POTENT AND SELECTIVE-INHIBITION OF HIV-1 REPLICATION INVITRO BY A NOVEL SERIES OF TIBO DERIVATIVES
POTENT AND SELECTIVE-INHIBITION OF HIV-1 REPLICATION INVITRO BY A NOVEL SERIES OF TIBO DERIVATIVES
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DOI：
10.1038/343470a0
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发表时间：
1990-02-01
期刊：
影响因子：
64.8
通讯作者：
JANSSEN, PAJ
中科院分区：
文献类型：
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作者：
PAUWELS, R;ANDRIES, K;JANSSEN, PAJ
在寻找抗人类免疫缺陷病毒活性化合物的过程中，我们发现了一系列新的tetrahydro-imidazo[4，5，1-jk][l，4]-benzodiazepin-2(1H)-one和硫酮(TIBO)衍生物的成员抑制艾滋病的主要病原体HIV-1的复制(参考文献1，2)，但对HIV-2的复制没有抑制作用(参考文献1，2)。3)，或任何其他DNA或RNA病毒。在五个细胞系统中，TiBO衍生物以纳摩尔量抑制HIV-1，其浓度低于细胞毒浓度的104-105倍。这些化合物前所未有的特异性可能是由于与逆转录酶相关的过程相互作用所致。相比之下，用于治疗艾滋病的AZT(3‘-叠氮-2’，3‘-二脱氧胸苷)和DDC(2’，3‘-二脱氧胞苷)和DDI(2’，3‘-二脱氧肌苷)在抑制HIV-1和HIV-2的浓度上都可以抑制HIV-1和HIV-2，根据细胞系统的不同，这些浓度比它们的细胞毒性浓度低2-4个数量级。TIBO-衍生物是与任何其他抗病毒药物无关的新化学物质。我们认为，它们是迄今为止研究过的最特异和最有效的HIV-1复制抑制剂。
IN the search for compounds active against human immunodeficiency virus (HIV), we have found that members of a novel series of tetrahydro-imidazo[4,5,1-jk][l,4]-benzodiazepin-2(1H)-one and -thione (TIBO) derivatives inhibit the replication of HIV-1 (refs 1, 2), the main aetiological agent of AIDS, but not of HIV-2 (ref. 3), or of any other DNA or RNA viruses. In five cell systems, HIV-1 is inhibited by TIBO derivatives in nanomolar amounts, which are 104–105times lower than the cytotoxic concentration. The unprecedented specificity of these compounds may be due to an interaction with a reverse transcriptase-associated process. By contrast, AZT (3′-azido-2′,3′-dideoxythymidine), which is used for the treatment of AIDS, and DDC (2′,3′-dideoxycytidine) and DDI (2′,3′-dideoxyinosine), whose clinical application is being assessed, inhibit both HIV-1 and HIV-2 at concentrations that, depending on the cell systems, are 2 to 4 orders of magnitude below their cytotoxic concentration5–8. TIBO-derivatives are new chemicals unrelated to any other antiviral agents. We believe that they are the most specific and potent inhibitors of HIV-1 replication studied so far.