2',3'-二脱氧-β-L-5-氟胞苷（β-L-FddC）和2',3'-二脱氧-β-L-胞苷（β-L-ddC）在体外对乙型肝炎病毒和1型人类免疫缺陷病毒的抗病毒活性。
Antiviral activity of 2',3'-dideoxy-beta-L-5-fluorocytidine (beta-L-FddC) and 2',3'-dideoxy-beta-L-cytidine (beta-L-ddC) against hepatitis B virus and human immunodeficiency virus type 1 in vitro.
作者信息
Lin T S, Luo M Z, Liu M C, Pai S B, Dutschman G E, Cheng Y C
机构信息
Department of Pharmacology and the Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06510.
出版信息
Biochem Pharmacol. 1994 Jan 20;47(2):171-4. doi: 10.1016/0006-2952(94)90002-7.
2',3'-Dideoxy-beta-L-5-fluorocytidine (beta-L-FddC) and 2',3'-dideoxy-beta-L-cytidine (beta-L-ddC), two nucleosides with "unnatural L-configuration," have been synthesized and found to have potent antiviral activity against hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1) in vitro with very little toxicity. At 1 microM, both beta-L-ddC and beta-L-FddC inhibited the growth of HBV by more than 90%, while at the same concentration the D-configuration counterparts, 2',3'-dideoxy-beta-D-cytidine (ddC) and 2',3'-dideoxy-beta-D-5-fluorocytidine (beta-D-FddC), did not show antiviral activity against HBV. The order of anti-HIV-1 activity was beta-L-FddC > ddC; beta-D-FddC > beta-L-ddC. The dose-limiting toxicity of ddC is neuropathy which is believed to be caused by the inhibition of the synthesis of mitochondrial DNA. ddC severely inhibited the mitochondrial DNA synthesis of CEM cells yielding an IC50 value of 0.022 microM. Conversely, both beta-L-FddC and beta-L-ddC did not demonstrate any inhibition against mitochondrial DNA synthesis up to 100 microM concentration.
2',3'-二脱氧-β-L-5-氟胞苷（β-L-FddC）和2',3'-二脱氧-β-L-胞苷（β-L-ddC）这两种具有“非天然L构型”的核苷已被合成，并发现它们在体外对乙型肝炎病毒（HBV）和1型人类免疫缺陷病毒（HIV-1）具有强大的抗病毒活性，且毒性极小。在1微摩尔浓度下，β-L-ddC和β-L-FddC均能抑制超过90%的HBV生长，而在相同浓度下，D构型的对应物2',3'-二脱氧-β-D-胞苷（ddC）和2',3'-二脱氧-β-D-5-氟胞苷（β-D-FddC）对HBV没有显示出抗病毒活性。抗HIV-1活性的顺序为β-L-FddC > ddC；β-D-FddC > β-L-ddC。ddC的剂量限制性毒性是神经病变，据信这是由线粒体DNA合成的抑制引起的。ddC严重抑制CEM细胞的线粒体DNA合成，IC50值为0.022微摩尔。相反，在浓度高达100微摩尔时，β-L-FddC和β-L-ddC对线粒体DNA合成均未表现出任何抑制作用。
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