β-2',3'-二脱氧胞苷类似物的纯核苷对映体在体外是乙型肝炎病毒的选择性抑制剂。
Pure nucleoside enantiomers of beta-2',3'-dideoxycytidine analogs are selective inhibitors of hepatitis B virus in vitro.
作者信息
Schinazi R F, Gosselin G, Faraj A, Korba B E, Liotta D C, Chu C K, Mathé C, Imbach J L, Sommadossi J P
机构信息
Georgia VA Research Center for AIDS and HIV Infections, Veterans Affairs Medical Center, Decatur 30033.
出版信息
Antimicrob Agents Chemother. 1994 Sep;38(9):2172-4. doi: 10.1128/AAC.38.9.2172.
Abstract
(-)-beta-L-2',3'-Dideoxycytidine (beta-L-DDC), (+)-beta-D-2',3'-dideoxycytidine (beta-D-DDC), (-)-beta-L-2',3'-dideoxy-5-fluorocytidine (beta-L-FDDC), (-)-beta-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine (beta-L-FTC), and (+)-beta-D-1,3-dioxolane-5-fluorocytidine (beta-D-FDOC) were evaluated for their anti-hepatitis B virus (anti-HBV) activities in HBV-transfected human liver cells (2.2.15). The order of decreasing potency for the compounds at the 90% effect level was beta-D-FDOC > beta-L-FTC > beta-L-FDDC approximately beta-L-DDC >> beta-D-DDC. Inhibition of HBV in transfected liver cells by the cytosine nucleosides was selective. The beta-L-nucleoside-5'-triphosphates were consistently more potent inhibitors of woodchuck hepatitis virus DNA polymerase than the corresponding natural beta-D-enantiomers.
摘要
对（-）-β-L-2'，3'-二脱氧胞苷（β-L-DDC）、（+）-β-D-2'，3'-二脱氧胞苷（β-D-DDC）、（-）-β-L-2'，3'-二脱氧-5-氟胞苷（β-L-FDDC）、（-）-β-L-2'，3'-二脱氧-5-氟-3'-硫代胞苷（β-L-FTC）和（+）-β-D-1，3-二氧戊环-5-氟胞苷（β-D-FDOC）在乙肝病毒（HBV）转染的人肝细胞（2.2.15）中进行了抗乙肝病毒（抗HBV）活性评估。在90%效应水平下，这些化合物效力递减顺序为β-D-FDOC＞β-L-FTC＞β-L-FDDC≈β-L-DDC＞＞β-D-DDC。胞嘧啶核苷对转染肝细胞中HBV的抑制具有选择性。β-L-核苷-5'-三磷酸作为土拨鼠肝炎病毒DNA聚合酶抑制剂始终比相应的天然β-D-对映体更有效。
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1
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J Med Chem. 1993 Mar 5;36(5):519-28. doi: 10.1021/jm00057a001.
2
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Biochem Pharmacol. 1993 Apr 6;45(7):1540-3. doi: 10.1016/0006-2952(93)90058-5.
3
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4
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Hosp Pract (Off Ed). 1994 Feb 15;29(2):117-20, 123-6, 129-32. doi: 10.1080/21548331.1994.11442979.
5
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6
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7
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