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 (lambda = 254 nm) exposure.
5-(1-Azidovinyl)-2'-deoxyuridine (AzVDU) and a series of 5-[1-azido-2-halogenoethyl]-derivatives of beta-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 gene-transfected 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 lambda = 254 nm enhanced the cytostatic activity of AzVDU by 5-fold.
Balzarini
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Andrei
G
G
Kumar
R
R
Knaus
E E
EE
Wiebe
L I
LI
De Clercq
E
E
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001386:Azides / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014645:Herpesvirus 3, Human / Q000187:drug effects / Q000502:physiology; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008809:Mice, Inbred C3H; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000096:biosynthesis; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D013329:Structure-Activity Relationship; D013937:Thymidine Kinase / Q000096:biosynthesis*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
C096215:5-(1-azidovinyl)-2'-deoxyuridine; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001386:Azides; D011994:Recombinant Proteins; D013937:Thymidine Kinase; D003857:Deoxyuridine