title: Shape-based virtual screening, synthesis and evaluation of novel pyrrolone derivatives as antiviral agents against HCV.
abstract: A ligand-based approach was applied to screen in silico a library of commercially available compounds, with the aim to find novel inhibitors of the HCV replication starting from the study of the viral NS3 helicase. Six structures were selected for evaluation in the HCV subgenomic replicon assay and one hit was found to inhibit the HCV replicon replication in the low micromolar range. A small series of new pyrrolone compounds was designed and synthesised, and novel structures were identified with improved antiviral activity.
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, King Edward VII Avenue, Cardiff CF103NB, UK. Electronic address: bassettom@cardiff.ac.uk.
authors.forename: Marcella
authors.initials: M
authors.lastname: Bassetto
authors.affiliation: Rega Institute for Medical Research, University of Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: Rega Institute for Medical Research, University of Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: Department of Chemistry & Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Yerukhimovich
authors.affiliation: Department of Chemistry & Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
authors.forename: David N
authors.initials: DN
authors.lastname: Frick
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, King Edward VII Avenue, Cardiff CF103NB, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancale
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011758:Pyrroles
keywords: Anti-HCV activity; Ligand-based virtual screening; Novel pyrrolones; Shape-similarity search