Reversible Inhibitory Effects of Saturated and Unsaturated Alkyl Esters on the Carboxylesterases Activity in Rat Intestine

doi:10.1007/s11745-010-3434-z

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	Reversible Inhibitory Effects of Saturated and Unsaturated Alkyl Esters on the Carboxylesterases Activity in Rat Intestine
	Li, Ping; Zhu, Chun-liu; Zhang, Xin-xin; Gan, Li; Yu, Hong-zhen; Gan, Yong
刊名	LIPIDS
	2010-07
卷号	45 期号:7 页码:603-612
关键词	Carboxylesterases Metabolism Enzyme inhibitor Ethyl esters Methyl esters Inhibitory mechanism In situ intestine Adefovir dipivoxil
ISSN号	0024-4201
DOI	10.1007/s11745-010-3434-z
文献子类	Article
英文摘要	This study was conducted to investigate the relationship between the carbon chain length/double bonds of alkyl esters and their inhibitory potency/mechanism on carboxylesterases (CESs). CESs activity was evaluated by inhibition of adefovir dipivoxil (ADV) metabolism in rat intestinal homogenates. Furthermore, the inhibitory effect of BNPP and ethyl (E)-hex-2-enoate (C8:1) on drug absorption was evaluated in situ intestinal perfusion model. The results showed that the rank order of the inhibitory potency on CESs was C10:0 > C8:0 > C6:0 > C4:0 > C12:0, C8:1 > C8:0, C6:1 > C6:0, while the esters (C14:0, C13:1, C16:0, C18:0, C17:1, C20:0) were found to have no inhibitory effect at investigated concentrations. However, the unsaturated esters (C20:1, C20:2, C20:3) displayed the inhibitory effect on CESs. Moreover, the double reciprocal plots indicated that alky esters inhibited the CESs in competitive and mixed competitive ways which were reversible. In addition, the result of most effective CESs inhibitor C8:1 from in situ experiment showed that C8:1 can inhibit the CESs-mediated intestinal metabolism and improve the drug absorption. And the inhibition had no time-dependent effect, compared with that of BNPP groups. The study suggested that alkyl esters can be served as effective and reversible CESs inhibitors, besides that their inhibitory potency/mechanism can be affected by their carbon chain length/double bonds.
资助项目	National Natural Sciences Foundation of China[30701054] ; National Science & Technology Major Project[2009ZX09301-001] ; National Basic Research Program of China[2009CB930300]
WOS关键词	PRODRUG TENOFOVIR DISOPROXIL ; IN-VITRO ; SELECTIVE-INHIBITION ; FATTY-ACIDS ; METABOLISM ; ABSORPTION ; LIVER ; BENZIL ; HYDROLYSIS ; MODULATION
WOS研究方向	Biochemistry & Molecular Biology ; Nutrition & Dietetics
语种	英语
出版者	SPRINGER HEIDELBERG
WOS记录号	WOS:000279695400004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278862]
专题	药物制剂研究中心成果转移转化处
通讯作者	Gan, Yong
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Li, Ping,Zhu, Chun-liu,Zhang, Xin-xin,et al. Reversible Inhibitory Effects of Saturated and Unsaturated Alkyl Esters on the Carboxylesterases Activity in Rat Intestine[J]. LIPIDS,2010,45(7):603-612.
APA	Li, Ping,Zhu, Chun-liu,Zhang, Xin-xin,Gan, Li,Yu, Hong-zhen,&Gan, Yong.(2010).Reversible Inhibitory Effects of Saturated and Unsaturated Alkyl Esters on the Carboxylesterases Activity in Rat Intestine.LIPIDS,45(7),603-612.
MLA	Li, Ping,et al."Reversible Inhibitory Effects of Saturated and Unsaturated Alkyl Esters on the Carboxylesterases Activity in Rat Intestine".LIPIDS 45.7(2010):603-612.