Thiazolobenzimidazole: biological and biochemical anti-retroviral activity of a new nonnucleoside reverse transcriptase inhibitor.
Thiazolobenzimidazole: biological and biochemical anti-retroviral activity of a new nonnucleoside reverse transcriptase inhibitor.
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噻唑并苯并咪唑：一种新型非核苷逆转录酶抑制剂的生物和生化抗逆转录病毒活性。
DOI：
10.1016/0166-3542(93)90031-d
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发表时间：
1993
影响因子：
7.6
通讯作者：
Shannon,WM
中科院分区：
文献类型：
--
作者：
BuckheitJr,RW;Hollingshead,MG;Germany-Decker,J;White,EL;McMahon,JB;Allen,LB;Ross,LJ;Decker,WD;Westbrook,L;Shannon,WM
噻唑苯并咪唑（NSC 625487）是一种高效的人类免疫缺陷病毒诱导的细胞杀伤和病毒复制抑制剂，适用于多种人类细胞系以及新鲜的人外周血淋巴细胞和巨噬细胞。该化合物对一组生物多样性的实验室和临床HIV-1毒株有活性，包括抗azt毒株G910-6。然而，该药物对HIV-2和HIV-1的吡啶酮耐药菌株（A17）无活性，该菌株对几种结构不同的常见非核苷类逆转录酶抑制剂具有交叉耐药。该化合物选择性地抑制HIV-1逆转录酶，而非HIV-2逆转录酶。噻唑苯并咪唑与AZT或ddI联合使用可协同抑制体外HIV-1诱导的细胞杀伤。噻唑苯并咪唑还能抑制劳舍尔小鼠白血病逆转录病毒的复制。因此，噻唑苯并咪唑是一种新的活性抗hiv -1化学型，可能代表了具有增强抗逆转录病毒活性范围的非核苷类逆转录酶抑制剂的一个亚类。
Thiazolobenzimidazole (NSC 625487) was a highly potent inhibitor of human immunodeficiency virus-induced cell killing and viral replication in a variety of human cell lines, as well as fresh human peripheral blood lymphocytes and macrophages. The compound was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6. However, the agent was inactive against HIV-2 and a pyridinone-resistant strain (A17) of HIV-1, a strain which is cross-resistant to several structurally diverse members of a common pharmacologic class of nonnucleoside reverse transcriptase inhibitors. The compound selectively inhibited HIV-1 reverse transcriptase but not HIV-2 reverse transcriptase. Combinations of thiazolobenzimidazole with either AZT or ddI synergistically inhibited HIV-1 induced cell killing in vitro. Thiazolobenzimidazole also inhibited the replication of the Rauscher murine leukemia retrovirus. Thus, thiazolobenzimidazole is a new active anti-HIV-1 chemotype and may represent a subclass of nonnucleoside reverse transcriptase inhibitors with an enhanced range of anti-retroviral activity.