Novel HIV-1 integrase inhibitors derived from quinolone antibiotics
Novel HIV-1 integrase inhibitors derived from quinolone antibiotics
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DOI：
10.1021/jm0600139
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发表时间：
2006-03-09
影响因子：
7.3
通讯作者：
Shinkai, H
中科院分区：
文献类型：
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作者：
Sato, M;Motomura, T;Shinkai, H
病毒酶整合酶是人类免疫缺陷病毒1型（HIV-1）复制所必需的，是抗逆转录病毒药物的剩余靶标。在这里，我们描述了喹诺酮类抗生素的修改，以产生新的整合酶抑制剂JTK-303（GS 9137），阻断链转移的病毒酶。它具有喹诺酮类抗生素的核心结构，在链转移试验中显示出7.2 nM的IC 50，在急性HIV-1感染试验中显示出0.9 nM的EC 50。
The viral enzyme integrase is essential for the replication of human immunodeficiency virus type 1 (HIV-1) and represents a remaining target for antiretroviral drugs. Here, we describe the modification of a quinolone antibiotic to produce the novel integrase inhibitor JTK-303 (GS 9137) that blocks strand transfer by the viral enzyme. It shares the core structure of quinolone antibiotics, exhibits an IC50 of 7.2 nM in the strand transfer assay, and shows an EC50 of 0.9 nM in an acute HIV-1 infection assay.