INHIBITION OF HIV-1 REPLICATION BY A NONNUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITOR
INHIBITION OF HIV-1 REPLICATION BY A NONNUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITOR
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DOI：
10.1126/science.1701568
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发表时间：
1990-12-07
期刊：
影响因子：
56.9
通讯作者：
SULLIVAN, JL
中科院分区：
文献类型：
--
作者：
MERLUZZI, VJ;HARGRAVE, KD;SULLIVAN, JL
一系列双吡啶并二氮杂卓酮类化合物已被证明是人类免疫缺陷病毒-1（HIV-1）逆转录酶（RT）的有效抑制剂。一种化合物BI-RG-587对HIV-1 RT的抑制Ki为200纳摩尔，与三磷酸环氧鸟苷相比是非竞争性的。BI-RG-587对HIV-1 RT具有特异性，对猫和猿RT或任何哺乳动物DNA聚合酶均无影响。BI-RT-587在体外抑制HIV-1复制，如原位杂交、抑制蛋白质p24产生以及培养的人T细胞系和新鲜分离的人外周血淋巴细胞中缺乏合胞体形成所示。BI-RG-587对人细胞的细胞毒性研究显示，培养物中的治疗指数较高（> 8000）。
A series of dipyridodiazepinones have been shown to be potent inhibitors of human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT). One compound, BI-RG-587, had a Ki of 200 nanomolar for inhibition of HIV-1 RT that was noncompetitive with respect to eoxyguanosine triphosphate. BI-RG-587 was specific for HIV-1 RT, having no effect on feline and simian RT or any mammalian DNA polymerase. BI-RT-587 inhibited HIV-1 replication in vitro as demonstrated by in situ hybridization, inhibition of protein p24 production, and the lack of syncytia formation in cultured human T cell lines and freshly isolated human peripheral blood lymphocytes. Cytotoxicity studies of BI-RG-587 on human cells showed a high therapeutic index (> 8000) in culture.