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Antimicrob Agents Chemother. 1977 February; 11(2): 191-197
Copyright © 1977 American Society for Microbiology. All Rights Reserved.

Antiviral Activities of Acyl Derivatives of 2,2'-Anhydro-1-ß-D-Arabinofuranosylcytosine and 1-ß-D-Arabinofuranosylcytosine in Cell Culture¹

^* Shionogi Research Laboratory, Shionogi & Co., Ltd., Fukushima-ku, Osaka, 553 Japan
Institute of Molecular Biology, Syntex Research, Palo Alto, California 94304

ABSTRACT

Antiviral activities of acyl derivatives (3'-O-octanoyl and 3'-O-decanoyl) of 2,2'-anhydro-1-ß-D-arabinofuranosylcytosine (cyclo-C) and 1-ß-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-ß-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.

¹ Contribution no. 129 from the Institute of Molecular Biology, Syntex Research, Palo Alto, CA 94304.