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

被引：6

作者：

Brandi, Giorgio ^{[1
]}

Rossi, Luigia ^{[2
]}

Schiavano, Giuditta F. ^{[1
]}

Millo, Enrico ^{[3
,4
]}

Magnani, Mauro ^{[2
]}

机构：

[1] Univ Urbino Carlo Bo, Hyg Sect, Dept Biomol Sci, I-61029 Urbino, PU, Italy

[2] Univ Urbino Carlo Bo, Dept Biomol Sci, Biochem & Mol Biol Sect, I-61029 Urbino, PU, Italy

[3] Univ Genoa, Dept Expt Med, Biochem Sect, I-16132 Genoa, Italy

[4] Univ Genoa, Ctr Excellence Biomed Res, I-16132 Genoa, Italy

来源：

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS | 2009年 / 34卷 / 02期

关键词：

Antiviral prodrug; Aciclovir homodimer; Anti-HSV-1; activity; HERPES-SIMPLEX-VIRUS; STRATEGIES;

D O I：

10.1016/j.ijantimicag.2009.02.025

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

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 mu M vs. 6.6 mu M for ACV] and was non-toxic in the cells at concentrations <= 15 mu M. 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. (C) 2009 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.

引用

页码：177 / 180

页数：4

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