Design and Synthesis of Cytotoxic Water-Soluble Rocaglaol Derivatives against HEL Cells by Inhibiting Fli-1

doi:10.1021/acs.jnatprod.3c00948

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	Design and Synthesis of Cytotoxic Water-Soluble Rocaglaol Derivatives against HEL Cells by Inhibiting Fli-1
	Ge, Wei; Ming, Weikang; Li, Zhenkun; Tang, Yunyan; Li, Ya-Nan; Yang, Jue; Hao, Xiaojiang; Yuan, Chunmao
	2024
发表期刊	JOURNAL OF NATURAL PRODUCTS
ISSN	0163-3864
页码	-
摘要	Rocaglaol, embedding a cyclopenta[b]benzofuran scaffold, was isolated mainly from the plants of Aglaia and exhibited nanomolar level antitumor activity. However, the drug-like properties of these compounds are poor. To improve the physicochemical properties of rocaglaol, 36 nitrogen-containing phenyl-substituted rocaglaol derivatives were designed and synthesized. These derivatives were tested for the inhibitory effects on three tumor cell lines, HEL, MDA-231, and SW480, using the MTT assay. Among them, 22 derivatives exhibited good cytotoxic activities with IC50 values between 0.11 +/- 0.07 and 0.88 +/- 0.02 mu M. Fourteen derivatives exhibited stronger cytotoxicity than the positive control, adriamycin. In particular, a water-soluble derivative revealed selective cytotoxic effects on HEL cells (IC50 = 0.19 +/- 0.01 mu M). This compound could induce G1 cell cycle arrest and apoptosis in HEL cells. Western blot assays suggested that the water-soluble derivative could downregulate the expression of the marker proteins of apoptosis, PARP, caspase-3, and caspase-9, thus inducing apoptosis. Further CETSA and Western blot studies implied that this water-soluble derivative might be an inhibitor of friend leukemia integration 1 (Fli-1). This water-soluble derivative may serve as a potential antileukemia agent by suppressing the expression of Fli-1.
DOI	10.1021/acs.jnatprod.3c00948
WOS记录号	WOS:001162285700001
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/76016
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Ge, Wei,Ming, Weikang,Li, Zhenkun,et al. Design and Synthesis of Cytotoxic Water-Soluble Rocaglaol Derivatives against HEL Cells by Inhibiting Fli-1[J]. JOURNAL OF NATURAL PRODUCTS,2024:-.
APA	Ge, Wei.,Ming, Weikang.,Li, Zhenkun.,Tang, Yunyan.,Li, Ya-Nan.,...&Yuan, Chunmao.(2024).Design and Synthesis of Cytotoxic Water-Soluble Rocaglaol Derivatives against HEL Cells by Inhibiting Fli-1.JOURNAL OF NATURAL PRODUCTS,-.
MLA	Ge, Wei,et al."Design and Synthesis of Cytotoxic Water-Soluble Rocaglaol Derivatives against HEL Cells by Inhibiting Fli-1".JOURNAL OF NATURAL PRODUCTS (2024):-.

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