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

FEBS Letters

Andrei, G.²  Balzarini, J.²  Knaus, E.E.¹  Kumar, R.¹  Wiebe, L.I.¹  De Clercq, E.² 

[1] Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8, Canada;Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

关键词: Azidovinyldeoxyuridine;    Herpes simplex virus;    Thymidine kinase;    Gene therapy;    Thymidylate synthase;   

DOI  :  10.1016/0014-5793(95)00994-K

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown