Structure-activity relationships of flavonoids as natural inhibitors against E. coli beta-glucuronidase

doi:10.1016/j.fct.2017.03.042

	Structure-activity relationships of flavonoids as natural inhibitors against E. coli beta-glucuronidase
	Wu, Da-Chang 2; Zou, Li-Wei 3; Dou, Tong-Yi 4; Yang, Ling 3; Zhang, Tong-Yan 1; Hou, Jie 2; Weng, Zi-Miao 2; Wang, Ping 3; Ge, Guang-Bo 4; Dai, Zi-Ru 4
刊名	FOOD AND CHEMICAL TOXICOLOGY
	2017-11-01
卷号	109 页码:975-983
关键词	Flavonoids E. Coli bE.a-glucuronidasE. Structure-inhibition Relationships Scutellarein Luteolin
ISSN号	0278-6915
DOI	10.1016/j.fct.2017.03.042
文献子类	Article
英文摘要	Bacterial beta-glucuronidases play key roles in the deconjugation of a variety of endogenous and drug glucuronides, thus have been recognized as important targets to modulate the enterohepatic circulation of various glucuronides. In this study, more than 30 natural flavonoids were collected and their inhibitory effects against E. coli beta-glucuronidase (EcGUS) were assayed. The results demonstrated that some flavonoids including scutellarein, luteolin, baicalein, quercetin and scutellarin displayed strong to moderate inhibitory effects against EcGUS, with the IC50 values ranging from 5.76 mu M to 29.64 mu M, while iso-flavones and dihydroflavones displayed weak inhibitory effects against EcGUS. Further investigation on inhibition kinetics revealed that scutellarein and luteolin functioned as potent competitive inhibitors against EcGUS-mediated PNPG hydrolysis, with the K-i values less than 3.0 mu M. Molecular docking simulations demonstrated that scutellarein and luteolin could be well-docked into the catalytic site of EcGUS, while the binding areas of these two natural inhibitors on EcGUS were highly overlapped with that of PNPG on EcGUS. Additionally, the structure-inhibition relationships of natural flavonoids against EcGUS are also summarized, which will be very helpful for the medicinal chemists to design and develop more potent flavonoid-type inhibitors against EcGUS. (C) 2017 Elsevier Ltd. All rights reserved.
WOS关键词	HUMAN UDP-GLUCURONOSYLTRANSFERASES ; HUMAN CARBOXYLESTERASE 2 ; CANCER DRUG TOXICITY ; DIETARY POLYPHENOLS ; INTESTINAL BACTERIA ; METABOLISM ; IRINOTECAN ; ENZYMES ; DISEASE ; LIVER
WOS研究方向	Food Science & Technology ; Toxicology
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000415911500019
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/169270]
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
通讯作者	Zhang, Tong-Yan; Hou, Jie
作者单位	1.Zhengzhou Univ Light Ind, Zhengzhou 450001, Henan, Peoples R China 2.Dalian Med Univ, Dalian 116044, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
推荐引用方式 GB/T 7714	Wu, Da-Chang,Zou, Li-Wei,Dou, Tong-Yi,et al. Structure-activity relationships of flavonoids as natural inhibitors against E. coli beta-glucuronidase[J]. FOOD AND CHEMICAL TOXICOLOGY,2017,109:975-983.
APA	Wu, Da-Chang.,Zou, Li-Wei.,Dou, Tong-Yi.,Yang, Ling.,Zhang, Tong-Yan.,...&Dai, Zi-Ru.(2017).Structure-activity relationships of flavonoids as natural inhibitors against E. coli beta-glucuronidase.FOOD AND CHEMICAL TOXICOLOGY,109,975-983.
MLA	Wu, Da-Chang,et al."Structure-activity relationships of flavonoids as natural inhibitors against E. coli beta-glucuronidase".FOOD AND CHEMICAL TOXICOLOGY 109(2017):975-983.