAPAN-2 and SW 1990. Compounds (+)-1, (-)-1 and 7 exhibited potent cytotoxicity against pancreatic cancer cells with IC₅₀ values ranging from 4.57 ± 0.94 to 14.01 ± 1.03 μM. Furthermore, the primary mechanistic study of (-)-1 demonstrated that it could induce apoptosis in CFPAC-1 cells.