Pyrrolo[2,3-d]pyrimidine nucleosides as inhibitors of human cytomegalovirus.
Pyrrolo[2,3-d]pyrimidine nucleosides as inhibitors of human cytomegalovirus.
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吡咯并[2,3-d]嘧啶核苷作为人巨细胞病毒的抑制剂。
DOI：
10.1128/aac.31.4.544
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发表时间：
1987
影响因子：
4.9
通讯作者：
Drach,JC
中科院分区：
文献类型：
--
作者：
Turk,SR;ShipmanJr,C;Nassiri,R;Genzlinger,G;Krawczyk,SH;Townsend,LB;Drach,JC
7种阿拉伯糖基、2′-脱氧核糖基和核糖基吡罗[2,3-d]嘧啶在体外对人巨细胞病毒的活性以及对原代和已建立的人来源细胞系的细胞毒性进行了评估。由于高细胞毒性，亲本核糖基类似物表现出很少的抗病毒选择性。相比之下，阿拉霉素、阿拉霉素、阿拉桑吉瓦霉素和脱氧桑吉瓦霉素在抗病毒作用（通过斑块或滴度降低或两者同时测量）和细胞毒性（通过显微镜和放射性前体掺入DNA、RNA和蛋白质测量）之间表现出选择性。这四种化合物的选择性（体外治疗指标）在2 ~ 40之间。这两种桑吉瓦霉素类似物是最有效和选择性的。例如，Ara-sangivamycin在浓度（10微米）下抑制病毒复制10(5)倍，但仅部分抑制细胞生长和标记前体掺入。通过DNA-DNA斑点杂交，发现四种阿拉伯糖核苷和脱氧核糖基核苷通过抑制病毒DNA合成而起作用。这四种类似物也通过空斑减少试验测试了对两种1型单纯疱疹病毒株的活性。出乎意料的是，所有化合物对单纯疱疹病毒的抑制程度都低于人巨细胞病毒。
Seven arabinosyl, 2'-deoxyribosyl, and ribosyl pyrrolo[2,3-d]pyrimidines were evaluated in vitro for activity against human cytomegalovirus and for cytotoxicity in primary and established cell lines of human origin. The parent ribosyl analogs exhibited little antiviral selectivity owing to high cytotoxicity. In contrast, ara-tubercidin, ara-toyocamycin, ara-sangivamycin, and deoxysangivamycin exhibited selectivity between antiviral effect (measured by plaque or titer reduction or both) and cytotoxicity (measured microscopically and by incorporation of radioactive precursors into DNA, RNA, and protein). The selectivity (in vitro therapeutic indexes) for these four compounds ranged from 2 to 40. The two sangivamycin analogs were the most potent and selective. Ara-sangivamycin, for example, inhibited virus replication 10(5)-fold at a concentration (10 microM) which produced only partial inhibition of cell growth and labeled precursor incorporation. The four arabinosyl and deoxyribosyl nucleosides appeared to act by inhibition of viral DNA synthesis as quantitated by DNA-DNA dot blot hybridization. These four analogs also were tested for activity against two strains of type 1 herpes simplex virus by a plaque reduction assay. Unexpectedly, all compounds inhibited herpes simplex virus to a lesser extent than human cytomegalovirus.