Antiviral and antimetabolic activities of formycin and its N1-, N2-, 2'-O- and 3'-O-methylated derivatives.

Formycin A, formycin B, and the N₁-, N₂-, 2′-O- and 3′-O-methyl derivatives of formycin A, were all examined for activity against vaccinia, herpes simplex and vesicular stomatitis viruses in primary rabbit kidney cells. The susceptibilities of calf intestinal adenosine deaminase to all the formycin A derivatives, relative to those of some adenosine analogues, were measured in order to take into account the possible effects of intracellular deamination on the antiviral and cytotoxic effects of the formycin derivatives. Formycin B was found to be inactive in all assay systems. Formycin A exhibited significant antiviral activity only against vesicular stomatitis virus, but it also proved relatively toxic to the host cells, appreciably inhibiting cellular DNA and RNA sunthesis as measured by incorporation of labelled thymidine and uridine, respectively. Of the methylated analogues, N₁-methylformycin A (which was highly resistant to enzymatic deamination) and the 2′-O-metyhlderivatives of formycin A were totally inactive in all three viral assay systems. Only N₂-methylformycin exhibited relatively high activity againts vaccinia virus, was not toxic to the cells, and did not affect cellular DNA and RNA synthesis.