title: Characterization of thiobarbituric acid derivatives as inhibitors of hepatitis C virus NS5B polymerase.
abstract: In an effort to find chemicals inhibiting the enzymatic activity of the hepatitis C virus (HCV) NS5B polymerase, a series of thiobarbituric acid derivatives were selected from a library provided by Korea Research Institute of Chemical Technology and characterized. The selected compounds exhibited IC50 values ranging from 1.7 to 3.8 μM, and EC50 values ranging from 12.3 to 20.7 μM against NS5B polymerase of type 1b strain. They showed little effect against type 2a polymerase. One of the compounds, G05, was selected and further characterized. It inhibited the synthesis of RNA by recombinant HCV NS5B polymerase in a dose dependent manner. The CC50 value was 77 μM. The inhibition was in a noncompetitive manner with the substrate UTP. The compound did not inhibit the elongation step of RNA synthesis in a single-cycle processive polymerization assay. It inhibited the binding of NS5B polymerase to the template RNA in a dose-dependent manner.
authors.affiliation: Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, Gyung-Gi Do 449-791, Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Sangyoon
authors.initials: S
authors.lastname: Lee
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Park
authors.forename: Heejoon
authors.initials: H
authors.lastname: Myung
mesh_terms: D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D007723:Korea; D012367:RNA, Viral / Q000378:metabolism; D013329:Structure-Activity Relationship; D013858:Thiobarbiturates / Q000737:chemistry* / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D004791:Enzyme Inhibitors; D012367:RNA, Viral; D013858:Thiobarbiturates; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C029684:thiobarbituric acid