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Isolation, synthesis and bioactivity evaluation of isoquinoline alkaloids from Corydalis hendersonii Hemsl. against gastric cancer in vitro and in vivo | |
Luo, T; Li, Z; Deng, XM; Jiang, K; Liu, D; Zhang, HH; Shi, T; Liu, LY; Wen, HX; Li, QE; Wang, Z | |
2022 | |
发表期刊 | BIOORGANIC & MEDICINAL CHEMISTRY |
卷号 | 60 |
摘要 | Isoquinoline alkaloid displays significant anti-gastric cancer effects due to its unique structure, which is attracting more and more attention for the development of anti-gastric cancer drugs. In this study, we explore the active components against gastric cancer from the Tibetan Medicine Corydalis hendersonii Hemsl, which is rich in isoquinoline alkaloids. 14 compounds including 2 previously undescribed natural products were obtained. Interestingly, an new active compound displays potent anti-gastric cancer activity. After accomplishing the total syntheses of the active compound and its derivatives, the anti-gastric cancer activity of the active compound was further investigated. In vitro experiments revealed that the active compound significantly attenuated the proliferative capacity, caused G2/M phase arrest, inhibited the cell migration and invasion, and induced cell apoptosis. Mechanistically, the active compound could increase the Bax/Bcl-2 ratio, elevate cytochrome c in the cytosol, and activate caspase-9/3, along with inactivating the upstream PI3K/Akt/mTOR signaling pathway. In addition, the active compound could also cause gastric cancer cell death by inhibiting topoisomerase I activity. More importantly, the anti-gastric cancer activity of the active compound was confirmed in MGC-803 xenograft nude mice in vivo. This work not only promotes the exploitation of Corydalis hendersonii Hemsl., but also provides some experience for discovering new entities from natural sources. |
收录类别 | SCIE |
文献类型 | 期刊论文 |
条目标识符 | http://210.75.249.4/handle/363003/61236 |
专题 | 中国科学院西北高原生物研究所 |
推荐引用方式 GB/T 7714 | Luo, T,Li, Z,Deng, XM,et al. Isolation, synthesis and bioactivity evaluation of isoquinoline alkaloids from Corydalis hendersonii Hemsl. against gastric cancer in vitro and in vivo[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2022,60. |
APA | Luo, T.,Li, Z.,Deng, XM.,Jiang, K.,Liu, D.,...&Wang, Z.(2022).Isolation, synthesis and bioactivity evaluation of isoquinoline alkaloids from Corydalis hendersonii Hemsl. against gastric cancer in vitro and in vivo.BIOORGANIC & MEDICINAL CHEMISTRY,60. |
MLA | Luo, T,et al."Isolation, synthesis and bioactivity evaluation of isoquinoline alkaloids from Corydalis hendersonii Hemsl. against gastric cancer in vitro and in vivo".BIOORGANIC & MEDICINAL CHEMISTRY 60(2022). |
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