一种作为前药的阿昔洛韦新型同型二聚体，具有更高的溶解度和抗病毒活性。

A new homodimer of aciclovir as a prodrug with increased solubility and antiviral activity.

作者信息

Brandi Giorgio, Rossi Luigia, Schiavano Giuditta F, Millo Enrico, Magnani Mauro

机构信息

Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.

出版信息

Int J Antimicrob Agents. 2009 Aug;34(2):177-80. doi: 10.1016/j.ijantimicag.2009.02.025. Epub 2009 Apr 24.

DOI:10.1016/j.ijantimicag.2009.02.025

PMID:19394201

Abstract

Aciclovir (ACV) is the drug of choice against herpes simplex virus type 1 (HSV-1) infection. However, its limited solubility in water and limited oral bioavailability represent the main limitations of this drug. Utilising a plaque reduction assay, this study assessed the antiherpetic activity of a new homodimer of ACV (ACVp(2)ACV) with a higher water solubility. ACVp(2)ACV markedly inhibited HSV-1 replication in Vero cells [50% effective concentration (EC(50)) of 2.8 microM vs. 6.6 microM for ACV] and was non-toxic in the cells at concentrations <or= 15 microM. ACVp(2)ACV encapsulated in erythrocytes provides effective protection against HSV-1 replication in human macrophages and also partially against the HSV-1 thymidine kinase-deficient strain. Thus, ACVp(2)ACV acts as an effective antiviral prodrug against HSV-1.

摘要

阿昔洛韦（ACV）是对抗1型单纯疱疹病毒（HSV-1）感染的首选药物。然而，其在水中的溶解度有限以及口服生物利用度有限是该药物的主要局限性。本研究利用蚀斑减少试验评估了一种具有更高水溶性的新型阿昔洛韦同型二聚体（ACVp(2)ACV）的抗疱疹活性。ACVp(2)ACV显著抑制Vero细胞中的HSV-1复制[50%有效浓度（EC(50)）为2.8微摩尔，而阿昔洛韦为6.6微摩尔]，并且在浓度≤15微摩尔时对细胞无毒害作用。包裹在红细胞中的ACVp(2)ACV可有效保护人类巨噬细胞免受HSV-1复制的影响，并且对HSV-1胸苷激酶缺陷株也有部分保护作用。因此，ACVp(2)ACV作为一种针对HSV-1的有效抗病毒前药发挥作用。