In Vitro Evaluation of the Effect of 7-Methyl Substitution on Glucuronidation of Daphnetin: Metabolic Stability, Isoform Selectivity, and Bioactivity Analysis
文献类型：期刊论文
| 作者 | Liang, Si-Cheng1,2,3; Ge, Guang-Bo2; Xia, Yang-Liu2,3; Zhang, Jiang-Wei2; Qi, Xiao-Yi1; Tu, Cai-Xia1; Yang, Ling2 |
| 刊名 | journal of pharmaceutical sciences
 |
| 出版日期 | 2015-10-01 |
| 卷号 | 104期号:10页码:3557-3564 |
| 关键词 | daphnetin glucuronidation methyl substitution structural modification metabolic stability phase II enzymes glucuronosyltransferases human liver microsomes enzyme kinetics metabolic clearance |
| 英文摘要 | the c-8 phenol group is essential to exert the bioactivities of daphnetin, but it is readily conjugated with glucuronic acid prior to excretion. in this study, daphnetin-7-methylether (7m-dnp) was used to investigate the effect of 7-methyl substitution on daphnetin glucuronidation in human/rat liver (hlm/rlm) and intestine (him/rim) microsomes, and recombinant udp-glucuronosyltransferases (ugts). compared with daphnetin, the v-max/k-m values of 7m-dnp via 8-o-glucuronidation were 2.1-fold lower in hlm, 1.7-fold lower in him, and 2.4-fold lower in rlm, suggesting an improvement in metabolic stability. different from daphnetin 8-o-glucuronidation exclusively catalyzed by ugt1a6 and ugt1a9, ugt1a1, -1a3, -1a7, -1a8, and -1a9 showed glucuronidation activity toward 7m-dnp. kinetics studies, chemical inhibition, and the relative activity factor approach were used to demonstrate that ugt1a9 was mainly responsible for the reaction in hlm, whereas ugt1a1 was a primary contributor in him. the v-max/k-m values of 7m-dnp glucuronidation in hlm and him were 0.61-0.74-fold lower than those of rat, suggesting the differences between the two species. the bioactivity analysis demonstrated that 7m-dnp had an anti-inflammatory activity comparable to that of daphnetin. these findings indicated that the outcomes of 7-methyl substitution on daphnetin might be positive, but this should be confirmed in future in vivo studies. (c) 2015 wiley periodicals, inc. |
| WOS标题词 | science & technology ; life sciences & biomedicine ; physical sciences |
| 类目[WOS] | chemistry, medicinal ; chemistry, multidisciplinary ; pharmacology & pharmacy |
| 研究领域[WOS] | pharmacology & pharmacy ; chemistry |
| 关键词[WOS] | human udp-glucuronosyltransferases ; tandem mass-spectrometry ; coumarin derivatives ; biological-activity ; liver-microsomes ; protein-kinase ; identification ; inhibitor ; expression ; acid |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000360991400028 |
| 公开日期 | 2016-05-09 |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/146525]  |
| 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 |
| 作者单位 | 1.Dalian Med Univ, Affiliated Hosp 2, Dalian, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liang, Si-Cheng,Ge, Guang-Bo,Xia, Yang-Liu,et al. In Vitro Evaluation of the Effect of 7-Methyl Substitution on Glucuronidation of Daphnetin: Metabolic Stability, Isoform Selectivity, and Bioactivity Analysis[J]. journal of pharmaceutical sciences,2015,104(10):3557-3564. |
| APA | Liang, Si-Cheng.,Ge, Guang-Bo.,Xia, Yang-Liu.,Zhang, Jiang-Wei.,Qi, Xiao-Yi.,...&Yang, Ling.(2015).In Vitro Evaluation of the Effect of 7-Methyl Substitution on Glucuronidation of Daphnetin: Metabolic Stability, Isoform Selectivity, and Bioactivity Analysis.journal of pharmaceutical sciences,104(10),3557-3564. |
| MLA | Liang, Si-Cheng,et al."In Vitro Evaluation of the Effect of 7-Methyl Substitution on Glucuronidation of Daphnetin: Metabolic Stability, Isoform Selectivity, and Bioactivity Analysis".journal of pharmaceutical sciences 104.10(2015):3557-3564. |
入库方式： OAI收割
来源：大连化学物理研究所
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