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

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 an...

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Veröffentlicht in:FEBS letters 1995-10, Vol.373 (1), p.41-44
Hauptverfasser: Balzarini, J., Andrei, G., Kumar, R., Knaus, E.E., Wiebe, L.I., De Clercq, E.
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container_end_page 44
container_issue 1
container_start_page 41
container_title FEBS letters
container_volume 373
creator Balzarini, J.
Andrei, G.
Kumar, R.
Knaus, E.E.
Wiebe, L.I.
De Clercq, E.
description 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.
doi_str_mv 10.1016/0014-5793(95)00994-K
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source MEDLINE; Elsevier ScienceDirect Journals Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Animals
Antineoplastic Agents - pharmacology
Antiviral Agents - pharmacology
Azides - pharmacology
Azidovinyldeoxyuridine
Cell Division - drug effects
Deoxyuridine - analogs & derivatives
Deoxyuridine - pharmacology
Gene therapy
Herpes simplex virus
Herpesvirus 3, Human - drug effects
Herpesvirus 3, Human - physiology
Mammary Neoplasms, Experimental
Mice
Mice, Inbred C3H
Molecular Structure
Recombinant Proteins - biosynthesis
Simplexvirus - drug effects
Simplexvirus - genetics
Simplexvirus - physiology
Structure-Activity Relationship
Thymidine kinase
Thymidine Kinase - biosynthesis
Thymidylate synthase
Transfection
Tumor Cells, Cultured
varicella-zoster virus
Virus Replication - drug effects
title 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
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