Design, synthesis and biological evaluation of esculetin derivatives as anti-tumour agents

	Design, synthesis and biological evaluation of esculetin derivatives as anti-tumour agents
	Wang, Ping; Xia, Yang-Liu; Yu, Yang; Lu, Jun-Xia; Zou, Li-Wei; Feng, Lei; Ge, Guang-Bo; Yang, Ling
刊名	rsc advances
	2015
卷号	5 期号:66 页码:53477-53483
英文摘要	esculetin, a naturally catecholic coumarin, possess multiple pharmacological activities including antitumour, anti-inflammatory and anti-oxidant. however, the extensive phase ii metabolism and rapid elimination from the human body significantly hinder esculetin and its derivatives as drug leads/candidates. to improve both the metabolic stability and the anti-tumour activity of esculetin via rational modification, a series of c-4 and c-8 substituted derivatives were designed and synthesized by perchloric acid catalysed von pechmann reaction and mannich reaction, respectively. the in vitro metabolic half-life in human liver s9 and anti-tumour activities in a549 and b16 cell lines of the newly synthesized compounds were assayed. of these compounds, 8-(pyrrolidin-1-ylmethyl)-4-trifluoromethyl esculetin 15 was the most potent candidate compound, with almost a 20-fold increase in antiproliferative activity and a 3-fold prolonged half-life in human liver s9 compared with the parent compound 1. in addition, the potential structure-activity relationship and structure-metabolic stability relationship were discussed. notably, the introduction of a nitrogen containing group as a hydrogen bond acceptor at the c-8 position of esculetin can improve both the metabolic stability and anti-tumour activity. all of these findings are very helpful for the structural modification of esculetin and other bioactive phenolic compounds to improve their phase ii metabolic stability and bioactivity synchronously.
WOS标题词	science & technology ; physical sciences
类目[WOS]	chemistry, multidisciplinary
研究领域[WOS]	chemistry
关键词[WOS]	leukemia u937 cells ; lipoxygenase inhibitor ; simple coumarins ; apoptosis ; series ; hydroxycoumarins ; glucuronidation ; induction ; lines
收录类别	SCI
语种	英语
WOS记录号	WOS:000356801300040
公开日期	2016-05-09
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/146347]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
作者单位	Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
推荐引用方式 GB/T 7714	Wang, Ping,Xia, Yang-Liu,Yu, Yang,et al. Design, synthesis and biological evaluation of esculetin derivatives as anti-tumour agents[J]. rsc advances,2015,5(66):53477-53483.
APA	Wang, Ping.,Xia, Yang-Liu.,Yu, Yang.,Lu, Jun-Xia.,Zou, Li-Wei.,...&Yang, Ling.(2015).Design, synthesis and biological evaluation of esculetin derivatives as anti-tumour agents.rsc advances,5(66),53477-53483.
MLA	Wang, Ping,et al."Design, synthesis and biological evaluation of esculetin derivatives as anti-tumour agents".rsc advances 5.66(2015):53477-53483.