論文

査読有り
2015年8月

Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
  • Atsushi Furuta
  • Masayoshi Tsubuki
  • Miduki Endoh
  • Tatsuki Miyamoto
  • Junichi Tanaka
  • Kazi Abdus Salam
  • Nobuyoshi Akimitsu
  • Hidenori Tani
  • Atsuya Yamashita
  • Kohji Moriishi
  • Masamichi Nakakoshi
  • Yuji Sekiguchi
  • Satoshi Tsuneda
  • Naohiro Noda
  • 全て表示

16
8
開始ページ
18439
終了ページ
18453
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/ijms160818439
出版者・発行元
MDPI AG

Hepatitis C virus (HCV) is an important etiological agent of severe liver diseases, including cirrhosis and hepatocellular carcinoma. The HCV genome encodes nonstructural protein 3 (NS3) helicase, which is a potential anti-HCV drug target because its enzymatic activity is essential for viral replication. Some anthracyclines are known to be NS3 helicase inhibitors and have a hydroxyanthraquinone moiety in their structures; mitoxantrone, a hydroxyanthraquinone analogue, is also known to inhibit NS3 helicase. Therefore, we hypothesized that the hydroxyanthraquinone moiety alone could also inhibit NS3 helicase. Here, we performed a structure-activity relationship study on a series of hydroxyanthraquinones by using a fluorescence-based helicase assay. Hydroxyanthraquinones inhibited NS3 helicase with IC50 values in the micromolar range. The inhibitory activity varied depending on the number and position of the phenolic hydroxyl groups, and among different hydroxyanthraquinones examined, 1,4,5,8-tetrahydroxyanthraquinone strongly inhibited NS3 helicase with an IC50 value of 6 mu M. Furthermore, hypericin and sennidin A, which both have two hydroxyanthraquinone-like moieties, were found to exert even stronger inhibition with IC50 values of 3 and 0.8 mu M, respectively. These results indicate that the hydroxyanthraquinone moiety can inhibit NS3 helicase and suggest that several key chemical structures are important for the inhibition.

リンク情報
DOI
https://doi.org/10.3390/ijms160818439
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26262613
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000366826100092&DestApp=WOS_CPL
ID情報
  • DOI : 10.3390/ijms160818439
  • ISSN : 1422-0067
  • PubMed ID : 26262613
  • Web of Science ID : WOS:000366826100092

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