Pyridine hydroxamic acids are specific anti-HCV agents affecting HDAC6

被引：15

作者：

Kozlov, Maxim V. ^{[1
]}

Kleymenova, Alla A. ^{[1
]}

Romanova, Lyudmila I. ^{[2
]}

Konduktorov, Konstantin A. ^{[1
]}

Kamarova, Kamila A. ^{[1
]}

Smirnova, Olga A. ^{[1
]}

Prassolov, Vladimir S. ^{[1
]}

Kochetkov, Sergey N. ^{[1
]}

机构：

[1] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia

[2] Russian Acad Med Sci, Chumakov Inst Poliomyelitis, Moscow 142782, Russia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 11期

基金：

俄罗斯基础研究基金会;

关键词：

Pyridine hydroxamic acids; Benzohydroxamic acids; Hepatitis C virus; Histone deacetylase 6; alpha-Tubulin; DEACETYLASE; ACETYLATION; INHIBITOR; POTENT;

D O I：

10.1016/j.bmcl.2015.04.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Recently we reported benzohydroxamic acids (BHAs) as potent and selective inhibitors of hepatitis C virus (HCV) replicon propagation. In this work 12 pyridine hydroxamic acids (PHAs) were synthesized and tested in full-genome replicon assay. It was found that PHAs possessed very similar anti-HCV properties compared to BHAs. Both classes of hydroxamic acids caused hyperacetylation of alpha-tubulin pointing to inhibition of histone deacetylase 6 (HDAC6) as part of their antiviral activity. The tested compounds did not inhibit the growth of poliovirus, displaying high selectivity against HCV. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：2382 / 2385

页数：4

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