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新型无环腺苷类似物可抑制爱泼斯坦-巴尔病毒复制。

Novel acyclic adenosine analogs inhibit Epstein-Barr virus replication.

作者信息

Lin J C, DeClercq E, Pagano J S

机构信息

Lineberger Cancer Research Center, School of Medicine, University of North Carolina Chapel Hill 27514.

出版信息

Antimicrob Agents Chemother. 1987 Sep;31(9):1431-3. doi: 10.1128/AAC.31.9.1431.

Abstract

The effect of three new acyclic adenosine analogs, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)adenine (PMEA), and (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA], on Epstein-Barr virus (EBV) replication was studied. Both (S)-HPMPA and PMEA but not (S)-DHPA effectively inhibited EBV DNA replication in virus-producer P3HR-1 cells and in latently infected Raji cells superinfected with P3HR-1 virus, as determined by cRNA-DNA hybridization and density gradient centrifugation. The 50% effective doses for inhibiting virus replication were 0.08 and 1.1 microM for (S)-HPMPA and PMEA, respectively. Both drugs were cytostatic but not cytotoxic to the cells at a concentration as high as 100 microM. These results indicate that (S)-HPMPA and PMEA are potent and selective anti-EBV agents in vitro.

摘要

研究了三种新型无环腺苷类似物,即(S)-9-(3-羟基-2-膦酰甲氧基丙基)腺嘌呤[(S)-HPMPA]、9-(2-膦酰甲氧基乙基)腺嘌呤(PMEA)和(S)-9-(2,3-二羟基丙基)腺嘌呤[(S)-DHPA]对爱泼斯坦-巴尔病毒(EBV)复制的影响。通过cRNA-DNA杂交和密度梯度离心法测定,(S)-HPMPA和PMEA均能有效抑制病毒产生细胞P3HR-1及被P3HR-1病毒超感染的潜伏感染细胞Raji中的EBV DNA复制,但(S)-DHPA无此作用。(S)-HPMPA和PMEA抑制病毒复制的50%有效剂量分别为0.08和1.1 microM。两种药物在高达100 microM的浓度下对细胞具有细胞生长抑制作用,但无细胞毒性。这些结果表明,(S)-HPMPA和PMEA在体外是有效的选择性抗EBV药物。

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