Synthesis and antiviral effects of isosteviol-derived analogues against the hepatitis B virus

Tsurng Juhn Huang, Bo Hon Chou, Cheng Wen Lin, Jen Hsien Weng, Chang Hung Chou, Li Ming Yang, Shwu Jiuan Lin

研究成果: 雜誌貢獻文章同行評審

18 引文 斯高帕斯(Scopus)

摘要

Among several isosteviol-derived analogues, NC-8 (ent-16-oxobeyeran-19-N- methylureido) showed inhibitory potency against the hepatitis B virus (HBV) in HepG2 2.2.15 cells. Its anti-HBV mechanism was then next investigated in a human hepatoma cell culture system. Results showed that it specifically inhibited viral gene expression and reduced the level of encapsidated viral DNA intermediates in Huh7 cells that expressed replicating HBV. It also potently attenuated all viral promoter activity in HBV-expressing Huh7 cells, but not in cells lacking HBV expression. By examining its antiviral mechanism in cellular signaling pathways, NC-8 was found to inhibit the activity of the nuclear factor (NF)-κB element-containing promoter, but only slightly enhanced activities of activator protein (AP)-1- and interferon-sensitive response element (ISRE)-containing promoters in HBV-expressing cells. NC-8 also significantly eliminated NF-κB (p65/p50) and Toll-like receptor (TLR)2 proteins, but increased the IκBα protein level in a dose-dependent manner in HBV-transfected Huh7 cells, while these protein levels were apparently unchanged in non-transfected cells. Meanwhile, NC-8-treated nuclear extracts that co-expressed HBV inhibited the binding of NF-κB to the CS1 site of HBV major surface gene and specifically attenuated CS1-containing promoter activity. Taken together, this study suggests that the antiviral mechanism of NC-8 appears to be mediated by disturbing replication and gene expression of HBV and by inhibiting the host TLR2/NF-κB signaling pathway.

原文英語
頁(從 - 到)107-114
頁數8
期刊Phytochemistry
99
DOIs
出版狀態已發佈 - 三月 2014

ASJC Scopus subject areas

  • Plant Science
  • Biochemistry
  • Molecular Biology
  • Horticulture
  • Medicine(all)

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