Identification, in vitro evaluation and modeling studies of the constituents from the roots of Arnebia euchroma for antitumor activity and STAT3 inhibition
Identification, in vitro evaluation and modeling studies of the constituents from the roots of Arnebia euchroma for antitumor activity and STAT3 inhibition
复制标题
紫草根成分的抗肿瘤活性和 STAT3 抑制作用的鉴定、体外评估和建模研究。
DOI：
10.1016/j.bioorg.2020.103655
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发表时间：
2020-03-01
影响因子：
5.1
通讯作者：
Shao, Meng
中科院分区：
文献类型：
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作者：
Cao, Huihui;Zhang, Wenqiang;Shao, Meng
从新疆紫草（Arnebia euchroma）的根中分离得到一个新的二聚萘醌化合物shikometabolin H（1），一个新的半萜类化合物epoxyarnebinol（5）和一个新的A-开环藿烷三萜类化合物2，3-开环二萜醇二酸（7），以及18个已知化合物。新化合物的结构经UV、IR、HRESIMS、1D和2D NMR等波谱分析确证。通过比较实验和计算的ECD数据来指定1的绝对构型，而通过比较实验和计算的OR值来实现5的绝对构型。化合物7为首次报道的A-开环藿烷型三萜化合物。MTT法结果表明，化合物1、2、4、8、11-14和19对人黑色素瘤细胞A375和A2058以及人结肠癌细胞HCT 116和SW 620具有较好的抗增殖活性。此外，还进行了分子对接研究，预测了这些活性化合物与STAT 3可能的结合模式。免疫印迹结果进一步证实了化合物1、4、8、11、14和19对STAT 3的抑制作用，这通过A2058和HCT 116细胞中磷酸化和/或总STAT 3的蛋白水平下调来指示。
Phytochemical investigation of the roots of Arnebia euchroma led to the isolation of a new dimeric naphthoquinone, shikometabolin H (1), a new meroterpeniod, epoxyarnebinol (5) and a new ring A-seco hopane triterpenoid, 2, 3-secodiplopterol dioic acid (7), together with 18 known compounds. The structures of the new compounds were elucidated by extensive spectroscopic analyses, including UV, IR, HRESIMS, 1D and 2D NMR. The absolute configuration of 1 was assigned by comparison of the experimental and calculated ECD data, whereas that of 5 was achieved by the comparison between experimental and calculated OR values. Compound 7 was found to be the first ring A-seco hopane triterpenoid ever reported. Data from MTT assays showed that compounds 1, 2, 4, 8, 11-14 and 19 possessed promising anti-proliferative activities in human melanoma cells A375 and A2058, and human colorectal adenocarcinoma cells HCT116 and SW620. In addition, molecular docking study was carried out to predict the possible binding modes of these active compounds with STAT3. Immunoblotting results further confirmed the inhibitory effects of compounds 1, 4, 8, 11, 14 and 19 on STAT3, which was indicated by the downregulated protein levels of phosphorylated and/or total STAT3 in A2058 and HCT116 cells.