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哺乳动物代谢的微生物模型。使用雅致小克银汉霉将速尿进行N-脱烷基化反应以生成哺乳动物代谢物CSA。

Microbial models of mammalian metabolism. N-dealkylation of furosemide to yield the mammalian metabolite CSA using Cunninghamella elegans.

作者信息

Hezari M, Davis P J

机构信息

Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Texas, Austin 78712-1074.

出版信息

Drug Metab Dispos. 1992 Nov-Dec;20(6):882-8.

PMID:1362941
Abstract

Furosemide (Lasix), a widely used diuretic, is metabolized by the fungus Cunninghamella elegans (ATCC 36112) to 4-chloro-5-sulfamoyl anthranilic acid (CSA), a metabolite also present in mammalian systems. This metabolite was isolated following preparative-scale incubations of C. elegans, and was characterized by comparison with standard CSA using 13C-NMR, mass spectrometry (high-resolution mass spectra, electron impact mass spectra), UV, TLC, and HPLC with fluorescence detection. Because a known complication with furosemide studies is the spontaneous formation of CSA by decomposition of furosemide during incubation, extraction, and/or analysis, a time course study was conducted to determine the rate of CSA formation caused by metabolism vs. the relatively low rate of CSA formation caused by spontaneous decomposition.

摘要

速尿(速尿灵)是一种广泛使用的利尿剂,可被真菌雅致小克银汉霉(ATCC 36112)代谢为4-氯-5-氨磺酰邻氨基苯甲酸(CSA),该代谢物也存在于哺乳动物系统中。在对雅致小克银汉霉进行制备规模的培养后分离出了这种代谢物,并通过使用13C-NMR、质谱(高分辨率质谱、电子轰击质谱)、紫外光谱、薄层色谱和带荧光检测的高效液相色谱与标准CSA进行比较来对其进行表征。由于速尿研究中一个已知的并发症是在孵育、提取和/或分析过程中速尿分解会自发形成CSA,因此进行了一项时间进程研究,以确定由代谢引起的CSA形成速率与由自发分解引起的相对较低的CSA形成速率。

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