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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
DOI10.1039/c5ra06070b
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
关键词[WOS]LEUKEMIA U937 CELLS ; LIPOXYGENASE INHIBITOR ; SIMPLE COUMARINS ; APOPTOSIS ; SERIES ; HYDROXYCOUMARINS ; GLUCURONIDATION ; INDUCTION ; LINES
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.
语种英语
WOS记录号WOS:000356801300040
引用统计
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/146347
专题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
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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.
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