Immunomodulatory and antiviral activities of 2',3'-dideoxy-beta-L-cytidine and 2',3'-dideoxy-beta-L-5-fluorocytidine.
Two dideoxynucleosides, 2',3'-dideoxy-beta-L-cytidine and 2',3'-dideoxy-beta-L-5-flurocytidine, containing unnatural L-configuration in their sugar moieties, were synthesized and assayed for antiviral activities. Both compounds were shown to possess potent anti-human immunodeficiency virus type 1 and antihepatitis B virus activities, while demonstrating no anti-herpes simplex viruses 1 and 2 activity. These two compounds exhibited in vitro cellular toxicities for several leukocytic cell lines and were shown to inhibit phytohemagglutinin-stimulated human peripheral blood mononuclear leukocyte proliferations. At inhibitory concentrations, both compounds caused accumulations of cells in the S phase. While demonstrating no obvious morphological toxicity in vivo in mice at concentrations of 75 and 150 mg/kg, 2',3'-dideoxy-beta-L-5-fluorocytidine- treated animals were shown to have considerable increases in CD4/CD8 double positive T lymphocyte population in their blood circulation.
Gagnon
L
L
Virol./Immunol. Dept., BioChem Therapeutic Inc., Québec, Canada.
Nordstrom
P A
PA
Duchaine
J
J
Jutras
D
D
Hamel
M
M
Barbeau
D
D
Hooker
E
E
Ashman
C
C
Cammack
N
N
Tse
A
A
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002522:Chlorocebus aethiops; D006678:HIV / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D018139:Simplexvirus / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; C085719:2',3'-dideoxy-beta-5-fluorocytidine; D016047:Zalcitabine