Efficiency and selectivity of (E)-5-(2-bromovinyl)-2′-deoxyuridine and some other 5-substituted 2′-deoxypyrimidine nucleosides as anti-herpes agents

Reefschläger, J; Bärwolff, D.; Engelmann, Petra; Langen, P.; Rosenthal, H. A.

doi:10.1016/0166-3542(82)90025-0

Cited by 34 publications

(11 citation statements)

References 18 publications

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“…A wide variety of drugs have been tested for their antiviral effects on herpesviruses, particularly herpes simplex virus (2, 3, 7, 8, 13, 17-19, 22,23,25,26). Although these drugs have been shown to be most effective in limiting virus replication in vitro, they have also been shown to be at least partially effective in vivo under both experimental and natural conditions (9, 10, 13,14,17,20,31).…”

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confidence: 99%

Susceptibility of bovid herpesvirus 1 to antiviral drugs: in vitro versus in vivo efficacy of (E)-5-(2-Bromovinyl)-2'-deoxyuridine

Babiuk¹,

Acres²,

Misra³

et al. 1983

Antimicrob Agents Chemother

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The relative efficacies of a variety of antiviral drugs against bovid herpesvirus 1 was investigated. (E)-5-(2-Bromovinyl)-2'-deoxyuridine and trifluorothymidine were found to be inhibitory at doses of 0.01 ,ug/ml in in vitro yield reduction and plaque reduction assays. In contrast, acylovir was inactive even at concentrations as high as 1,000 ,ug/ml. Other drugs, including phosphonoformic acid, 9-0-Darabinofuranosyladenine, 5-iodo-2-deoxyuridine, and 1-3-D-arabinofuranosylcytosine were active at concentrations previously shown to inhibit herpes simplex virus. Oral administration of (E)-5-(2-bromovinyl)-2'-deoxyuridine to calves infected with bovid herpesvirus 1 had no effect on the level of virus shedding, clinical signs, or susceptibility to secondary bacterial infection with Pasteurella haemolytica. The reason for this lack of in vivo activity was that sufficient levels of the drug in blood were not achieved by oral administration.

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confidence: 99%

Susceptibility of bovid herpesvirus 1 to antiviral drugs: in vitro versus in vivo efficacy of (E)-5-(2-Bromovinyl)-2'-deoxyuridine

Babiuk¹,

Acres²,

Misra³

et al. 1983

Antimicrob Agents Chemother

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confidence: 99%

“…BVdU, therefore, should be relatively nontoxic for animal cells (1, 2). Minimal toxicity has been suggested by in vitro studies in which a number of mammalian cell lines were used (4,5,15), but there have been few studies of the effects of BVdU on human cell lines (20).To investigate the possible toxicity of BVdU for human cells, we studied its effect on the growth of human foreskin fibroblasts (HFF) and granulocyte-monocyte colony-forming cells (CFU-C) and its effect on the proliferation of stimulated peripheral blood mononuclear cells (PBM) (Fig. 1) …”

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confidence: 99%

Effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine on proliferation of human fibroblasts, peripheral blood mononuclear cells, and granulocyte-monocyte progenitor cells in vitro

Wittek¹,

Cohen²,

Arvin³

et al. 1983

Antimicrob Agents Chemother

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Inhibition of human fibroblasts, granulocyte-monocyte progenitor cells, and lymphocytes was observed at (E)-5-(2-bromovinyl)-2'-deoxyuridine concentrations ranging from 21 to 197 p.g/ml. These concentrations were 10-to 100-fold above usual serum concentrations after oral administration. (E)-5-(2-Bromovinyl)-2'-deoxyuridine compares favorably with currently used antivirals in terms of in vitro myelotoxicity and immunotoxicity.(E) -5 -(2-Bromovinyl)-2' -deoxyuridine (BVdU) is a synthetic pyrimidine deoxynucleoside which has demonstrated significant in vitro activity against herpes simplex virus type 1 and varicella-zoster virus (4,5).The drug has proven beneficial in herpesvirus infections in several animal models (4,6,7,11,16,18). In the only published human trial, oral BVdU limited the severity of herpes zoster in four patients, three of whom had underlying malignancy (3).The selective antiviral activity of BVdU is at least partially attributed to its phosphorylation by virus-induced thymidine kinase and its relatively low affinity for cellular phosphorylases. BVdU, therefore, should be relatively nontoxic for animal cells (1, 2). Minimal toxicity has been suggested by in vitro studies in which a number of mammalian cell lines were used (4,5,15), but there have been few studies of the effects of BVdU on human cell lines (20).To investigate the possible toxicity of BVdU for human cells, we studied its effect on the growth of human foreskin fibroblasts (HFF) and granulocyte-monocyte colony-forming cells (CFU-C) and its effect on the proliferation of stimulated peripheral blood mononuclear cells (PBM) (Fig. 1)

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“…22 In the original publication 22 the compound was erroneously assigned the 1-bromovinyl conformation. It was later identified as 5-(2-bromovinyl)-2 0 -deoxyuridine, 23 which makes that its superiority over other anti-HSV-1 agents was corroborated in a truly blinded fashion.…”

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confidence: 98%

The discovery of antiviral agents: Ten different compounds, ten different stories

Clercq

2008

Medicinal Research Reviews

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This review article, while autobiographical to some extent, describes the discovery of ten (classes of) antiviral compounds that have made (or just did not make) it to the market for the therapy of viral infections, but each in its own way influenced the landscape of our dealing with virus infections: (i) valaciclovir, (ii) BVDU, (iii) DHPA, (iv) cidofovir, (v) adefovir, (vi) tenofovir, (vii) stavudine, (viii) HEPT, (ix) TIBO, and (x) AMD3100. Successful drug development, as is certainly true for antiviral drugs and exemplified for the acyclic nucleoside phosphonates cidofovir, adefovir and tenofovir, requires patience and perseverance, and a close continuous and dedicated interaction between Chemistry, Biology/Medicine and Industry.

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Efficiency and selectivity of (E)-5-(2-bromovinyl)-2′-deoxyuridine and some other 5-substituted 2′-deoxypyrimidine nucleosides as anti-herpes agents

Cited by 34 publications

References 18 publications

Susceptibility of bovid herpesvirus 1 to antiviral drugs: in vitro versus in vivo efficacy of (E)-5-(2-Bromovinyl)-2'-deoxyuridine

Susceptibility of bovid herpesvirus 1 to antiviral drugs: in vitro versus in vivo efficacy of (E)-5-(2-Bromovinyl)-2'-deoxyuridine

Effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine on proliferation of human fibroblasts, peripheral blood mononuclear cells, and granulocyte-monocyte progenitor cells in vitro

The discovery of antiviral agents: Ten different compounds, ten different stories

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