Ostrowski Tomasz, Golankiewicz Bozenna, De Clercq Erik, Balzarini Jan
Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul.Noskowskiego 12/14, 61-704 Poznan, Poland.
Bioorg Med Chem. 2005 Mar 15;13(6):2089-96. doi: 10.1016/j.bmc.2005.01.004.
A series of fluorine containing tricyclic analogues of acyclovir (ACV, 1) and ganciclovir (GCV, 2) were synthesized and evaluated for their activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and cytostatic activity against HSV-1 thymidine kinase (TK) gene-transduced human osteosarcoma tumour cells. It was found that fluorine substitution reduced the antiviral activity, but most of the new compounds were pronounced cytostatic agents with potency and selectivity similar to those of parental ACV and GCV. Compounds 12, 13 and 16 seem to be promising as labeled substrates for (19)F NMR studies of the HSV TK-ligand interaction and/or monitoring of their metabolites in cells expressing HSV TK.
合成了一系列阿昔洛韦（ACV，1）和更昔洛韦（GCV，2）的含氟三环类似物，并评估了它们对1型单纯疱疹病毒（HSV-1）和2型单纯疱疹病毒（HSV-2）的活性以及对HSV-1胸苷激酶（TK）基因转导的人骨肉瘤肿瘤细胞的细胞抑制活性。结果发现，氟取代降低了抗病毒活性，但大多数新化合物是明显的细胞抑制剂，其效力和选择性与亲本ACV和GCV相似。化合物12、13和16有望作为用于HSV TK-配体相互作用的（19）F NMR研究和/或监测表达HSV TK的细胞中其代谢物的标记底物。
