Antiviral, antimetabolic, and cytotoxic activities of 5-substituted 2'-deoxycytidines.

Various 5-substituted 29-deoxycytidines, including 5-bromo-dCyd, 5-iodo-dCyd, 5-nitro-dCyd, 5-ethynyl-dCyd, 5-propyl-dCyd, (E)-5-(2-bromovinyl)-dCyd, and (E)-5-(2-iodovinyl)-dCyd, were evaluated for their antiviral and antimetabolic properties in primary rabbit kidney (PRK) cell cultures and for their inhibitory effects on murine L1210 cell proliferation. All dCyd analogues proved to be selective inhibitors of herpes simplex virus (HSV) replication: 5-bromo-dCyd, 5-iodo-dCyd, 5-nitro-dCyd, and 5-ethynyl-dCyd were more selective in their anti-HSV activity than were the corresponding 5-substituted 29-deoxyuridines, whereas 5-propyl-dCyd, (E)-5-(2-bromovinyl)-dCyd, and (E)-5-(2-iodovinyl)-dCyd were as selective as their dUrd counterparts. The dCyd analogues were also less cytotoxic (for both PRK and L1210 cells), as could be monitored by inhibition of either cell proliferation or host-cell DNA synthesis (incorporation of radiolabeled precursors). Of all 5-substituted 29-deoxycytidines tested, the (E)-5-(2-halogenovinyl) derivatives emerged as the most potent and most selective inhibitors of HSV (Type 1) replication.