Hu J M, Hsiung G D
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Antimicrob Agents Chemother. 1989 Sep;33(9):1600-5. doi: 10.1128/AAC.33.9.1600.
Two new antiviral agents, compound 164, also known as 2'-nor-cGMP (9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]-guani ne P-oxide), and compound 102 [4-amino-5-bromo-7-(2-hydroxyethoxymethyl)-pyrrolo(2,3-d)pyrimidine], together with acyclovir for comparison, were evaluated for activities against the guinea pig lymphotropic herpesvirus infection in vitro by plaque reduction and virus yield reduction assays in guinea pig embryo cells. The two new compounds were demonstrated to be more potent against guinea pig lymphotropic herpesvirus infections than acyclovir. Compound 164 was the most potent of the three; drug concentrations required to reduce the number of plaques by 50% were 2, 35.5, and 144.5 microM for compounds 164, 102, and acyclovir, respectively. The two new compounds were cytostatic but not cytotoxic to guinea pig embryo cells in cultures. Attempts were made to investigate the inhibition of viral replication by these compounds, and the influence of test conditions on antiviral evaluations is discussed.
两种新型抗病毒剂,即化合物164(也称为2'-去甲-cGMP,9-[(2-羟基-1,3,2-二氧磷杂环己烷-5-基)氧甲基]-鸟嘌呤P-氧化物)和化合物102 [4-氨基-5-溴-7-(2-羟基乙氧基甲基)-吡咯并(2,3-d)嘧啶],与阿昔洛韦作为对照,通过在豚鼠胚胎细胞中进行蚀斑减少试验和病毒产量减少试验,在体外评估了它们对豚鼠嗜淋巴细胞性疱疹病毒感染的活性。结果表明,这两种新型化合物对豚鼠嗜淋巴细胞性疱疹病毒感染的效力比阿昔洛韦更强。化合物164是三者中效力最强的;使蚀斑数量减少50%所需的药物浓度,化合物164、102和阿昔洛韦分别为2、35.5和144.5 microM。这两种新型化合物在培养物中对豚鼠胚胎细胞具有细胞生长抑制作用,但无细胞毒性。已尝试研究这些化合物对病毒复制的抑制作用,并讨论了试验条件对抗病毒评估的影响。