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

Jia-Lin Wang; Chun-Yan Sang; Jun Wang; Pei-Lin Li; Tian Chai; Mohammad Reza Naghavi; Ya-Min Zhao; Jun-Li Yang

doi:10.1016/j.phytochem.2023.113824

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

Phytochemistry. 2023 Oct:214:113824. doi: 10.1016/j.phytochem.2023.113824. Epub 2023 Aug 18.

Authors

Jia-Lin Wang¹, Chun-Yan Sang², Jun Wang³, Pei-Lin Li², Tian Chai², Mohammad Reza Naghavi⁴, Ya-Min Zhao⁵, Jun-Li Yang⁶

Affiliations

¹ College of Chemical Engineering, Experimental Teaching Department, Northwest Minzu University, Key Laboratory of Environment-Friendly Composite Materials of the State Ethnic Affairs Commission, Gansu Provincial Biomass Function Composites Engineering Research Center, Key Laboratory for Utility of Environment-Friendly Composite Materials and Biomass in University of Gansu Province, Lanzhou 730030, China.
² CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou, 730000, People's Republic of China.
³ Shandong Laboratory of Yantai Advanced Materials and Green Manufacturing, Yantai 264006, China; Yantai Zhongke Research Institute of Advanced Materials and Green Chemical Engineering, Yantai 264010, PR China.
⁴ Agricultural & Natural Resources College, University of Tehran, Karaj, Iran.
⁵ College of Chemical Engineering, Experimental Teaching Department, Northwest Minzu University, Key Laboratory of Environment-Friendly Composite Materials of the State Ethnic Affairs Commission, Gansu Provincial Biomass Function Composites Engineering Research Center, Key Laboratory for Utility of Environment-Friendly Composite Materials and Biomass in University of Gansu Province, Lanzhou 730030, China. Electronic address: 1203481731@qq.com.
⁶ CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou, 730000, People's Republic of China. Electronic address: yangjl@licp.cas.cn.

PMID: 37597719
DOI: 10.1016/j.phytochem.2023.113824

Abstract

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.

Keywords: Ferula sinkiangensis; Pancreatic cancer; Sesquiterpene coumarins; Umbelliferae.