Cerný J, Votruba I, Vonka V, Rosenberg I, Otmar M, Holý A
Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague.
Antiviral Res. 1990 May;13(5):253-64. doi: 10.1016/0166-3542(90)90070-n.
Diphosphates of N-(S)-(3-hydroxy-2-phosphonylmethoxypropyl) and N-(2-phosphonylmethoxyethyl) derivatives of purine and pyrimidine heterocyclic bases inhibit HSV-1 encoded ribonucleotide reductase. Of the compounds studied, the most efficient inhibitors of CDP reduction (at 5.1 mumols.l-1) by the HSV-1-encoded enzyme are HPMPApp (IC50 = 0.9 mumols.l-1) and PMEApp (IC50 = 8 mumol.l-1). PMEApp does not inhibit the enzyme isolated from the mutant HSV-1 KOS strain PMEAr which is resistant to PMEA at a concentration of 100 micrograms/ml. The enzyme isolated from the PMEA-resistant virus strain is also insensitive to inhibitory effects of hydroxyurea and HPMPApp. Thus, the inhibitory potency of HPMPApp and PMEApp toward HSV-1 encoded ribonucleotide reductase might be connected with the anti-HSV activity of HPMPA and PMEA.
嘌呤和嘧啶杂环碱的N-(S)-(3-羟基-2-膦酰甲氧基丙基)和N-(2-膦酰甲氧基乙基)衍生物的二磷酸盐可抑制单纯疱疹病毒1型（HSV-1）编码的核糖核苷酸还原酶。在所研究的化合物中，HSV-1编码的酶对CDP还原（浓度为5.1 μmol·L⁻¹时）最有效的抑制剂是HPMPApp（IC50 = 0.9 μmol·L⁻¹）和PMEApp（IC50 = 8 μmol·L⁻¹）。PMEApp不抑制从突变的HSV-1 KOS菌株PMEAr中分离出的酶，该菌株对浓度为100 μg/ml的PMEA具有抗性。从对PMEA耐药的病毒菌株中分离出的酶对羟基脲和HPMPApp的抑制作用也不敏感。因此，HPMPApp和PMEApp对HSV-1编码的核糖核苷酸还原酶的抑制效力可能与HPMPA和PMEA的抗HSV活性有关。
