Efficient synthesis of new phenanthridine Wnt/beta-catenin signaling pathway agonists

doi:10.1016/j.ejmech.2018.08.064

	Efficient synthesis of new phenanthridine Wnt/beta-catenin signaling pathway agonists
	Chen, Duozhi 1; Zhang, Heng 2,3; Jing, Chenxu 4; He, Xiaoli 2; Yang, Bijuan 1; Cai, Jieyun 1; Zhou, Yunfu 2; Song, Xiaoming 2; Li, Lin 2; Hao, Xiaojiang1
	2018-09-05
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN	0223-5234
卷号	157 页码:1491-1499
摘要	Previously, HLY78, a lycorine derivative, was identified as the first Wnt/beta-catenin signaling agonist through binding to the DAX domain of Axin, a scaffold of Wnt/beta-catenin complex. In this study, to obtain more potent Wnt/beta-catenin agonist, the structure optimization of HLY78 was carried out by design and synthesis of six phenanthridine derivatives, which afforded five active ones. In particular, 8,9-bis((1,3-dimethyl-1H-pyrazol)methoxy)-5-ethyl-4-methyl-5,6-dihydrophenanthridine showed the most potent activity (0.15/mu M) that was increased nearly 30 times as that of the lead HLY78. These compounds may be valuable in future pharmacological or biological studies. (C) 2018 Elsevier Masson SAS. All rights reserved.
关键词	Wnt/beta-catenin signaling agonist Phenanthridine derivatives Structural optimization
DOI	10.1016/j.ejmech.2018.08.064
语种	英语
WOS记录号	WOS:000447480000104
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/62781
专题	植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Li, Lin; Hao, Xiaojiang
作者单位	1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol,Innovat Ctr Cell Signali, State Key Lab Mol Biol,CAS Ctr Excellence Mol Cel, Shanghai 200031, Peoples R China 3.Univ Chinese Acad Sci, Shanghai, Peoples R China 4.Changchun Univ Chinese Med, Affiliated Hosp, Res Ctr Tradit Chinese Med, Changchun 130021, Peoples R China
推荐引用方式 GB/T 7714	Chen, Duozhi,Zhang, Heng,Jing, Chenxu,et al. Efficient synthesis of new phenanthridine Wnt/beta-catenin signaling pathway agonists[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,157:1491-1499.
APA	Chen, Duozhi.,Zhang, Heng.,Jing, Chenxu.,He, Xiaoli.,Yang, Bijuan.,...&Hao, Xiaojiang.(2018).Efficient synthesis of new phenanthridine Wnt/beta-catenin signaling pathway agonists.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,157,1491-1499.
MLA	Chen, Duozhi,et al."Efficient synthesis of new phenanthridine Wnt/beta-catenin signaling pathway agonists".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 157(2018):1491-1499.