Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics.
Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics.
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自旋标记的 1-烷基-1-亚硝基脲抗肿瘤抗生素增效剂。
DOI：
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
R. Koldamova
中科院分区：
文献类型：
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作者：
V. Gadjeva;R. Koldamova
描述了一种合成抗肿瘤药物 1-(2-氯乙基)-3-环己基-1-亚硝基脲 (CCNU) 的四种自旋标记结构类似物的新方法，使用亚硝酸乙酯对中间体自旋标记脲进行亚硝化。在人淋巴白血病肿瘤细胞中发现 1-乙基-3-[4-(2,2,6,6-四甲基哌啶-1-氧基)]-1-亚硝基脲 (3b) 对博来霉素和法莫霉素的细胞毒性具有体外协同作用。我们通过电子顺磁共振方法测量了C57BL小鼠器官匀浆中3b的组织分布。自旋标记的亚硝基脲主要位于肺部。我们的结果有力地支持了一种新方法的开发和验证，该方法用于合成毒性较低的亚硝基脲衍生物，作为抗肿瘤药物的潜在增效剂。
A new method for synthesis of four spin-labeled structural analogues of the antitumor drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), using ethyl nitrite for nitrosation of the intermediate spin-labeled ureas has been described. In vitro synergistic effects of 1-ethyl-3-[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (3b) on the cytotoxicity of bleomycin and farmorubicin were found in human lymphoid leukemia tumor cells. We measured the tissue distribution of 3b in organ homogenates of C57BL mice by an electron paramagnetic resonance method. The spin-labeled nitrosourea was mainly localized in the lungs. Our results strongly support the development and validation of a new approach for synthesis of less toxic nitrosourea derivatives as potential synergists of antitumor drugs.