title: 2,6-Bis-arylmethyloxy-5-hydroxychromones with antiviral activity against both hepatitis C virus (HCV) and SARS-associated coronavirus (SCV).
abstract: In this study, as a bioisosteric alternative scaffold of the antiviral aryl diketoacids (ADKs), we used 5-hydroxychromone on which two arylmethyloxy substituents were installed. The 5-hydroxychromones (5b-5g) thus prepared showed anti-HCV activity and, depending on the aromatic substituents on the 2-arylmethyloxy moiety, some of the derivatives (5b-5f) were also active against SCV. In addition, unlike the ADKs which showed selective inhibition against the helicase activity of the SCV NTPase/helicase, the 5-hydroxychromones (5b-5f) were active against both NTPase and helicase activities of the target enzyme. Among those, 3-iodobenzyloxy-substituted derivative 5e showed the most potent activity against HCV (EC(50) = 4 μM) as well as SCV (IC(50) = 4 μM for ATPase activity, 11 μM for helicase activity) and this might be used as a platform structure for future development of the multi-target or broad-spectrum antivirals.
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Yu
authors.forename: Hye Ri
authors.initials: HR
authors.lastname: Park
authors.forename: Kyung Bo
authors.initials: KB
authors.lastname: Kim
authors.forename: Chaewoon
authors.initials: C
authors.lastname: Lee
authors.forename: Suh Young
authors.initials: SY
authors.lastname: Cho
authors.forename: Jihoon
authors.initials: J
authors.lastname: Kang
authors.forename: Hyunjun
authors.initials: H
authors.lastname: Yoon
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Kim
authors.forename: Hyunah
authors.initials: H
authors.lastname: Choo
authors.forename: Yong-Joo
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Youhoon
authors.initials: Y
authors.lastname: Chong
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D002867:Chromones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D002867:Chromones