Reversible Inhibitory Effects of Saturated and Unsaturated Alkyl Esters on the Carboxylesterases Activity in Rat Intestine
文献类型：期刊论文
| 作者 | Li, Ping; Zhu, Chun-liu ; Zhang, Xin-xin; Gan, Li; Yu, Hong-zhen; Gan, Yong
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| 刊名 | LIPIDS
 |
| 出版日期 | 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. |
| WOS关键词 | PRODRUG TENOFOVIR DISOPROXIL ; IN-VITRO ; SELECTIVE-INHIBITION ; FATTY-ACIDS ; METABOLISM ; ABSORPTION ; LIVER ; BENZIL ; HYDROLYSIS ; MODULATION |
| 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研究方向 | Biochemistry & Molecular Biology ; Nutrition & Dietetics |
| 语种 | 英语 |
| WOS记录号 | WOS:000279695400004 |
| 出版者 | SPRINGER HEIDELBERG |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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