[(E)-5-(2-bromovinyl)-2'-desoxyuridine--a new nucleoside analog with selective inhibitory action against herpesviruses. Studies in cell culture and animal experiments].
(E)-5-(2-Bromovinyl)-2'-deoxyuridine (1; BrVUdR) inhibits the replication of herpes simplex virus type 1 (HSV-1) and of varicella-zoster virus (VZV) in vitro at concentrations of 0.01 to 0.23 mumol/l, whereas herpes simplex virus type 2 (HSV-2) is influenced only at 5.5 to 27 mumol/l. In comparison to some classical and newly developed antiherpetics, i. e. 5-iodo-2'-desoxyuridine (2; idoxuridine, IDU), 9-beta-D-arabinofuranosyladenine (4; vidarabine Ara-A), 9-(2-hydroxyethoxymethyl) guanine (5; acyclovir, ACV) and 2'-fluoro-5-iodo-1-beta-D-aracytosine (6;FIAC) the following order of decreasing activity was found:1 greater than 6 greater than 5 greater than 2 greater than 4 (against HSV-1) and 6 greater than 2 greater than 5 greater than 1 greater than 4 (against HSV-2). The high selectivity of the antiviral effect of BrVUdR towards HSV-1 and TZV is based on the fact, that proliferation of different mammalian cell lines is inhibited by 50% only at concentrations as high as 90 to 170 mumol/l, resulting in a therapeutical index of 1000 to 10,000. Successful treatment of an HSV-1 encephalitis in mice as well as an HSV-1 keratitis of rabbits confirmed the efficiency of 1 in experimental animal infections. No toxic side effects in both local and systemic applications were observed. Promising data from cell culture and animal experiments recommend 1 as a potential candidate for the local and systemic treatment of HSV-1 and VZV infections in man.
Reefschläger
J
J
Abteilung Molekulare Virologie und Chemotherapie, Bereiches Medizin (Charité) der Humboldt-Universität zu Berlin.
Wutzler
P
P
Thiel
K D
KD
Töpke
H
H
Bärwolff
D
D
Langen
P
P
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D004660:Encephalitis / Q000188:drug therapy; D006564:Herpesviridae / Q000187:drug effects*; D006566:Herpesviridae Infections / Q000188:drug therapy; D006801:Humans; D007634:Keratitis / Q000188:drug therapy; D018139:Simplexvirus / Q000187:drug effects
D000998:Antiviral Agents; C020235:brivudine; D001973:Bromodeoxyuridine
(E)-5-(2-Bromvinyl)-2'-desoxyuridin--ein neues Nucleosidanalogon mit selektiver Hemmwirkung gegenüber Herpesviren. Untersuchungen in der Zellkultur und im Tierexperiment.