Inhibition of cellular thymidylate synthesis by cytotoxic propenal derivatives of pyrimidine bases and deoxynucleosides.
Inhibition of cellular thymidylate synthesis by cytotoxic propenal derivatives of pyrimidine bases and deoxynucleosides.
复制标题
嘧啶碱基和脱氧核苷的细胞毒性丙烯醛衍生物抑制细胞胸苷酸合成。
DOI：
10.1016/0006-2952(91)90732-k
复制
发表时间：
1991
影响因子：
5.8
通讯作者：
Grollman,AP
中科院分区：
文献类型：
--
作者：
Kalman,TI;Marinelli,ER;Xu,B;Reddy,AR;Johnson,F;Grollman,AP
评价了一系列嘧啶碱基和脱氧核苷的细胞毒性丙烯醛（3-氧代丙-1-烯基）衍生物在完整和透化的小鼠白血病L1210细胞中阻断胸苷酸合成的能力。有几种是这一过程的有效抑制剂，可能有助于其细胞毒性。在完整和透化的L1210、L-M和L-M（TK−）细胞中，胸苷-3-丙烯醛（该系列的原型）的IC 50值分别为21、7.5和75 μM以及1.5、1.7和3.5 μM。相关的碱基类似物，胸腺嘧啶-1-丙烯醛，是博来霉素诱导的DNA链断裂的产物;本研究的结果与这种抗生素的作用方式有关。
A series of cytotoxic propenal (3-oxoprop-1-enyl) derivatives of pyrimidine bases and deoxynucleosides was evaluated for their ability to block thymidylate synthesis in intact and permeabilized murine leukemia L1210 cells. Several were potent inhibitors of this process, likely contributing to their cytotxicity. The IC50values of thymidine-3-propenal, the prototype of this series, in intact and permeabilized L1210, L-M and L-M(TK−) cells were 21, 7.5, and 75 μM and 1.5, 1.7, and 3.5 μM, respectively. The related base analoque, thymine-1-propenal, is a product of bleomycin-induced DNA strand-scission; the results of the present study bear on the mode of action of this antibiotic.