Discovery of potent nucleotide-mimicking competitive inhibitors of hepatitis C virus NS3 helicase
Discovery of potent nucleotide-mimicking competitive inhibitors of hepatitis C virus NS3 helicase
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DOI：
10.1016/j.bmcl.2010.09.002
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发表时间：
2011-05-01
影响因子：
2.7
通讯作者：
Maga, Giovanni
中科院分区：
文献类型：
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作者：
Gemma, Sandra;Butini, Stefania;Maga, Giovanni
在参与HCV生命周期的酶中，非结构蛋白NS 3具有蛋白酶和NTR/解旋酶的双重功能，是病毒复制所必需的。利用我们以前在开发具有最佳配体-酶相互作用所需的关键结构和电子特征的核苷酸模拟NS 3解旋酶（NS 3 h）抑制剂方面的知识，我们开发了四氢吖啶基衍生物3a，作为迄今报道的最有效的NS 3 h竞争性抑制剂（HCV NS 3 h K（i）= 20 nM）。(C)2010爱思唯尔有限公司版权所有。
Among the enzymes involved in the life cycle of HCV, the non-structural protein NS3, with its double function of protease and NTPase/helicase, is essential for the virus replication. Exploiting our previous knowledge in the development of nucleotide-mimicking NS3 helicase (NS3h) inhibitors endowed with key structural and electronic features necessary for an optimal ligand-enzyme interaction, we developed the tetrahydroacridinyl derivative 3a as the most potent NS3h competitive inhibitor reported to date (HCV NS3h K(i) = 20 nM). (C) 2010 Elsevier Ltd. All rights reserved.