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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
Source PublicationRSC ADVANCES
2015
DOI10.1039/c5ra06070b
Volume5Issue:66Pages:53477-53483
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Physical Sciences
WOS SubjectChemistry, Multidisciplinary
WOS Research AreaChemistry
WOS KeywordLEUKEMIA U937 CELLS ; LIPOXYGENASE INHIBITOR ; SIMPLE COUMARINS ; APOPTOSIS ; SERIES ; HYDROXYCOUMARINS ; GLUCURONIDATION ; INDUCTION ; LINES
AbstractEsculetin, 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.
Language英语
WOS IDWOS:000356801300040
Citation statistics
Cited Times:7[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/146347
Collection中国科学院大连化学物理研究所
AffiliationChinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
Recommended Citation
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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