Antiviral effect of antileukemic drugs N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC) and 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine (cyclo-C) against human cytomegalovirus.
The antiviral activities of antileukemic drugs 1-beta-D-arabinofuranosylcytosine (Cytarabine; Ara-C), 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine (Ancitabine; Cyclo-C), and N4-behenoyl-1-beta-D-arabinofuranosylcytosine (Enocitabine; BH-AC) were evaluated in vitro against human cytomegalovirus (HCMV) in comparison with those of five other antiviral drugs. Both Ara-C and Cyclo-C showed the strongest inhibitory effect to HCMV. BH-AC inhibited the replication of HCMV and depicted almost as the same dose-response curve as Ganciclovir (DHPG). In the presence of Ara-C, Cyclo-C, or BH-AC, triphosphate forms of the nucleoside analogs were detected in the HCMV-infected cells, and synthesis of HCMV DNA was strongly suppressed. Thus, Ara-C, Cyclo-C, and BH-AC were not only antileukemic, but also antiviral in vitro. However, Ara-C and Cyclo-C may not be suitable as anti-HCMV agents, because they are cytotoxic or excreted rapidly in the urine in vivo [Van Voris, 1984; Hirayama et al., 1974]. Because of lower toxicity and longer retention in vivo, BH-AC may be expected as an anti-HCMV agent in patients with leukemia, in addition to serving as an antileukemic drug.
Nakamura
K
K
Department of Microbiology, Miyazaki Medical College, Japan.
Eizuru
Y
Y
Kumura
K
K
Minamishima
Y
Y
D003504:Ancitabine / Q000378:metabolism / Q000494:pharmacology*; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000032:analysis; D005347:Fibroblasts; D006801:Humans; D009711:Nucleotides / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D009711:Nucleotides; D003561:Cytarabine; C015019:enocitabine; D003504:Ancitabine