Evaluation of inhibitory effects of thiobarbituric acid derivatives targeting HCV NS5B polymerase.
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 compound's 12.3 microM value. CC(50) was higher than 77 microM for all compounds tested, suggesting that they are useful candidates for anti-HCV therapy.
Lee
Jong-Ho
JH
Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In 449-791, Korea.
Lee
Sangyoon
S
Park
Mi Young
MY
Ha
Hyun-Joon
HJ
Myung
Heejoon
H
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D005562:Formazans / Q000737:chemistry; D016174:Hepacivirus / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D013778:Tetrazolium Salts / Q000737:chemistry; D013858:Thiobarbiturates / Q000138:chemical synthesis / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D005562:Formazans; D013778:Tetrazolium Salts; D013858:Thiobarbiturates; D017361:Viral Nonstructural Proteins; C079782:MTT formazan; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase