Atsuya, Yamashita and Yuusuke, Fujimoto and Mayumi, Tamaki and Andi, Setiawan and Tomohisa, Tanaka and Kaori, Okuyama-Dobashi and Hirotake, Kasai and Koichi, Watashi and Takaji, Wakita and Masaaki, Toyama and Masanori, Baba and Nicole, J. de Voogd and Shinya, Maekawa and Nobuyuki, Enomoto and Junichi, Tanaka and Kohji, Moriishi (2015) Identification of Antiviral Agents Targeting Hepatitis B Virus Promoter from Extracts of Indonesian Marine Organisms by a Novel Cell-Based Screening Assay. Mar. Drugs, 13 (1). pp. 6759-6773. ISSN 1660-3397


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The current treatments of chronic hepatitis B (CHB) face a limited choice of vaccine, antibody and antiviral agents. The development of additional antiviral agents is still needed for improvement of CHB therapy. In this study, we established a screening system in order to identify compounds inhibiting the core promoter activity of hepatitis B virus (HBV). We prepared 80 extracts of marine organisms from the coral reefs of Indonesia and screened them by using this system. Eventually, two extracts showed high inhibitory activity (>95%) and low cytotoxicity (66% to 77%). Solvent fractionation, column chromatography and NMR analysis revealed that 3,5-dibromo-2-(2,4-dibromophenoxy)-phenol (compound 1) and 3,4,5-tribromo-2-(2,4-dibromophenoxy)-phenol (compound 2), which are classified as polybrominated diphenyl ethers (PBDEs), were identified as anti-HBV agents in the extracts. Compounds 1 and 2 inhibited HBV core promoter activity as well as HBV production from HepG2.2.15.7 cells in a dose-dependent manner. The EC50 values of compounds 1 and 2 were 0.23 and 0.80 µM, respectively, while selectivity indexes of compound 1 and 2 were 18.2 and 12.8, respectively. These results suggest that our cell-based HBV core promoter assay system is useful to determine anti-HBV compounds, and that two PBDE compounds are expected to be candidates of lead compounds for the development of anti-HBV drugs.

Item Type: Article
Subjects: Q Science > Q Science (General)
Depositing User: Prof Andi Setiawan
Date Deposited: 03 Nov 2021 09:27
Last Modified: 03 Nov 2021 09:27

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