西藏雪山巴豆 来源于西藏雪山巴豆中的倍半萜香豆素及其抗胰腺癌效应
Sesquiterpene coumarins from Ferula sinkiangensis and their anti-pancreatic cancer effects.
发表日期:2023 Aug 17
作者:
Jia-Lin Wang, Chun-Yan Sang, Jun Wang, Pei-Lin Li, Tian Chai, Mohammad Reza Naghavi, Ya-Min Zhao, Jun-Li Yang
来源:
BIOMASS & BIOENERGY
摘要:
已经从新疆当归(伞形科)根部分离得到了八个前所未报告的倍半萜香豆素,即(+)-和(-)-ferulasinkian A(1),(-)-fukanefuromarin M(2),(±)-ferulasinkian C(3),(±)-ferulasinkian D(4),ferulasinkian E(5),ferulasinkian F(7)和ferulasinkian G(8),以及两个已知化合物,即(+)-fukanefuromarin M(2)和7-羟基ferprenin(6)。通过光谱分析、电化学圆二色光谱计算和旋光计算,阐明了所有化合物的结构。化合物1-6为二聚物,由一条链状倍半萜和一种含氧六元环的香豆素连接,连接处位于香豆素C-3和C-4。目前,该属只有七个这样的结构报道,它们的绝对构型尚未确定。化合物7-8是一种链状倍半萜连接在香豆素C-4上的倍半萜香豆素衍生物。在本研究中,成功地对化合物(±)-1和(±)-2进行了手征分离,并确定了化合物(±)-1,(±)-2,5,7和8的绝对构型。对所分离的化合物进行了对人胰腺癌细胞系(包括CFPAC-1,PANC-1,CAPAN-2和SW 1990)的细胞毒性活性评估。化合物(+)-1,(-)-1和7对胰腺癌细胞表现出强大的细胞毒性,其IC50值在4.57±0.94到14.01±1.03μM范围内。此外,对(-)-1的初步机理研究表明,它能诱导CFPAC-1细胞凋亡。版权所有 © 2023 Elsevier Ltd.
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.Copyright © 2023. Published by Elsevier Ltd.