Metabolic Study of Stable Isotope Labeled Indolinone Derivative in Hepatocyte Cell by UPLC/Q TOF MS
文献类型：期刊论文
| 作者 | Yang, Jixia1; Zhang, Gongzheng1; Wang, Zhaoyang1; Meng, Jian2 ; Wen, Hongliang1
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| 刊名 | JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
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| 出版日期 | 2021-06-02 |
| 卷号 | 32期号:6页码:1538-1544 |
| ISSN号 | 1044-0305 |
| 关键词 | indolinone derivatives alpha-synuclein [C-3(2), N-15]-isotope labeling, metabolite UPLC/QTOF |
| DOI | 10.1021/jasms.1c00146 |
| 通讯作者 | Meng, Jian(goodwill_123@163.com) ; Wen, Hongliang(wen.hongliang@bit.edu.cn) |
| 英文摘要 | The aggregation process of alpha-synuclein (alpha-syn) is substantial in the pathogenesis of Parkinson's disease. Indolinone derivatives are inhibitors of a-syn aggregates and can be used as PET-based radiotracers for imaging alpha-syn fibrils. However, no investigations on the metabolism of indolinone derivatives have been reported until now. In the present research, a C-13 and N-15 isotope labeling strategy was developed to synthesize compound [C-13(2),N-15]-(Z)-1-(4-aminobenzyl)-3-(E)-(3-phenyl)allylidene)indolin-2-one (M0'), which was then used in a study of metabolism in hepatocytes. The metabolites were characterized using accurate mass and characteristic ion measurements. In the metabolic system, compound M0' was the main component (accounting for 97.5% of compound-related components) after incubation in hepatocytes for 3 h, which indicated that compound M0' possessed great metabolic stability. Seven metabolites have been successfully verified by UPLC/Q TOF MS in metabolic studies, including hydroxyl M0' (M1'), hydroxyl and methylated M0' (M2'), N-acetylated MO' (M3'), sulfate of hydroxyl M0' (M4'), the glucose conjugate of M0' (M5'), glucuronide conjugate of M0' (M6'), and glucuronide conjugate of hydroxyl M0' (M7'). The study on metabolism provides the important information to develop effective alpha-syn aggregate inhibitors and new PET-tracer-related indolinone derivatives. |
| WOS关键词 | MASS-SPECTROMETRY ; DRUG-METABOLISM ; DISCOVERY |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry ; Spectroscopy |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000714641000028 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/298692]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Meng, Jian; Wen, Hongliang |
| 作者单位 | 1.Beijing Inst Technol, Sch Chem & Chem Engn, Key Lab Med Mol Sci & Pharmaceut Engn, Minist Ind & Informat Technol, Beijing 102488, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Jixia,Zhang, Gongzheng,Wang, Zhaoyang,et al. Metabolic Study of Stable Isotope Labeled Indolinone Derivative in Hepatocyte Cell by UPLC/Q TOF MS[J]. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY,2021,32(6):1538-1544. |
| APA | Yang, Jixia,Zhang, Gongzheng,Wang, Zhaoyang,Meng, Jian,&Wen, Hongliang.(2021).Metabolic Study of Stable Isotope Labeled Indolinone Derivative in Hepatocyte Cell by UPLC/Q TOF MS.JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY,32(6),1538-1544. |
| MLA | Yang, Jixia,et al."Metabolic Study of Stable Isotope Labeled Indolinone Derivative in Hepatocyte Cell by UPLC/Q TOF MS".JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 32.6(2021):1538-1544. |
入库方式： OAI收割
来源：上海药物研究所
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