膦酰甲氧基烷基嘌呤和嘧啶衍生物对兔TK+和TK -单纯疱疹病毒1型角膜炎的影响。

Effects of phosphonylmethoxyalkyl-purine and -pyrimidine derivatives on TK+ and TK- HSV-1 keratitis in rabbits.

作者信息

Maudgal P C, De Clercq E

机构信息

Eye Research Laboratory, Ophthalmology Clinic, Leuven, Belgium.

出版信息

Antiviral Res. 1991 Jul;16(1):93-100. doi: 10.1016/0166-3542(91)90061-u.

DOI:10.1016/0166-3542(91)90061-u

PMID:1663731

Abstract

The phosphonylmethoxyalkyl derivatives HPMPA [(S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine], HPMPC [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] and PMEA [9-(2-phosphonylmethoxyethyl)adenine] were evaluated as 0.2% eyedrops for their efficacy in the treatment of experimental herpes simplex virus type 1 (HSV-1) keratitis in the rabbit model. BVDU 0.2% eyedrops were used as the reference treatment. HPMPA, HPMPC, PMEA and BVDU eyedrops showed a rapid and highly significant healing effect (P less than 0.005) on keratitis caused by TK+ HSV-1 (McIntyre strain) when compared with placebo eyedrops, whereas BVDU treatment did not affect the course of TK- HSV-1 (VMW-1837) keratitis. HPMPA and HPMPC treatment again caused a highly significant healing (P less than 0.005, compared with placebo eyedrops). Although PMEA eyedrops were less effective than HPMPA or HPMPC eyedrops, the effect of PMEA eyedrops was significantly (P less than 0.05) different from the effect of either BVDU or placebo eyedrops.

摘要

对磷酰甲氧基烷基衍生物HPMPA [（S）-9-（3-羟基-2-磷酰甲氧基丙基）腺嘌呤]、HPMPC [（S）-1-（3-羟基-2-磷酰甲氧基丙基）胞嘧啶]和PMEA [9-（2-磷酰甲氧基乙基）腺嘌呤]制成0.2%的眼药水，在兔模型中评估其治疗实验性单纯疱疹病毒1型（HSV-1）角膜炎的疗效。将0.2%的BVDU眼药水用作对照治疗。与安慰剂眼药水相比，HPMPA、HPMPC、PMEA和BVDU眼药水对由TK + HSV-1（麦金太尔毒株）引起的角膜炎显示出快速且高度显著的愈合效果（P < 0.005），而BVDU治疗对TK - HSV-1（VMW-1837）角膜炎的病程没有影响。HPMPA和HPMPC治疗再次引起高度显著的愈合（与安慰剂眼药水相比，P < 0.005）。尽管PMEA眼药水的效果不如HPMPA或HPMPC眼药水，但PMEA眼药水的效果与BVDU或安慰剂眼药水的效果有显著差异（P < 0.05）。