化学
槲皮素
螯合作用
立体化学
NS5B
丙型肝炎病毒
类黄酮
结构-活动关系
苯甲酸
活动站点
组合化学
体外
生物化学
肝炎病毒
酶
有机化学
生物
病毒
病毒学
基因型
基因
抗氧化剂
作者
Dongwei Zhong,Mingming Liu,Yang Cao,Ye-lin Zhu,Shi‐Hui Bian,Jiayi Zhou,Feng‐Jie Wu,Kum-Chol Ryu,Lu Zhou,Deyong Ye
出处
期刊:Molecules
[MDPI AG]
日期:2015-04-16
卷期号:20 (4): 6978-6999
被引量:22
标识
DOI:10.3390/molecules20046978
摘要
Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin (2) could partly be attributed to it being a structural mimic of DKAs. In order to delineate the structural features required for the inhibitory effect and improve the anti-HCV potency, two novel types of quercetin analogues, 7-O-arylmethylquercetins and quercetin-3-O-benzoic acid esters, were designed, synthesized and evaluated for their anti-HCV properties in cell-based assays. Among the 38 newly synthesized compounds, 7-O-substituted derivative 3i and 3-O-substituted derivative 4f were found to be the most active in the corresponding series (EC50 = 3.8 μM and 9.0 μΜ, respectively). Docking studies suggested that the quercetin analogues are capable of establishing key coordination with the two magnesium ions as well as interactions with residues at the active site of HCV NS5B.
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