title: Novel 4-thiazolidinones as non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA polymerase.
abstract: In continuation of our efforts to develop new derivatives as hepatitis C virus (HCV) NS5B inhibitors, we synthesized novel 5-arylidene-4-thiazolidinones. The novel compounds 29-42, together with their synthetic precursors 22-28, were tested for HCV NS5B inhibitory activity; 12 of these compounds displayed IC50 values between 25.3 and 54.1 µM. Compound 33, an arylidene derivative, was found to be the most active compound in this series with an IC50 value of 25.3 µM. Molecular docking studies were performed on the thumb pocket-II of NS5B to postulate the binding mode for these compounds.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Marmara University, Haydarpaşa, İstanbul, Turkey.
authors.forename: Gizem
authors.initials: G
authors.lastname: Çakir
authors.forename: İlkay
authors.initials: İ
authors.lastname: Küçükgüzel
authors.forename: Rupa
authors.initials: R
authors.lastname: Guhamazumder
authors.forename: Esra
authors.initials: E
authors.lastname: Tatar
authors.forename: Dinesh
authors.initials: D
authors.lastname: Manvar
authors.forename: Amartya
authors.initials: A
authors.lastname: Basu
authors.forename: Bhargav A
authors.initials: BA
authors.lastname: Patel
authors.forename: Javairia
authors.initials: J
authors.lastname: Zia
authors.forename: Tanaji T
authors.initials: TT
authors.lastname: Talele
authors.forename: Neerja
authors.initials: N
authors.lastname: Kaushik-Basu
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D017076:Computer-Aided Design; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D057166:High-Throughput Screening Assays; D006801:Humans; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053778:Thiazolidines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: 4-Thiazolidinones; Antiviral agents; HCV NS5B polymerase; Hepatitis C; Molecular modeling