DEGLYCOSYLATION OF ANTIHERPESVIRAL 5-SUBSTITUTED ARABINOSYLURACIL DERIVATIVES BY RAT-LIVER EXTRACT AND ENTEROBACTERIA CELLS

A number of antiherpesviral 5-substituted derivatives of 1-beta-D-arab inofuranosyluracil (araU) were significantly resistant to phosphorolys is by rat liver extract (S-9), but were gradually deglycosylated in a 2% enterobacteria cell suspension. The relative order of the resistanc e conferred by the different C-5 substituents was: 5-propynyl > 5-(E)- 2-bromovinyl > 5-(E)-2-chlorovinyl > 5-methyl > 5-iodo. The 2'-fluoro derivatives of araU were completely resistant to phosphorolysis by bot h liver extract and enterobacteria, whereas the corresponding ribofura nosyl and 2'-deoxyribofuranosyl nucleosides were easily phosphorolysed by S-9, and were immediately cleaved in a 1% enterobacteria cell susp ension. These findings suggest that antiherpesviral 5-substituted araU analogues can be relatively stable in vivo, when injected intravenous ly, and that degradation of 1-beta-D-arabinofuranosyl-5-(E-2-bromoviny l)uracil (sorivudine) following oral administration is due primarily t o the action of enterobacteria.