title: Effects of the aryl linker and the aromatic substituent on the anti-HCV activities of aryl diketoacid (ADK) analogues.
abstract: Based on our pharmacophore model of the aryl diketoacids (ADKs), we designed and prepared a series of novel ADK analogues, which showed potent inhibitory activities against the NS5B polymerase in the submicromolar range. Pharmacophore-guided docking study revealed that the antiviral activities of the ADKs are highly dependent upon the aryl linker as well as the size and position of the aromatic substituent. It is of another importance that, unlike previously reported ADKs, three ADK analogues synthesized in this study effectively blocked Hepatitis C Virus (HCV) replication in the replicon systems.
authors.affiliation: Department of Bioscience & Biotechnology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Ki-Sun
authors.initials: KS
authors.lastname: Kim
authors.forename: Hyo Seon
authors.initials: HS
authors.lastname: Lee
authors.forename: Kwang-Su
authors.initials: KS
authors.lastname: Park
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.forename: Seock-Yong
authors.initials: SY
authors.lastname: Kang
authors.forename: Soo Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hyung Soon
authors.initials: HS
authors.lastname: Park
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Kim
authors.forename: Youhoon
authors.initials: Y
authors.lastname: Chong
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D016174:Hepacivirus / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007651:Keto Acids / Q000737:chemistry* / Q000494:pharmacology*; D008956:Models, Chemical; D008968:Molecular Conformation; D011485:Protein Binding; D012093:Replicon / Q000187:drug effects; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D007651:Keto Acids; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase