期刊
ANTIVIRAL RESEARCH
卷 144, 期 -, 页码 164-172出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2017.06.014
关键词
HBV; RNaseH; Tropolones; Antiviral; QSAR
资金
- [R01 AI122669]
- [SC1 GM111158]
Chronic Hepatitis B virus (HBV) infection is a major worldwide public health problem. Current direct acting anti-HBV drugs target the HBV DNA polymerase activity, but the equally essential viral ribonuclease H (RNaseH) activity is unexploited as a drug target. Previously, we reported that alpha-hydroxytropolone compounds can inhibit the HBV RNaseH and block viral replication. Subsequently, we found that our biochemical RNaseH assay underreports efficacy of the alpha-hydroxytropolones against HBV replication. Therefore, we conducted a structure-activity analysis of 59 troponoids against HBV replication in cell culture. These studies revealed that antiviral efficacy is diminished by larger substitutions on the tropolone ring, identified key components in the substitutions needed for high efficacy, and revealed that cytotoxicity correlates with increased lipophilicity of the alpha-hydroxytropolones. These data provide key guidance for further optimization of the alpha-hydroxytropolone scaffold as novel HBV RNaseH inhibitors. (C) 2017 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据