Differential antiviral activity of two TIBO derivatives against the human immunodeficiency and murine leukemia viruses alone and in combination with other anti-HIV agents.
Differential antiviral activity of two TIBO derivatives against the human immunodeficiency and murine leukemia viruses alone and in combination with other anti-HIV agents.
复制标题
两种 TIBO 衍生物单独和与其他抗 HIV 药物联合使用对人类免疫缺陷病毒和鼠白血病病毒的不同抗病毒活性。
DOI：
10.1089/aid.1993.9.1097
复制
发表时间：
1993
影响因子：
1.5
通讯作者：
Chirigos,MA
中科院分区：
文献类型：
--
作者：
BuckheitJr,RW;Germany-Decker,J;Hollingshead,MG;Allen,LB;Shannon,WM;Janssen,PA;Chirigos,MA
R82913和R86183是四氢咪唑并[4，5，1-jk][1，4]-苯并二氮杂卓-2（1H）-环庚三烯（TIBO）的两种衍生物，被发现有效地和选择性地抑制一组生物多样性的HIV-1实验室和临床菌株的复制和细胞杀伤作用。这两种化合物在所有检测的人细胞系以及新鲜人外周血淋巴细胞和巨噬细胞中均表现出显著活性。在UV-XC空斑形成和病毒产量降低试验中，发现这两种化合物之一（R82913）可显著抑制鼠逆转录病毒（Rauscher鼠白血病病毒）的复制。尽管R86183与R82913的不同之处仅在于单个氯分子的定位，但R86183对鼠逆转录病毒没有活性，但抑制HIV-1复制的效力高10倍。与其他逆转录酶抑制剂，包括AZT，ddC，和carbovir的组合抗病毒试验，产生协同抗HIV活性与两个TIBO衍生物。在与ddI和膦甲酸的组合中获得了轻微协同作用的结果，而在与硫酸葡聚糖的组合中检测到了拮抗活性的相加作用。
R82913 and R86183, two derivatives of tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepm-2(1H)-thione (TIBO), were found to potently and selectively inhibit the replication and cell killing effects of a panel of biologically diverse laboratory and clinical strains of HIV-1. The two compounds exhibited significant activity in all human cell lines tested, as well as in fresh human peripheral blood lymphocytes and macrophages. One of these two compounds (R82913) was found to significantly inhibit the replication of a murine retrovirus (Rauscher murine leukemia virus) in both UV-XC plaque formation and virus yield reduction assays. R86183, despite differing from R82913 only in the positioning of a single chlorine molecule, was not active against the murine retrovirus but was 10-fold more potent in inhibiting HIV-1 replication. Combination antiviral assays with other reverse transcriptase inhibitors, including AZT, ddC, and carbovir, yielded synergistic anti-HIV activity with both TIBO derivatives. Additive to slightly synergistic results were obtained in combinations with ddI and phosphonoformic acid whereas additive to antagonistic activity was detected in combination with dextran sulfate.