2,2'-Anhydro-1-(3'-O-acetyl-beta-D-arabinofuranosyl)-5-iodocytosine (anhydro-araIC 3'-acetate), previously synthesized and isolated as a crude product by Moffatt and his coworkers, was purified and characterized. The availability of pure
anhydro-araIC 3'-acetate made possible a comparative study of the
antineoplastic,
antiviral and biochemical potencies of
anhydro-araIC 3'-acetate with the structurally related agents 2,2'-anhydro-1-(3'-O-acetyl-beta-D-arabinofuranosyl)cytosine (anhydro-araC 3'-acetate) and 2,2'-anhydro-1-(beta-D-arabinofuranosyl)-5-iodocytosine (anhydro-araIC). The presence of the 5-iodo substituent and/or the 3'-O-acetyl group on 2,2'-anhydro1-(beta-D-arabinofuranosyl)cytosine (anhydro-araC) did not alter the capacity of these agents to exert cytotoxic and
antineoplastic activity against L1210, P388, L5178Y and human
leukemia cells and against human colon and rectal
carcinomas, as well as
antiviral activity against herpes simplex virus Type 1. All of the compounds caused inhibition of [3H]
thymidine incorporation into the
DNA of L1210 cells in culture, with
anhydro-araIC 3'-acetate being significantly less inhibitory than the other derivatives. Little or no interference with
RNA and
protein synthesis was produced by these
pyrimidine nucleosides. Both
anhydro-araIC 3'-acetate and anhydro-araIC were potent inhibitors of the activity of
DNA polymerase alpha from the
L1210 leukemia at the
nucleoside level, while anhydro-araC 3'-acetate and anhydroaraC were non-inhibitory; none of the agents caused inactivation of
DNA polymerase beta. The findings suggest that the
antineoplastic and
antiviral activities of the 2,2'-anhydro-arabinosylcytosine
nucleosides may be the result of biochemical actions different from those of araC.