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DOI	10.1016/j.ejmech.2021.113985
	Design, synthesis and anti-hepatocellular carcinoma activity of 3-arylisoquinoline alkaloids
	Deng, Xuemei; Luo, Tian; Li, Zhao; Wen, Huaixiu; Zhang, Honghua; Yang, Xiaoyan; Lei, Fang; Liu, Dan; Shi, Tao; Zhao, Quanyi; Wang, Zhen
通讯作者	Wang, Z (通讯作者)，Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China.
发表日期	2022
ISSN	0223-5234
EISSN	1768-3254
卷号	228
英文摘要	This article describes the syntheses and biological activity of five 3-arylisoquinoline natural products corydamine (1), N-formyl Corydamine (2), hypecumine (3), Decumbenine B (XW) and 2-(1,3-dioxolo [4,5-h]isoquinolin-7-yl)-4,5-dimethoxy-N-methyl-Benzeneethanamine (A), and twelve analogues. Among them, 1, 2, and A were synthesized for the first time. In vitro screening for anti-proliferative activity showed that derivative 1a could significantly inhibit the proliferation of HCC cells (IC50 & nbsp;=& nbsp;9.82 mM on Huh7 cells and 6.83 mM on LM9 cells), and arrest cell cycle at G(2)/M phase. The mechanistic studies further suggested compound 1a was a dual inhibitor of Topo I and Topo II, and Topo II inhibitory activity was superior to etoposide. In addition, 1a could significantly inhibit the invasion and migration of cancer cells by inhibiting the expression of MMP-9, and induce apoptosis through inhibiting the activation of the PI3K/Akt/mTOR signaling pathway. Moreover, in vivo studies demonstrated 1a could obviously reduce the growth of xenograft tumor and possessed good pharmacokinetic parameters, which indicated the potential value of 1a in treating liver cancer.& nbsp;(c) 2021 Elsevier Masson SAS. All rights reserved.
关键词	TOPOISOMERASE-I BIOLOGICAL EVALUATION ISOQUINOLINE ALKALOIDS DECUMBENINE-B DERIVATIVES CYCLIZATION INHIBITION ANTICANCER ANNULATION HYPECUMINE
英文关键词	3-Arylisoquinoline; Topoenzyme I and II dual Inhibitor
语种	英语
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:000774168800002
来源期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
来源机构	中国科学院西北生态环境资源研究院
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/254630
作者单位	[Deng, Xuemei; Luo, Tian; Li, Zhao; Zhang, Honghua; Lei, Fang; Liu, Dan; Shi, Tao; Zhao, Quanyi; Wang, Zhen] Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China; [Yang, Xiaoyan; Wang, Zhen] Univ South China, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China; [Wen, Huaixiu] Chinese Acad Sci, Northwest Inst Plateau Biol, Key Lab Tibetan Med Res, Xining 810008, Peoples R China; [Wen, Huaixiu] Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Peoples R China
推荐引用方式 GB/T 7714	Deng, Xuemei,Luo, Tian,Li, Zhao,et al. Design, synthesis and anti-hepatocellular carcinoma activity of 3-arylisoquinoline alkaloids[J]. 中国科学院西北生态环境资源研究院,2022,228.
APA	Deng, Xuemei.,Luo, Tian.,Li, Zhao.,Wen, Huaixiu.,Zhang, Honghua.,...&Wang, Zhen.(2022).Design, synthesis and anti-hepatocellular carcinoma activity of 3-arylisoquinoline alkaloids.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,228.
MLA	Deng, Xuemei,et al."Design, synthesis and anti-hepatocellular carcinoma activity of 3-arylisoquinoline alkaloids".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 228(2022).