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

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. ©2010 the japanese pharmacological society.