6-aminoquinolones as new potential anti-HIV agents
6-aminoquinolones as new potential anti-HIV agents
复制标题
DOI：
10.1021/jm9903390
复制
发表时间：
2000-10-05
影响因子：
7.3
通讯作者：
Palu, G
中科院分区：
文献类型：
--
作者：
Cecchetti, V;Parolin, C;Palu, G
研究了一系列6-氨基喹诺酮类化合物体外抗人类免疫缺陷病毒1型（HIV-1）的活性。化合物12a在N-1位置上有一个甲基取代基，在C-7位置上有一个4-（2-吡啶基）-1-哌嗪片段，对抑制HIV-1在新感染的C8166人淋巴母细胞细胞系上的复制最有效。12a EC50值为0.1 μ M，与N-1位置分别含有环丙基和叔丁基取代基的化合物8a和7a相比，EC50浓度降低了7-20倍。当C-6氨基被氟原子取代时，观察到抗病毒效果下降。观察到的效果是选择性的，因为在测试化合物对抗1型单纯疱疹病毒（HSV-1）时，效力大大降低。活性喹诺酮类衍生物与TAR RNA的相互作用非常有效，这表明其作用机制是核酸靶向的。
A series of 6-aminoquinolone compounds were evaluated for their in vitro activity against human immunodeficiency virus type 1 (HIV-1). Compound 12a, bearing a methyl substituent at the N-1 position and a 4-(2-pyridyl)-1-piperazine moiety at the C-7 position, was the most active in inhibiting HIV-1 replication on de novo infected C8166 human lymphoblastoid cell lines. The 12a EC50 value was 0.1 mu M, a 7-20-fold lower concentration relative to that for compounds 8a and 7a containing a cyclopropyl and tert-butyl substituent at the N-1 position, respectively. When the C-6 amino group was replaced with a fluorine atom, a decreased antiviral effect was observed. The observed effects are selective, since potency is substantially reduced when testing the compounds against the herpes simplex virus type 1 (HSV-1). Active quinolone derivatives very efficiently interact with TAR RNA, which suggests a nucleic acid-targeted mechanism of action.