Phenoxazine derivatives suppress the infections caused by herpes simplex virus type-1 and herpes simplex virus type-2 intravaginally inoculated into mice. 2010

Kyoko Hayashi, and Toshimitsu Hayashi, and Keisuke Miyazawa, and Akio Tomoda
Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Japan.

We examined the in vivo antiviral activities of 2-amino-4,4α-dihydro-4α-7-dimethyl-3H-phenoxazine-3-one (Phx-1), 3-amino-1,4α-dihydro-4α-8-dimethyl-2H-phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3-one (Phx-3) against herpes viruses. The virus yield three days after administration, changes in the 6-degree's lesion scores, and the morbidity were assessed after herpes simplex virus type-1 (HSV-1) [acyclovir (ACV)-sensitive KOS strain or ACV-resistant A4-3 strain] or HSV-2 (ACV-sensitive UW 268 strain) was inoculated intravaginally to mice with administration of Phx-1, Phx-2, Phx-3, or ACV (0.2 mg per administration, 3 times daily) for 8 days starting from 1 day before virus inoculation to 7 days after infection. Phx-1, Phx-2, and Phx-3 extensively suppressed the virus yield of HSV-1. Only Phx-2 exerted moderate inhibitory effects against HSV-2 in mice. The lesion scores, as clinical signs manifested by infection of the KOS strain of HSV-1, were extensively suppressed by intravaginal application of Phx-1, Phx-2, or Phx-3. The lesion scores in HSV-2-infected mice indicated moderate suppression, when Phx-1, Phx-2, or Phx-3 was applied. Without treatment by one of the compounds, none of the HSV-1-infected mice died, but all the HSV-2-infected ones did. However, by the administration of Phx-1, Phx-2, or Phx-3 fairly improved the survival rates of the HSV-2-infected mice. Phx-2 showed dose-dependent anti-HSV-2 efficacy when administered at doses of 0.2 and 1 mg per administration. The present in vivo data suggest that the Phx-1, Phx-2, and Phx-3 are attractive candidates for agents to prevent both replication of HSV and aggravation of lesions caused by these viruses.

UI MeSH Term Description Entries
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D010078 Oxazines Six-membered heterocycles containing an oxygen and a nitrogen.
D002522 Chlorocebus aethiops A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research. African Green Monkey,Cercopithecus aethiops,Cercopithecus griseoviridis,Cercopithecus griseus,Cercopithecus pygerythrus,Cercopithecus sabeus,Cercopithecus tantalus,Chlorocebus cynosuros,Chlorocebus cynosurus,Chlorocebus pygerythrus,Green Monkey,Grivet Monkey,Lasiopyga weidholzi,Malbrouck,Malbrouck Monkey,Monkey, African Green,Monkey, Green,Monkey, Grivet,Monkey, Vervet,Savanah Monkey,Vervet Monkey,Savannah Monkey,African Green Monkey,Chlorocebus cynosuro,Green Monkey, African,Green Monkeys,Grivet Monkeys,Malbrouck Monkeys,Malbroucks,Monkey, Malbrouck,Monkey, Savanah,Monkey, Savannah,Savannah Monkeys,Vervet Monkeys
D005260 Female Females
D006558 Herpes Genitalis Infection of the genitals (GENITALIA) with HERPES SIMPLEX VIRUS in either the males or the females. Genital Herpes,Herpes Simplex, Genital,Herpes Simplex Virus Genital Infection,Genital Herpes Simplex,Herpes, Genital
D006561 Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. (Dorland, 27th ed.) Herpes Simplex Virus Infection
D000282 Administration, Intravaginal The insertion of drugs into the vagina to treat local infections, neoplasms, or to induce labor. The dosage forms may include medicated pessaries, irrigation fluids, and suppositories. Administration, Vaginal,Drug Administration, Vaginal,Instillation, Vaginal,Intravaginal Administration,Vaginal Drug Administration,Vaginal Administration,Administration, Vaginal Drug,Administrations, Intravaginal,Administrations, Vaginal,Administrations, Vaginal Drug,Drug Administrations, Vaginal,Instillations, Vaginal,Intravaginal Administrations,Vaginal Administrations,Vaginal Drug Administrations,Vaginal Instillation,Vaginal Instillations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D014709 Vero Cells A CELL LINE derived from the kidney of the African green (vervet) monkey, (CHLOROCEBUS AETHIOPS) used primarily in virus replication studies and plaque assays. Cell, Vero,Cells, Vero,Vero Cell

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