A TIBO derivative, R82913, is a potent inhibitor of HIV-1 reverse transcriptase with heteropolymer templates.
A TIBO derivative, R82913, is a potent inhibitor of HIV-1 reverse transcriptase with heteropolymer templates.
复制标题
TIBO 衍生物 R82913 是一种具有杂聚物模板的 HIV-1 逆转录酶的有效抑制剂。
DOI：
10.1016/0166-3542(91)90005-c
复制
发表时间：
1991
影响因子：
7.6
通讯作者：
Chirigos,MA
中科院分区：
文献类型：
--
作者：
White,EL;BuckheitJr,RW;Ross,LJ;Germany,JM;Andries,K;Pauwels,R;Janssen,PA;Shannon,WM;Chirigos,MA
R82913，(+)-S-4,5,6,7-四氢-9-氯-5-甲基-6-(3-甲基-2-丁烯基)-咪唑并[4,5,1-jk][1,4]-苯二氮卓-2(1H)-硫酮（TIBO衍生物），抑制CEM细胞中13种不同HIV-1病毒株的复制，中值IC50为0.15μM。杀死 50% 细胞的化合物浓度要高得多（46 μM），表明 R82913 具有高选择性指数。在使用天然存在的模板（核糖体 RNA）的测定中，R82913 抑制 HIV-1 逆转录酶的效力比 AZT-TP 强 20 倍，该模板比合成均聚物更准确地类似于天然病毒 RNA。使用该模板，R82913 抑制 HIV-1 逆转录酶的 ID50 (0.01 μM) 等于或低于该化合物在我们所有细胞培养测定中的 IC50 (0.01-0.65 μM)。 R82913 对 CEM 细胞中 HIV-2 的复制没有影响，并且不会抑制该病毒的逆转录酶。
R82913, (+)-S-4,5,6,7-tetrahydro-9-chloro-5-methyl-6-(3-methyl-2-butenyl)-imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (a TIBO derivative), inhibited the replication of thirteen different strains of HIV-1 in CEM cells with a median IC50of 0.15 μM. The concentration of compound that killed 50% of the cells was much higher (46 μM), indicating that R82913 has a high selectivity index. R82913 was 20-fold more potent than AZT-TP in the inhibition of HIV-1 reverse transcriptase in an assay using a naturally occurring template (ribosomal RNA) that more accurately resembles native viral RNA than a synthetic homopolymer. With this template, R82913 inhibited HIV-1 reverse transcriptase with an ID50(0.01 μM) that is equal to, or lower than, the IC50for this compound in all of our cell culture assays (0.01-0.65 μM). R82913 has no effect on the replication of HIV-2 in CEM cells and does not inhibit the reverse transcriptase from this virus.