Zagorodniaia S D, Nesterova N V, Golovan' A V, Alekseeva I V, Palchikovs'kaia L I, Baranova G V
Mikrobiol Z. 2011 Nov-Dec;73(6):41-9.
Epstein-Barr virus (EBV) causes several lymphoproliferative diseases, lesions of the central and peripheral nervous systems. Spectrum of etiotropic medicines against EBV is limited. The paper presents the anti-virus research of modified nucleoside with a wide spectrum of action - 6-azacytidine and its derivatives (2'-3'-seco-5-methyl-6-AC, 2',3'-dideoxy-2',3'-didehydro-6-AC and 2'-deoxy-6-AC) on the model of Epstein-Barr virus in Raji lymphoblastoid cells. Parameters of cytotoxicity (CC,) for the investigated substances were determined which amounted to 120 microg/ml, 180 microg/ml, 500 microg/ml, 330 microg/ml, and the effective concentration (ECU)--0.5 microg/ml. 1 microg/ml, 4 microg/ml, 11 microg/ml, in accordance with the sequence of preparations listed above. The results indicate a high antiEBV activity since their selectivity indexes (SI) were 240, 180, 125, 30 that is 1.3-10 times higher than the reference substance acycloguanosine. Apoptosis-stimulating action of 6-azacytidine and its derivatives was revealed. An increase of percentage of apoptotic cells in EBV-infected Raji cells and those treated with investigated substances as compared to uninfected ones was observed after 24 hours. Thus, our results provide new biological properties of the azacytidine substances.
爱泼斯坦-巴尔病毒(EBV)可引发多种淋巴增殖性疾病以及中枢和外周神经系统病变。针对EBV的嗜性药物种类有限。本文介绍了具有广泛作用谱的修饰核苷——6-氮杂胞苷及其衍生物(2'-3'-断键-5-甲基-6-AC、2',3'-二脱氧-2',3'-二脱氢-6-AC和2'-脱氧-6-AC)在拉吉淋巴母细胞样细胞的爱泼斯坦-巴尔病毒模型上的抗病毒研究。测定了所研究物质的细胞毒性参数(CC),分别为120微克/毫升、180微克/毫升、500微克/毫升、330微克/毫升,以及有效浓度(ECU)——0.5微克/毫升、1微克/毫升、4微克/毫升、11微克/毫升,与上述制剂顺序一致。结果表明其具有较高的抗EBV活性,因为它们的选择性指数(SI)分别为240、180、125、30,比参考物质阿昔洛韦高1.3至10倍。揭示了6-氮杂胞苷及其衍生物的促凋亡作用。24小时后观察到,与未感染的细胞相比,EBV感染的拉吉细胞以及用所研究物质处理的细胞中凋亡细胞的百分比增加。因此,我们的结果揭示了氮杂胞苷类物质的新生物学特性。