Synthesis and anti-fibrotic effects of santamarin derivatives as cytotoxic agents against hepatic stellate cell line LX2

doi:10.1016/j.bmcl.2021.127994

KIB OpenIR

	Synthesis and anti-fibrotic effects of santamarin derivatives as cytotoxic agents against hepatic stellate cell line LX2
	Wang,Jin-Ping ; Li,Tian-Ze ; Huang,Xiao-Yan ; Geng,Chang-An ; Shen,Cheng ; Sun,Jin-Jin ; Xue,Dong ; Chen,Ji-Jun
	2021
发表期刊	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN	0960-894X
卷号	41 页码:127994
摘要	Liver fibrosis is a final result of extensive deposition of extracellular matrix (ECM) and starts with the activation and proliferation of hepatic stellate cells (HSCs). Our previous study showed that eudesmane sesquiterpenoid santamarin had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values of 16.5 ? 0.7 ?M. To explore the structure?activity relationships, twenty-six derivatives were synthesized by modifying the hydroxyl group, double-bond and unsaturated lactone. Cytotoxicity evaluation suggested that eight derivatives (6, 9, 13, 17, 20 and 25?27) increased activity against HSC-LX2. Especially, derivatives 17, 20 and 25 displayed obvious cytotoxicity with IC50 values of 6.4 ? 0.4, 4.6 ? 0.1, and 3.5 ? 0.1 ?M, which were 3 to 5-fold higher than santamarin. Preliminary mechanisms study revealed that the active compound 20 exhibited more than 8fold and 6-fold enhancement of inhibitory effect on the deposition of human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 7.6 ? 0.6 and 3.3 ? 1.2 ?M.
关键词	Santamarin derivatives Anti-fibrotic effects HSC-LX2 Extracellular matrix NF-KAPPA-B SESQUITERPENE LACTONES LIVER FIBROSIS STRUCTURE REQUIREMENT BAY LEAF ACTIVATION
DOI	10.1016/j.bmcl.2021.127994
WOS记录号	WOS:000651228800011
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/73168
专题	中国科学院昆明植物研究所
作者单位	1.[Wang, Jin-Ping 2.Li, Tian-Ze 3.Huang, Xiao-Yan 4.Geng, Chang-An 5.Shen, Cheng 6.Sun, Jin-Jin 7.Chinese Acad Sci, Kunming Inst Bot, Yunnan Key Lab Nat Med Chem, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 8.Shaanxi Normal Univ, Minist Educ, Key Lab Appl Surface & Colloid Chem, Xian 710062, Peoples R China 9.Shaanxi Normal Univ, Sch Chem & Chem Engn, Xian 710062, Peoples R China 10.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Wang,Jin-Ping,Li,Tian-Ze,Huang,Xiao-Yan,et al. Synthesis and anti-fibrotic effects of santamarin derivatives as cytotoxic agents against hepatic stellate cell line LX2[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2021,41:127994.
APA	Wang,Jin-Ping.,Li,Tian-Ze.,Huang,Xiao-Yan.,Geng,Chang-An.,Shen,Cheng.,...&Chen,Ji-Jun.(2021).Synthesis and anti-fibrotic effects of santamarin derivatives as cytotoxic agents against hepatic stellate cell line LX2.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,41,127994.
MLA	Wang,Jin-Ping,et al."Synthesis and anti-fibrotic effects of santamarin derivatives as cytotoxic agents against hepatic stellate cell line LX2".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 41(2021):127994.

条目包含的文件		下载所有文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
156-I18-020-2021-王金平（567KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	浏览下载