INVITRO ANTI-HERPESVIRAL ACTIVITY OF 5-ALKYL DERIVATIVES OF 1-BETA-D-ARABINOFURANOSYLURACIL

Several 5-alkyl derivatives of 1-.beta.-D-arabinofuranosyluracil (araU) were tested for anti-herpesviral activity and inhibitory action on cell growth in human embryonic lung fibroblasts. 1-.beta.-D-Arabinofuranosylcytosine, 9-.beta.-D-arabinofuranosyladenine [araA] and 5-iododeoxyuridine (IUdR) were included as reference materials. Among the 5-alkyl derivatives of araU, arabinosylthymine [araT] was the most active, followed by 5-ethyl and 5-propyl-araU. 5-Ethyl-araU was as active as IUdR and more active than araA against herpes simplex virus (HSV) type 1 and did not inhibit cell growth at a concentration as high as 1000 .mu.g/ml. 5-Butyl- and 5-methoxymethyl-araU and araU exhibited relatively low activity. The araU derivatives tested were as active against HSV WT-34, an isolate from a patient with keratitis, as against HSV type 1. Against an IUdR-resistant isolate, HSV WT-20, araT was less inhibitory than IUdR. DNA synthesis in HSV type 1-infected cells was markedly inhibited by araT, IUdR, and 5-ethyl-araU whereas cellular DNA synthesis in uninfected cells was significantly inhibited by IUdR but not by araT or 5-ethyl-araU.