title: Molecular design, synthesis and cell based HCV replicon assay of novel benzoxazole derivatives.
abstract: Hepatitis C virus inhibitors based on benzoxazole scaﬀold were designed based on molecular modeling simulation study including docking into the NS5B polymerase active site. Several compounds showed significant high simulation docking scores relative to the assigned benzimidazole lead compound. The designed compounds were synthesized, structurally elucidated and their antiviral activity was evaluated through cell-based replicon in cultured Huh 5-2 cells. A number of the synthesized compounds showed significant inhibitory activity ranging from (52.2% inhibition up to 98% at<50 µg/mL). N-Benzyl-2-phenylbenzo[1,3]oxazole-5-carboxamide (8b) and N-Phenethyl-2-phenylbenzo[1,3] oxazole-5-carboxamide (8c) demonstrated genuine HCV inhibitory activity with EC50 values of 41.6 and 24.5 µg/mL respectively.
authors: Pharmaceutical Chemistry Department, Faculty of Pharmacy Ain Shams University, Cairo, Egypt.
authors: M A H
authors: MA
authors: Ismail
authors: M
authors: M
authors: Adel
authors: N S M
authors: NS
authors: Ismail
authors: K A M
authors: KA
authors: Abouzid
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D001583:Benzoxazoles; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase