Effects of the aryl linker and the aromatic substituent on the anti-HCV activities of aryl diketoacid (ADK) analogues.
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.
Kim
Jinyoung
J
Department of Bioscience & Biotechnology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Kim
Ki-Sun
KS
Lee
Hyo Seon
HS
Park
Kwang-Su
KS
Park
Sun Young
SY
Kang
Seock-Yong
SY
Lee
Soo Jae
SJ
Park
Hyung Soon
HS
Kim
Dong-Eun
DE
Chong
Youhoon
Y
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
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