Dendrimers, a new class of candidate topical microbicides with activity against herpes simplex virus infection
Dendrimers, a new class of candidate topical microbicides with activity against herpes simplex virus infection
复制标题
DOI：
10.1128/aac.44.9.2471-2474.2000
复制
发表时间：
2000-09-01
影响因子：
4.9
通讯作者：
Bernstein, DI
中科院分区：
文献类型：
--
作者：
Bourne, N;Stanberry, LR;Bernstein, DI
树枝状聚合物是由多官能核合成的高度支化的大分子。它们已显示出多种生物学特性，包括在某些情况下的抗病毒活性。在这项研究中，五个树枝状聚合物进行了评估，在体外活性对单纯疱疹病毒（HSV）的I型和2型的细胞病变效应（CPE）抑制和空斑减少（PR）测定在人包皮成纤维细胞。在CPE抑制测定中，所有化合物对两种病毒类型都有活性，其中在加入病毒之前将药物加入细胞中。在PR试验中，抗病毒活性降低或丧失，其中细胞在加入药物之前与病毒一起孵育。预防效果表明，树枝状聚合物可能具有作为局部杀微生物剂的潜力，该产品旨在应用于阴道或直肠粘膜以防止性传播感染。评价了三种树枝状聚合物在小鼠中针对生殖器HSV感染的这种应用。两种化合物BRI-2999和BRI-6741在阴道内攻击前立即施用15 μ l 100-mg/ml溶液时显著降低感染率，并且最有效的化合物BRI-2999甚至在攻击前30分钟施用时也提供显著保护。这是第一次报告的微生物活性的树枝状聚合物在体内。
Dendrimers are large highly branched macromolecules synthesized from a polyfunctional core. They have shown a variety of biological properties, including, in some instances, antiviral activity. In this study, five dendrimers were evaluated for in vitro activity against herpes simplex virus (HSV) types I and 2 by cytopathic effect (CPE) inhibition and plaque reduction (PR) assay in human foreskin fibroblast cells. All of the compounds were active against both virus types in the CPE inhibition assay, in which drug was added to the cells prior to the addition of virus. Antiviral activity was reduced or lost in the PR assays, in which the cells were incubated with the virus before the drug was added. The prophylactic efficacy suggested that the dendrimers might have potential as topical microbicides, products intended to be applied to the vaginal or rectal mucosa to protect against sexually transmitted infections. Three dendrimers were evaluated for this application against genital HSV infection in mice. Two of the compounds, BRI-2999 and BRI-6741, significantly reduced infection rates when 15 mu l of a 100-mg/ml solution was administered immediately prior to intravaginal challenge, and the most effective compound, BRI-2999, provided significant protection even when applied 30 min before challenge. This is the first report of microbicidal activity by dendrimers in vivo.