Antiviral activities of 2'-deoxyribofuranosyl and arabinofuranosyl analogs of sangivamycin against retro- and DNA viruses.
Eight sugar-modified pyrrolopyrimidine nucleoside analogs related to the antibiotic sangivamycin were evaluated in cell culture against herpes simplex types 1 (HSV-1) and 2 (HSV-2), cytomegalovirus (CMV), adenovirus, and visna virus. Five of the compounds were highly active against most of the viruses with 50% inhibition (ED50) values of 1-10 microM. The selectivity of the agents was low, with inhibition of uninfected cell proliferation occurring within 5-fold that of the virus ED50 for most of the viruses. The compounds did not possess RNA virus-inhibitory activity when evaluated against certain myxo-, paramyxo-, picorna-, reo-, rhabdo-, and togaviruses. Two of the nucleosides were tested further in a cell line persistently infected with Friend leukemia virus where they were inhibitory to both virus yield and cell proliferation at 4-5 microM. Several of the sangivamycin analogs were tested in animal models using a twice-a-day treatment regimen. They proved to be inactive against HSV-1, murine CMV and/or Friend leukemia virus infections in mice.
Smee
D F
DF
Nucleic Acid Research Institute, Costa Mesa, California 92626.
McKernan
P A
PA
Alaghamandan
H A
HA
Frank
K B
KB
Ramasamy
K
K
Revankar
G R
GR
Robins
R K
RK
D000256:Adenoviridae / Q000187:drug effects; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000188:drug therapy; D004267:DNA Viruses / Q000187:drug effects*; D005622:Friend murine leukemia virus / Q000187:drug effects; D006561:Herpes Simplex / Q000188:drug therapy; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D011741:Pyrimidine Nucleosides / Q000494:pharmacology / Q000627:therapeutic use; D012190:Retroviridae / Q000187:drug effects*; D018139:Simplexvirus / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014790:Visna-maedi virus / Q000187:drug effects
D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides; C005699:sangivamycin