Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors
Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors
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DOI：
10.1021/acsmedchemlett.7b00376
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发表时间：
2017-11-01
影响因子：
4.2
通讯作者：
Chen, Chin-Ho
中科院分区：
文献类型：
--
作者：
Dang, Zhao;Xie, Hua;Chen, Chin-Ho
作为开发新型抗HIV药物的一步，我们已经确定了一类喹啉类药物，包括丙二碱，它们通过阻断病毒进入来抑制1-5 μ M的HIV。在这项研究中，我们优化了aloperine的结构，并得到了活性显著提高的化合物。我们的结构优化已经产生了一种丙油碱衍生物19，其抗hiv -1活性提高了约15倍。我们的作用机制研究表明，化合物19不抑制HIV-1与受体的结合，但阻止病毒与膜的融合。该化合物与HIV-1gp120结合可能是其抗hiv -1进入活性的原因。
As a step toward developing novel anti-HIV agents, we have identified a class of quinolizidines, including aloperine, which inhibit HIV at 1-5 mu M by blocking viral entry. In this study, we have optimized the structure of aloperine and derived com-pounds with markedly improved activity. Our structural optimization has yielded an aloperine derivative 19 with approximate-ly a 15-fold increase in anti-HIV-1 activity. Our mechanism of action study reveals that compound 19 does not inhibit binding of HIV-1 to receptors, but arrest the virus from fusion with the membrane. Binding of the compound to HIV-1gp120 might be responsible for its anti-HIV-1 entry activity.