Stening G, Gotthammar B, Larsson A, Alenius S, Johansson N G, Oberg B
Antiviral Res. 1981 Nov;1(4):213-23. doi: 10.1016/0166-3542(81)90012-7.
5-(1-Propenyl)-1-beta-D-arabinofuranosyluracil has been synthesized, and this compound and [E]-5-(-propenyl)-2'-deoxyuridine have been tested for inhibition of herpes virus multiplication. Only [E]-5-(1-propenyl)-2'-deoxyuridine was found to be an active inhibitor reducing by 50% the plaque formation of herpes simplex virus type 1 (HSV-1) at about 1 muM. A comparison to the bromovinyl derivatives showed the following order of descending activity; [E]-5-(2-bromovinyl)-2'-deoxyuridine greater than 5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil greater than or equal to [E]-5-(1-propenyl)-2'-deoxyuridine greater than 5-(1-propenyl)-1-beta-arabinofuranosyluracil. HSV-1 mutants lacking thymidine kinase or resistant against acycloguanosine were resistant against [E]-5-(1-propenyl)-2'-deoxyuridine. All compounds seemed to be phosphorylated by HSV-1 thymidine kinase in a cell-free assay. The compounds were phosphorylated to a lower extent by cellular or HSV-2 thymidine kinase, and the HSV-2 strains tested were inhibited by less than 50% at 100 muM in plaque assays. A selective inhibition of HAV-1 DNA synthesis by [E]-5-(1-propenyl)-2'-deoxyuridine was observed in infected cells indicating an effect on viral DNA polymerase. [E]-5-(1-Propenyl)-2'-deoxyuridine had a low cellular toxicity and a therapeutic effect when applied topically to HSV-1-infected guinea pig skin.
5-(1-丙烯基)-1-β-D-阿拉伯呋喃糖基尿嘧啶已被合成，并且对该化合物和[E]-5-(1-丙烯基)-2'-脱氧尿苷进行了抑制疱疹病毒增殖的测试。仅发现[E]-5-(1-丙烯基)-2'-脱氧尿苷是一种活性抑制剂，在约1μM时可使1型单纯疱疹病毒（HSV-1）的噬斑形成减少50%。与溴乙烯基衍生物的比较显示出以下活性递减顺序：[E]-5-(2-溴乙烯基)-2'-脱氧尿苷＞5-(2-溴乙烯基)-1-β-D-阿拉伯呋喃糖基尿嘧啶≥[E]-5-(1-丙烯基)-2'-脱氧尿苷＞5-(1-丙烯基)-1-β-阿拉伯呋喃糖基尿嘧啶。缺乏胸苷激酶或对阿昔洛韦耐药的HSV-1突变体对[E]-5-(1-丙烯基)-2'-脱氧尿苷耐药。在无细胞试验中，所有化合物似乎都被HSV-1胸苷激酶磷酸化。这些化合物被细胞或HSV-2胸苷激酶磷酸化的程度较低，并且在噬斑试验中，所测试的HSV-2毒株在100μM时的抑制率小于50%。在感染细胞中观察到[E]-5-(1-丙烯基)-2'-脱氧尿苷对HSV-1 DNA合成有选择性抑制作用，表明其对病毒DNA聚合酶有影响。[E]-5-(1-丙烯基)-2'-脱氧尿苷局部应用于HSV-1感染的豚鼠皮肤时具有低细胞毒性和治疗作用。
