title: In vitro and in vivo evaluation of a novel antiherpetic flavonoid, 4'-phenylflavone, and its synergistic actions with acyclovir.
abstract: The development of therapeutic agents for preventing herpes simplex virus (HSV) infections has become urgently necessary because of the increasing incidence of this virus and its role as a cofactor in the transmission of human immunodeficiency virus infection. We have evaluated the antiviral activities of a series of natural and synthetic flavonoids and found that a synthetic flavonoid, 4'-phenylflavone, showed the highest activity against acyclovir (ACV)-sensitive and ACV-resistant strains of HSV-1, as well as HSV-2, with a selectivity index of 213, 35 and 55, respectively. Although the attachment and penetration of HSV-1 to host cells and the synthesis of viral proteins were not inhibited, the infectivity of the virus and the amount of progeny virus released were reduced by 4'-phenylflavone treatment in a dose-dependent manner. 4'-Phenylflavone plus ACV synergistically inhibited the replication of HSV-1. This flavonoid also showed efficacy in vivo and potentiated the antiherpetic effect of ACV in a mouse model of genital herpes. Our results suggest that 4'-phenylflavone might be useful as a candidate for the development of novel antiherpetic therapeutics.
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. khayashi@pha.u-toyama.ac.jp
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Munekazu
authors.initials: M
authors.lastname: Iinuma
authors.forename: Kohei
authors.initials: K
authors.lastname: Sasaki
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D000212:Acyclovir / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002460:Cell Line; D004357:Drug Synergism; D005260:Female; D047309:Flavones / Q000502:physiology* / Q000627:therapeutic use; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D018139:Simplexvirus / Q000187:drug effects* / Q000502:physiology; D053586:Virus Internalization / Q000187:drug effects; D057074:Virus Release / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: C575660:4'-phenylflavone; D047309:Flavones; D000212:Acyclovir