Mechanism of action of the nitrosoureas -- III. Reactions of bis-chloroethyl nitrosourea and bis-fluoroethyl nitrosourea with adenosine.
Mechanism of action of the nitrosoureas -- III. Reactions of bis-chloroethyl nitrosourea and bis-fluoroethyl nitrosourea with adenosine.
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亚硝基脲类药物的作用机制——III．
DOI：
10.1016/0006-2952(79)90325-3
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发表时间：
1979
影响因子：
5.8
通讯作者：
D. Ludlum
中科院分区：
文献类型：
--
作者：
W. Tong;D. Ludlum
本系列之前的论文为治疗性亚硝基脲与胞苷和鸟苷相互作用形成卤乙基核苷衍生物提供了证据。这些衍生物对于解释双氯乙基亚硝基脲（BCNU）、双氟乙基亚硝基脲（BFNU）和相关治疗剂的细胞毒性作用可能很重要。我们现在报道了 BCNU 和 BFNU 与腺苷反应形成 1-卤乙基腺苷。这些1-取代的卤乙基腺苷环化形成1,N6-乙基腺苷：1-氯乙基腺苷在37°中性水溶液中半衰期为20分钟，1-氟乙基腺苷在相同条件下半衰期为20小时。 1-羟乙基腺苷也是 BCNU 或 BFNU 与腺苷反应的主要产物，但它不是由 1-卤乙基腺苷水解形成。因此，提出了涉及环化亚硝基脲衍生物的反应机制来解释该衍生物和其他羟乙基核苷的形成。
Previous papers in this series have provided evidence for the formation of haloethyl nucleoside derivatives from the interaction of the therapeutic nitrosoureas with cytidine and guanosine. Such derivatives could be important in explaining the cytotoxic action of bis-chloroethyl nitrosourea (BCNU), bis-fluoroethyl nitrosourea (BFNU), and related therapeutic agents. We now report the formation of 1-haloethyl adenosines from the reaction of BCNU and BFNU with adenosine. These 1-substituted haloethyl adenosines cyclize to form 1,N6-ethanoadenosine: 1-chloroethyladenosine with a half-life of 20 min in neutral aqueous solution at 37°, and 1-fluoroethyladenosine with a half-life of 20 hr under the same conditions. 1-Hydroxyethyladenosine is also a major product of the reaction of either BCNU or BFNU with adenosine, but it is not formed from the hydrolysis of either 1-haloethyladenosine. Accordingly, a reaction mechanism involving a cyclized nitrosourea derivative is proposed to explain the formation of this and other hydroxyethyl nucleosides.