title: Thujaplicin-copper chelates inhibit replication of human influenza viruses.
abstract: The effects of alpha-, beta- and gamma-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in Madin-Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 microM. These results indicate that the copper chelates inhibit influenza virus-induced apoptosis and that the inhibitory effects may be independent of influenza virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2 4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza virus-induced apoptosis. In this study, we demonstrated that thujaplicin-copper chelates inhibit influenza virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.
authors.affiliation: Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Miyamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kusagaya
authors.forename: N
authors.initials: N
authors.lastname: Endo
authors.forename: A
authors.initials: A
authors.lastname: Sometani
authors.forename: S
authors.initials: S
authors.lastname: Takeo
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Arima
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004285:Dogs; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D039821:Monoterpenes; D014334:Tropolone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C116333:2-hydroxy-5-isopropyl- 2,4,6-cycloheptatrienone; D000998:Antiviral Agents; D002614:Chelating Agents; D039821:Monoterpenes; D003300:Copper; D014334:Tropolone; C009479:beta-thujaplicin