In vitro antiherpesviral activity of 5-alkyl derivatives of 1-beta-D-arabinofuranosyluracil.
Several 5-alkyl derivatives of 1-beta-d-arabinofuranosyluracil (araU) were tested for antiherpesviral activity and inhibitory action on cell growth in human embryonic lung fibroblasts. 1-beta-d-Arabinofuranosylcytosine, 9-beta-d-arabinofuranosyladenine, and 5-iododeoxyuridine (IUdR) were included as reference materials. Among the 5-alkyl derivatives of araU, arabinosylthymine was the most active, followed by 5-ethyl- and 5-propyl-araU. 5-Ethyl-araU was as active as IUdR and more active than 9-beta-d-arabinofuranosyladenine against herpes simplex virus (HSV) type 1 and did not inhibit cell growth at a concentration as high as 1,000 mug/ml. 5-Butyl- and 5-methoxymethyl-araU, as well as 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, arabinosylthymine was less inhibitory than IUdR. Deoxyribonucleic acid synthesis in HSV type 1-infected cells was markedly inhibited by arabinosylthymine, IUdR, and 5-ethyl-araU, whereas cellular deoxyribonucleic acid synthesis in uninfected cells was significantly inhibited by IUdR but not by arabinosylthymine or 5-ethyl-araU.
D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D006561:Herpes Simplex / Q000188:drug therapy*; D013936:Thymidine / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives*
D001086:Arabinofuranosyluracil; D004247:DNA; D013936:Thymidine; D014529:Uridine