title: Antiviral activities of acyl derivatives of 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine and 1-beta-D-arabinofuranosylcytosine in cell culture.
abstract: Antiviral activities of acyl derivatives (3'-O-octanoyl and 3'-O-decanoyl) of 2,2'-anhydro-1-beta-d-arabinofuranosylcytosine (cyclo-C) and 1-beta-d-arabinofuranosylcytosine (Ara-C) were compared with other antiviral nucleosides, and some biological characteristics of the antiviral activity were investigated. Among those synthesized acyl derivatives, 3'-O-decanoyl ara-C was the most active against deoxyribonucleic acid viruses, with an activity comparable to that of Ara-C. Acyl derivatives of cyclo-C were somewhat less active than their Ara-C counterparts. In the value of therapeutic index, 1-beta-d-arabinofuranosyladenine was superior to the others, followed by 5-iodo-2'-deoxyuridine. In comparing the sensitivity of two serotypes of herpes simplex virus it was found that Ara-C and its ester, as well as its cyclo-C counterpart, were more active against the type 2 than the type 1 strain. The activity of 3'-O-decanoyl Ara-C, like that of its parent, was diminished by treatment with cytidine deaminase from mouse kidney, but 3'-O-decanoyl cyclo-C was resistant to this treatment. In comparative studies of 3'- and 5'-O-acyl Ara-C's, antivaccinia virus activity of 3'-O-palmitoyl Ara-C was significantly superior to its 5'-counterpart. The inhibitory activity of 5'-O-decanoyl Ara-C was markedly reduced by the presence of a threefold molar excess of eserine sulfate, a choline esterase inhibitor, whereas the 3'-acyl Ara-C was not affected by the inhibitor in any combination. This result indicates that enzymatic hydrolysis of the 3'-ester to Ara-C, which is inhibited by eserine sulfate, did not occur in this cell culture.
mesh_terms: D000215:Acylation; D003504:Ancitabine / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D002478:Cells, Cultured; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003864:Depression, Chemical; D004352:Drug Resistance, Microbial; D000882:Haplorhini; D006801:Humans; D010830:Physostigmine / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship; D014780:Viruses / Q000254:growth & development
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D003561:Cytarabine; D010830:Physostigmine; D003504:Ancitabine