Cohen S S
Cancer. 1977 Jul;40(1 Suppl):509-18. doi: 10.1002/1097-0142(197707)40:1+<509::aid-cncr2820400717>3.0.co;2-8.
Certain D-arabinosyl nucleosides, notably arabinosyl cytosine (araC) and arabinosyl adenine (araA), are useful in the treatment of certain leukemias and some DNA virus infections, respectively. The compounds are lethal to animal cells and some bacteria. Despite extensive deamination, the parent nucleosides are transported within sensitive cells and phosphorylated to the mono-, di- and triphosphates. AraCTP and araATP are good specific competitive inhibitors of tumor cell of virus-induced DNA polymerases, competing with dCTP and dATP respectively. In addition to markedly inhibiting DNA synthesis, the aranucleotides enter newly formed DNA in internucleotide linkage. Sensitivity to the nucleosides appears to correlate with the relative ratio of formation of the triphosphate via a nucleoside kinase to degradation of the nucleoside via a nucleoside deaminase. Inhibition of the deaminase increases formation of the aranucleoside triphosphate in leukemic or virus-infected cells and markedly increases the toxicity of the nucleosides. Combinations of inhibitors of the deaminases and of the aranucleoside are being explored in clinical situations. In addition, the slow penetration of aranucleotides into cells has been observed and some of these 5'-phosphates are useful antiviral agents, e.g., against herpes virus in herpetic kiratitis.
某些D-阿拉伯糖基核苷，特别是阿糖胞苷（araC）和阿糖腺苷（araA），分别可用于治疗某些白血病和一些DNA病毒感染。这些化合物对动物细胞和某些细菌具有致死性。尽管会发生广泛的脱氨作用，但母体核苷仍可在敏感细胞内转运并磷酸化为一磷酸、二磷酸和三磷酸形式。阿糖胞苷三磷酸（AraCTP）和阿糖腺苷三磷酸（araATP）分别是病毒诱导的DNA聚合酶的肿瘤细胞的良好特异性竞争性抑制剂，它们分别与脱氧胞苷三磷酸（dCTP）和脱氧腺苷三磷酸（dATP）竞争。除了显著抑制DNA合成外，阿糖核苷酸还以核苷酸间连接的方式进入新形成的DNA中。对这些核苷的敏感性似乎与通过核苷激酶形成三磷酸的相对比例与通过核苷脱氨酶降解核苷的相对比例相关。抑制脱氨酶可增加白血病细胞或病毒感染细胞中阿糖核苷三磷酸的形成，并显著增加核苷的毒性。目前正在临床研究中探索脱氨酶抑制剂与阿糖核苷的联合使用。此外，还观察到阿糖核苷酸进入细胞的速度较慢，其中一些5'-磷酸酯是有用的抗病毒剂，例如可用于治疗疱疹性角膜炎中的疱疹病毒。
