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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
Author(s) -
Balzarini J.,
Andrei G.,
Kumar R.,
Knaus E.E.,
Wiebe L.I.,
De Clercq E.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00994-k
Subject(s) - thymidylate synthase , thymidine kinase , herpes simplex virus , deoxyuridine , transfection , thymidine , microbiology and biotechnology , biology , virus , thymidine phosphorylase , vero cell , virology , chemistry , enzyme , biochemistry , gene , in vitro , dna , fluorouracil , cancer , genetics
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.