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黄花蒿中环烯醚萜类化合物对肝星状细胞系 LX2 的细胞毒性作用。

Cytotoxic sesquiterpenoids against hepatic stellate cell line LX2 from Artemisia lavandulaefolia.

机构信息

State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.

出版信息

Bioorg Chem. 2020 Oct;103:104107. doi: 10.1016/j.bioorg.2020.104107. Epub 2020 Jul 17.

Abstract

The preliminary assay suggested that the EtOH extract of Artemisia lavandulaefolia had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with an inhibitory ratio of 94.1% at 400 μg/mL. Bioassay-guided investigation led to eleven new sesquiterpenoids, artemilavanolides C-F (1-4) and artemlavandulolides A-G (5-11), as well as thirteen known compounds (12-24). Their structures were elucidated by extensive spectroscopic data and X-ray crystallographic analysis. Cytotoxicity evaluation suggested that fourteen compounds exhibited activity against HSC-LX2; compounds 22, 23 and 24 were comparable to the positive control, silybin (IC, 162.3 μM); compounds 6, 9 and 16 showed moderate activity with IC values of 109.3, 114.0 and 124.2 μM. Importantly, compounds 14, 15 and 18 displayed significant cytotoxicity against HSC-LX2 with IC values of 52.1, 16.5 and 21.3 μM, and inhibitory activity on the deposition of human collagen type I (Col I) and human laminin (HL) with IC values ranging from 7.3 to 71.6 μM and from 18.6 to 72.9 μM.

摘要

初步测定表明,艾蒿 EtOH 提取物对肝星状细胞系 LX2(HSC-LX2)具有细胞毒性,在 400μg/mL 时抑制率为 94.1%。基于生物测定的研究导致了 11 种新的倍半萜,即 artemilavanolides C-F(1-4)和 artemlavandulolides A-G(5-11),以及 13 种已知化合物(12-24)。通过广泛的光谱数据分析和 X 射线晶体学分析阐明了它们的结构。细胞毒性评估表明,有 14 种化合物对 HSC-LX2 具有活性;化合物 22、23 和 24 与阳性对照物水飞蓟宾(IC,162.3μM)相当;化合物 6、9 和 16 具有中等活性,IC 值分别为 109.3、114.0 和 124.2μM。重要的是,化合物 14、15 和 18 对 HSC-LX2 具有显著的细胞毒性,IC 值分别为 52.1、16.5 和 21.3μM,对人胶原蛋白 I(Col I)和人层粘连蛋白(HL)的沉积抑制活性 IC 值范围为 7.3 至 71.6μM 和 18.6 至 72.9μM。

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