ANTIHERPESVIRAL AND ANTI-CELLULAR EFFECTS OF 1-BETA-D-ARABINOFURANOSYL-E-5-(2-HALOGENOVINYL) URACILS

1-.beta.-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-ara-U) and 1-.beta.-D-arabinofuranosyl-E-5-(2-chlorovinyl)uracil (CV-ara-U) were tested for their antiherpesviral activity by a virus rating method, a plaque reduction method and a virus yield reduction method, using human embryonic lung fibroblast (HEL-F) cells. At a concentration as low as 0.1 .mu.g/ml, both drugs exerted a marked inhibitory effect on the development of the cytopathogenic effect induced by herpes simplex virus type 1 (HSV-1) infection and on the multiplication and plaque formation of HSV-1. Neither BV-ara-U nor CV-ara-U was significantly active against HSV type 2 (HSV-2). They scarcely inhibited growth of HEL-F cells, mouse L and murine leukemia cells. Compared with 1-.beta.-D-arabinofuranosylthymine and 5-iodo-deoxyuridine, BV-ara-U and CV-ara-U were > 10 times as active against HSV-1 and much less active against HSV-2. BV-ara-U was as active as E-5-(2-bromovinyl)-2''-deoxyuridine against HSV-1 and less inhibitory to growth of HEL-F cells. Cellular DNA synthesis was not significantly influenced by the new derivatives of arabinosyluracil, even at a concentration as high as 300 .mu.g/ml. The derivatives showed extremely marked inhibition of DNA synthesis in HSV-1-infected cells, whereas their inhibitory effect on DNA synthesis in HSV-2-infected cells was much lower than that in HSV-1-infected cells. BV-ara-U and CV-ara-U are evidently selectively inhibitory to HSV-1 multiplication.