Isolation, synthesis, and antitumor evaluation of spirohydantoin aziridine, a mutagenic metabolite of spirohydantoin mustard.
Isolation, synthesis, and antitumor evaluation of spirohydantoin aziridine, a mutagenic metabolite of spirohydantoin mustard.
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DOI：
10.1021/jm00157a039
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发表时间：
1986-07
影响因子：
7.3
通讯作者：
R. Struck;M. Kirk;L. S. Rice;W. J. Suling
中科院分区：
文献类型：
--
作者：
R. Struck;M. Kirk;L. S. Rice;W. J. Suling
螺旋海因芥子气（SHM）是一种具有抗癌活性的中枢神经系统导向氮芥，在小鼠肝线粒体后上清液（9000g级分）存在下代谢为非极性烷基化代谢物。通过孵育混合物的氯仿或乙酸乙酯提取物的薄层色谱法分离代谢产物，并通过质谱分析、合成和共色谱法确定其结构。代谢产物螺乙内酰脲氮丙啶在艾姆斯试验中对鼠伤寒沙门氏菌TA 1535具有致突变性，但在体内对P388白血病无抗肿瘤活性。
Spirohydantoin mustard (SHM), a central nervous system directed nitrogen mustard with anticancer activity, was metabolized in the presence of mouse liver postmitochondrial supernatant (9000g fraction) to a nonpolar alkylating metabolite. The metabolite was isolated by thin-layer chromatography of chloroform or ethyl acetate extracts of incubation mixtures, and its structure was established by mass spectral analysis, synthesis, and cochromatography. The metabolite, spirohydantoin aziridine, was mutagenic for Salmonella typhimurium TA1535 in the Ames assay but inactive as an antitumor agent against P388 leukemia in vivo.