The cytostatic activity of 5-(1-azidovinyl)-2′-deoxyuridine (AzVDU) against herpes simplex virus thymidine kinase gene-transfected FM3A cells is due to inhibition of thymidylate synthase and enhanced by UV light ( λ = 254 nm) exposure

Abstract

5-(1-Azidovinyl)-2′-deoxyuridine (AzVDU) and a series of 5-[1-azido-2-halogenoethyl]-derivatives of β- d-arabinofuranosyluracil (AU) proved markedly inhibitory to the replication of herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV), but not thymidine kinase (TK)-deficient HSV-1 and VZV strains. None of the compounds were cytostatic. However, AzVDU, but not the 5-[1-azido-2-halogenoethyl]-AU derivatives became highly cytostatic against HSV-1 and HSV-2 TK genetransfected FM3A tumor cells. The molecular target for the cytostatic effect of AzVDU proved to be thymidylate synthase. Short exposure of AzVDU-treated FM3A TK −/HSV-1 TK + cells to irradiation at λ = 254 nm enhanced the cytostatic activity of AzVDU by 5-fold.