Inhibition of replication of hepatitis B virus by cytallene in vitro.
Inhibition of replication of hepatitis B virus by cytallene in vitro.
复制标题
胞二烯在体外抑制乙型肝炎病毒的复制。
DOI：
10.1128/aac.41.8.1755
复制
发表时间：
1997
影响因子：
4.9
通讯作者：
Cheng,YC
中科院分区：
文献类型：
--
作者：
Zhu,YL;Pai,SB;Liu,SH;Grove,KL;Jones,BC;Simons,C;Zemlicka,J;Cheng,YC
无环胞嘧啶核苷类似物环tallene[1-（4'-羟基-1',2'-丁二烯基）胞嘧啶]具有(+)-和(-)-对映体，在2.2.15个细胞中对其抗乙型肝炎病毒（HBV）活性进行了评估，发现对HBV DNA合成具有有效活性。R-(-)-对映体是胞烯对映体中活性更高的，对HBV合成的抑制浓度（HBIC50）为0.08微米，达到50%。其抗病毒活性可被脱氧胞苷（dC）逆转，而胞苷的抗病毒活性较低。从培养基中去除R-(-)-对映体后，HBV DNA的合成可以重新启动，这表明抗病毒作用是可逆的。R-(-)-对映体也被发现比S-(+)-对映体更有细胞毒性。不同细胞系的细胞毒性程度不同，大于10微米时细胞生长抑制率为50%。R-(-)-对映体在浓度为HBIC50的10倍或以上时对HBV RNA合成和线粒体DNA合成无影响。这两个对映体不能被dC脱氨酶脱氨，它们可以被胞质dC激酶磷酸化。环丙烯的R-(-)-对映体是第一个对HBV具有强抑制活性的无环胞嘧啶类似物，类似于其他L-(-)- ddc类似物。
The acyclic cytosine nucleoside analog cytallene [1-(4'-hydroxy-1',2'-butadienyl)cytosine], which has both (+)- and (-)-enantiomers, was evaluated for its anti-hepatitis B virus (HBV) activity in 2.2.15 cells and was found to have potent activity against HBV DNA synthesis. The R-(-)-enantiomer was found to be the more active of the cytallene enantiomers, with a 50% inhibition concentration against HBV synthesis (HBIC50) of 0.08 microM. Its antiviral activity could be reversed by deoxycytidine (dC) and less efficiently by cytidine. Upon removal of the R-(-)-enantiomer from culture medium, the synthesis of HBV DNA could reinitiate, which suggested that the antiviral action is reversible. The R-(-)-enantiomer was also found to be more cytotoxic than the S-(+)-enantiomer. The degree of cytotoxicity varied among the cell lines, with a 50% inhibition of cell growth at greater than 10 microM. The R-(-)-enantiomer had no effect on HBV RNA synthesis and mitochondrial DNA synthesis at a concentration of 10 times or more than the HBIC50. The two enantiomers cannot be deaminated by dC deaminase, and they can be phosphorylated by cytoplasmic dC kinase. The R-(-)-enantiomer of cytallene is the first acyclic cytosine analog with potent inhibitory activity against HBV similar to those of other L-(-)-ddC analogs.