Pyrimidine acyclonucleosides, inhibitors of uridine phosphorylase.
Pyrimidine acyclonucleosides, inhibitors of uridine phosphorylase.
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嘧啶无环核苷，尿苷磷酸化酶抑制剂。
DOI：
10.1016/0006-2952(81)90228-8
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发表时间：
1981
影响因子：
5.8
通讯作者：
Cha,S
中科院分区：
文献类型：
--
作者：
Niedzwicki,JG;elKouni,MH;Chu,SH;Cha,S
一类新的核苷类似物，吡啶亚胺无环核苷，是尿苷磷酸化酶的竞争性抑制剂，但对胸腺嘧啶磷酸化酶、尿苷激酶或胸苷激酶没有影响。该系列中效力最强的是acyclothydine [5-甲基-1-（2′-羟基乙氧基甲基）尿嘧啶]，aKi值为3 μM。估计在嘧啶环5位取代的其他类似物的Ki值小于30 μM。测定了6种人肿瘤异种移植物提取物的尿嘧啶磷酸化酶和胸腺嘧啶磷酸化酶的组织水平，以及酰基尿苷[1-（2′-羟乙氧基甲基）尿嘧啶]对5-氟-2 ′-脱氧尿苷（FUdR）磷酸化活性的抑制作用。FUdR切割抑制最多的组织中，胸苷磷酸化酶尿酸磷酸化酶的比例低。讨论了这些尿酸磷酸化酶抑制剂与化疗药物FUdR的潜在用途。
A new class of nucleoside analogs, the pyridimine acyclonucleosides, are competitive inhibitors of uridine phosphorylase but have no effect on thymicline phosphorylase, uridine kinase or thymidine kinase. The most potent of the series is acyclothymidine [5-methyl-1-(2′-hydroxyethoxymethyl)uracil] with aKivalue of 3 μM.Kivalues of less than 30 μM were estimated for other analogs substituted at the 5-position of the pyrimicline ring. Extracts of xenografts of six human tumors were assayed for tissue levels of uricline phosphorylase and thymicline phosphorylase and for inhibition of 5-fluoro-2′-deoxyuridine (FUdR) phosphorolytic activity by acyclouridine [1-(2′-hydroxyethoxymethyl) uracil]. FUdR cleavage was inhibited most in those tissues in which the ratio of thymidine phosphorylase to uricline phosphorylase was low. Potential usage of these uricline phosphorylase inhibitors with the chemotherapeutic agent FUdR is discussed.