title: Investigation into the mode of action of R-91650, an arylpiperazinyl fluoroquinolone, on feline immunodeficiency virus replication inhibitory activity.
abstract: The mode of action of R-91650, an arylpiperazinyl fluoroquinolone, on feline immunodeficiency virus (FIV) replication inhibitory activity was investigated. R-91650 inhibited replication of FIV at non-cytotoxic concentration levels in both acutely infected peripheral blood mononuclear cells and chronically infected P-CrFK cells. The compound reduced the intracellular p24 concentration levels in P-CrFK cells in a dose-dependent manner. Northern blot analysis revealed that R-91650 selectively prevented the accumulation of FIV mRNA in P-CrFK cells. However, the compound did not inhibit FIV-long terminal repeat (LTR) promoter activity in the reporter gene expression analysis. These data suggest that R-91650 is a novel inhibitor of FIV replication that inhibits a certain step or steps following transcription initiation of the FIV-LTR promoter.
authors.affiliation: Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kashiwase
authors.forename: T
authors.initials: T
authors.lastname: Katsube
authors.forename: K
authors.initials: K
authors.lastname: Iida
authors.forename: T
authors.initials: T
authors.lastname: Komai
authors.forename: T
authors.initials: T
authors.lastname: Nishigaki
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D002415:Cats; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D015683:Gene Products, gag / Q000096:biosynthesis; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D020079:Terminal Repeat Sequences / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: C410823:1-ethyl-8-difluoromethoxy-6-fluoro-4-oxo-(4-pyrimidinylpiperazine-1-yl)-1,4-dihydroquinoline-3-carboxylic acid; D000998:Antiviral Agents; D017931:DNA Primers; D015683:Gene Products, gag; D010879:Piperazines; D011804:Quinolines; D012333:RNA, Messenger; D012367:RNA, Viral; C074662:p24 protein, Feline immunodeficiency virus