Meerbach A, Holý A, Wutzler P, De Clercq E, Neyts J
Institute for Antiviral Chemotherapy, Friedrich-Schiller-University Jena, Erfurt, Germany.
Antivir Chem Chemother. 1998 May;9(3):275-82. doi: 10.1177/095632029800900309.
The anti-Epstein-Barr virus (EBV) activity of different classes of compounds was assessed by means of an EBV DNA hybridization assay using a digoxigenin-labelled probe specific for the BamHI W fragment of the EBV genome, as well as by measuring viral capsid antigen (VCA) expression after a 7 day incubation period of P3HR-1 producer cells with the test substances. Acyclovir, ganciclovir, cidofovir and zidovudine were included as reference compounds. Several compounds proved to be potent and selective inhibitors of EBV DNA synthesis and VCA expression. Of the new compounds that were evaluated for their anti-EBV activity, the highest efficacy (lowest EC50) and highest selectivity index (SI) were shown by the purine nucleoside analogue 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (S2242) (EC50 0.6 ng/ml; SI 600), the acyclic nucleoside phosphonate analogues 9-(2-phosphono -methoxyethyl)-6-dimethylaminopurine (EC50 1.1 micrograms/ml; SI 91), 9-(2-phosphonomethoxyethyl)-2- amino-6-benzhydrylaminopurine (EC50 1.3 micrograms/ml; SI 29), 7-(2-phosphonomethoxyethyl)-6-dimethyl-aminopurine (EC50 0.8 microgram/ml; SI 56), 9-(R)-(2-phosphonomethoxypropyl)-6-(2-dimethylaminoethyl)-aminopur ine (EC50 0.5 microgram/ml; SI 42), the 2',3'-dideoxythymidine derivative 3'-oximino-2',3'-dideoxythymidine (EC50 1.5 micrograms/ml; SI 65), and 1-(2,3- dideoxy-3-N-hydroxyamino-beta-D-threo-pentafuranyl)pentafuranos yl)thymine (EC50 4.1 micrograms/ml; SI > 24).
通过使用针对EBV基因组BamHI W片段的地高辛配基标记探针的EBV DNA杂交试验，以及通过在P3HR - 1产生细胞与测试物质孵育7天后测量病毒衣壳抗原（VCA）表达，评估了不同类化合物的抗爱泼斯坦 - 巴尔病毒（EBV）活性。阿昔洛韦、更昔洛韦、西多福韦和齐多夫定作为参考化合物。几种化合物被证明是EBV DNA合成和VCA表达的有效且选择性抑制剂。在评估其抗EBV活性的新化合物中，嘌呤核苷类似物2 - 氨基 - 7 - [(1,3 - 二羟基 - 2 - 丙氧基)甲基]嘌呤（S2242）（EC50 0.6 ng/ml；SI 600）、无环核苷膦酸酯类似物9 - (2 - 膦酰基 - 甲氧基乙基)-6 - 二甲基氨基嘌呤（EC50 1.1微克/ml；SI 91）、9 - (2 - 膦酰基甲氧基乙基)-2 - 氨基 - 6 - 二苯甲基氨基嘌呤（EC50 1.3微克/ml；SI 29）、7 - (2 - 膦酰基甲氧基乙基)-6 - 二甲基 - 氨基嘌呤（EC50 0.8微克/ml；SI 56）、9 - (R)-(2 - 膦酰基甲氧基丙基)-6 - (2 - 二甲基氨基乙基)-氨基嘌呤（EC50 0.5微克/ml；SI 42）、2',3'-二脱氧胸苷衍生物3'-氧代亚氨基 - 2',3'-二脱氧胸苷（EC50 1.5微克/ml；SI 65）和1 - (2,3 - 二脱氧 - 3 - N - 羟基氨基 - β - D - 苏 - 戊呋喃糖基)戊呋喃糖基)胸腺嘧啶（EC50 4.1微克/ml；SI>24）显示出最高的效力（最低的EC50）和最高的选择性指数（SI）。
