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题名: Design, synthesis and biological evaluation of esculetin derivatives as anti-tumour agents
作者: Wang, Ping1;  Xia, Yang-Liu1;  Yu, Yang1;  Lu, Jun-Xia1;  Zou, Li-Wei1;  Feng, Lei1;  Ge, Guang-Bo1;  Yang, Ling1
刊名: RSC ADVANCES
发表日期: 2015
DOI: 10.1039/c5ra06070b
卷: 5, 期:66, 页:53477-53483
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Physical Sciences
类目[WOS]: Chemistry, Multidisciplinary
研究领域[WOS]: Chemistry
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.
关键词[WOS]: LEUKEMIA U937 CELLS ;  LIPOXYGENASE INHIBITOR ;  SIMPLE COUMARINS ;  APOPTOSIS ;  SERIES ;  HYDROXYCOUMARINS ;  GLUCURONIDATION ;  INDUCTION ;  LINES
语种: 英语
WOS记录号: WOS:000356801300040
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/146347
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China

Recommended Citation:
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.
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