Separation and peroxisome proliferator-activated receptor-gamma agonist activity evaluation of synthetic racemic bavachinin enantiomers

doi:10.1016/j.bmcl.2015.04.029

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	Separation and peroxisome proliferator-activated receptor-gamma agonist activity evaluation of synthetic racemic bavachinin enantiomers
	Du, Guoxin 2; Feng, Li 2; Yang, Zhuo 1; Shi, Jiye 3; Huang, Cheng 2; Guo, Fujiang 2; Li, Bo 1; Zhu, Weiliang1 ; Li, Yiming 2
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2015-06-15
卷号	25 期号:12 页码:2579-2583
关键词	Bavachinin PPAR-gamma Supercritical fluid chromatography Binding assay Molecular docking
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2015.04.029
文献子类	Article
英文摘要	Bavachinin, isolated from Psoralea corylifolia seeds, has been reported to demonstrate peroxisome proliferator- activated receptor-gamma (PPAR-gamma) agonist activity. However, isolated bavachinin is actually a mixture of S and R configurations, with an enantiomeric excess value of approximately 24.3%. For further study on the structure-activity relationships of bavachinin, investigating the PPAR-gamma agonist activity of the two enantiomers is crucial. Considering the limited availability, racemic bavachinin was prepared in this study using chemical synthesis. The enantiomers of racemic bavachinin were then separated using supercritical fluid chromatography. This concise strategy yielded (S)- and (R)-bavachinin in optical purity as high as >= 97.5%. The PPAR-gamma agonist activity of the two enantiomers was evaluated using a time-resolved fluorescence resonance energy transfer-based competitive binding assay method; IC50 values of (S)-and (R)-bavachinin were 616.7 and 471.2 nM, respectively. The interaction between the compounds and PPAR-gamma was further explored using a molecular docking method. This study suggests that (S)-and (R)-bavachinin demonstrate similar PPAR-gamma agonist activities. (C) 2015 Elsevier Ltd. All rights reserved.
资助项目	National Natural Science Foundation of China[81173518] ; Eastern Scholar Tracking Program of Shanghai Municipal Education Commission[2012-90] ; International Collaboration Project[2014DFA31130] ; Program of Shanghai E-institute of Bioactive Constituents in Traditional Chinese Medicine[00000000]
WOS关键词	SUPERCRITICAL-FLUID CHROMATOGRAPHY ; PSORALEA-CORYLIFOLIA ; CHIRAL FLAVANONES ; DERIVATIVES ; HESPERETIN ; NARINGENIN ; CANCER ; ALPHA
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000355147300026
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276492]
专题	药物发现与设计中心天然药物化学研究室
通讯作者	Zhu, Weiliang
作者单位	1.Chinese Acad Sci, Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China; 3.UCB Pharma, Dept Informat, Slough SL1 4EN, Berks, England
推荐引用方式 GB/T 7714	Du, Guoxin,Feng, Li,Yang, Zhuo,et al. Separation and peroxisome proliferator-activated receptor-gamma agonist activity evaluation of synthetic racemic bavachinin enantiomers[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2015,25(12):2579-2583.
APA	Du, Guoxin.,Feng, Li.,Yang, Zhuo.,Shi, Jiye.,Huang, Cheng.,...&Li, Yiming.(2015).Separation and peroxisome proliferator-activated receptor-gamma agonist activity evaluation of synthetic racemic bavachinin enantiomers.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,25(12),2579-2583.
MLA	Du, Guoxin,et al."Separation and peroxisome proliferator-activated receptor-gamma agonist activity evaluation of synthetic racemic bavachinin enantiomers".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 25.12(2015):2579-2583.