9-(1,3-二羟基-2-丙氧基甲基)鸟嘌呤与阿昔洛韦对人、猴和啮齿动物巨细胞病毒的活性比较。
Activity of 9-(1,3-dihydroxy-2-propoxymethyl)guanine compared with that of acyclovir against human, monkey, and rodent cytomegaloviruses.
作者信息
Freitas V R, Smee D F, Chernow M, Boehme R, Matthews T R
出版信息
Antimicrob Agents Chemother. 1985 Aug;28(2):240-5. doi: 10.1128/AAC.28.2.240.
Abstract
The activities of the purine acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) against two human and five animal strains of cytomegalovirus were compared with those of acyclovir. DHPG was significantly more active than acyclovir against all but one (mouse cytomegalovirus) of the strains tested, with 50% effective doses ranging from 5 to 13 microM, as determined by plaque reduction assays in human embryonic lung (MRC-5) and human embryonic tonsil cells. Both DHPG and acyclovir inhibited virus replication at concentrations considerably lower than those necessary to inhibit cell proliferation. In mode-of-action studies, the triphosphates of DHPG and acyclovir inhibited human cytomegalovirus DNA polymerase. DHPG phosphorylation to the active triphosphate was enhanced in infected cells; however, this enzymatic activity was unrelated to thymidine kinase. In animal studies, DHPG was slightly more effective than acyclovir in reducing mouse cytomegalovirus-induced mortality.
摘要
将嘌呤无环核苷9-(1,3-二羟基-2-丙氧甲基)鸟嘌呤（DHPG）对两株人巨细胞病毒毒株和五株动物巨细胞病毒毒株的活性与阿昔洛韦进行了比较。通过在人胚肺（MRC-5）细胞和人胚扁桃体细胞中进行蚀斑减少试验测定，除一种毒株（小鼠巨细胞病毒）外，DHPG对所有测试毒株的活性均显著高于阿昔洛韦，其50%有效剂量范围为5至13微摩尔。DHPG和阿昔洛韦均在远低于抑制细胞增殖所需浓度时就能抑制病毒复制。在作用机制研究中，DHPG和阿昔洛韦的三磷酸盐均能抑制人巨细胞病毒DNA聚合酶。在感染细胞中，DHPG磷酸化为活性三磷酸盐的过程增强；然而，这种酶活性与胸苷激酶无关。在动物研究中，DHPG在降低小鼠巨细胞病毒诱导的死亡率方面比阿昔洛韦稍有效。
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