Characterization of thiobarbituric acid derivatives as inhibitors of hepatitis C virus NS5B polymerase
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چکیده
منابع مشابه
New Pyrazolobenzothiazine Derivatives as Hepatitis C Virus NS5B Polymerase Palm Site I Inhibitors
We have previously identified the pyrazolobenzothiazine scaffold as a promising chemotype against hepatitis C virus (HCV) NS5B polymerase, a validated and promising anti-HCV target. Herein we describe the design, synthesis, enzymatic, and cellular characterization of new pyrazolobenzothiazines as anti-HCV inhibitors. The binding site for a representative derivative was mapped to NS5B palm site ...
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A series of thiobarbituric acid derivatives were constructed and evaluated for inhibitory activity on hepatitis C virus NS5B polymerase. In biochemical assays using purified viral polymerase and RNA template, the IC(50) value was improved to 0.41 microM from the original compound's 1.7 microM value. In HCV subgenomic replicon assay, the EC(50) value was improved to 3.7 microM from the original ...
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HCV (Hepatitis C virus) that causes chronic liver disease. HCV NS5B RNA-dependent RNA polymerase (RbRp) and NS3 protease are able to affect virtual replication of genes. Computer-aided drug design (CADD) aims at designing new molecules with pharmacological activity. In this study, we used the Discovery Studio 2.0 program and the scoring function to estimate the Dock Score, piecewise linear pote...
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More than 20 years after the identification of the hepatitis C virus (HCV) as a novel human pathogen, the only approved treatment remains a combination of pegylated interferon-α and ribavirin. This rather non-specific therapy is associated with severe side effects and by far not everyone benefits from treatment. Recently, progress has been made in the development of specifically targeted antivi...
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In a quest to identify novel compounds targeting HCV viral replicase, we evaluated a new series of 4-thiazolidinone derivatives (18 compounds). Our in vitro NS5B RdRp inhibition analysis with a series of 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid (2-(5-nitro-2-furyl/substituted phenyl)-4-thiazolidinone-3-yl) amides (1-7) yielded IC50 values ranging between 45-75 microM. Of these, lead c...
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ژورنال
عنوان ژورنال: Virology Journal
سال: 2011
ISSN: 1743-422X
DOI: 10.1186/1743-422x-8-18