新型2,6-二氨基嘌呤类似物β-LPA对乙型肝炎病毒体外复制的抑制作用

Inhibition of the replication of hepatitis B virus in vitro by a novel 2,6-diaminopurine analog, beta-LPA.

作者信息

He Xing-Xing, Chen Ting, Lin Ju-Sheng, Chang Ying, Ye Bai-Xin

机构信息

Institute of Liver Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Biochem Biophys Res Commun. 2008 May 2;369(2):513-8. doi: 10.1016/j.bbrc.2008.02.039. Epub 2008 Feb 20.

DOI:10.1016/j.bbrc.2008.02.039

PMID:18284916

Abstract

Antiviral therapy of chronic hepatitis B remains a major clinical problem worldwide. Like lamivudine, nucleoside analogs have become the focus of investigation of anti-hepatitis B virus (anti-HBV) drugs. Here, beta-LPA is a novel 2,6-diaminopurine analog found to possess potent anti-HBV activity. In HepG2.2.15 cell line, beta-LPA had a 50% effective concentration (EC(50)) of 0.01 microM against HBV, as determined by analysis of secreted and intracellular episomal HBV DNA. Levels of HBV surface antigen (HBsAg) and e antigen (HBeAg) in drug-treated cultures revealed that beta-LPA had no significant inhibitory effects on HBsAg and HBeAg. beta-LPA didn't show any cytotoxicity up to 0.4 microM with a 50% cytotoxic concentration (CC(50)) of 50 microM. Furthermore, treatment with beta-LPA resulted in no apparent inhibitory effects on mitochondrial DNA content. Considering the potent inhibition of HBV DNA synthesis and no obvious toxicity of beta-LPA, this compound should be further explored for development as an anti-HBV drug.

摘要

慢性乙型肝炎的抗病毒治疗仍然是全球范围内的一个主要临床问题。与拉米夫定一样，核苷类似物已成为抗乙型肝炎病毒（抗HBV）药物研究的焦点。在此，β-LPA是一种新型的2,6-二氨基嘌呤类似物，被发现具有强大的抗HBV活性。在HepG2.2.15细胞系中，通过对分泌型和细胞内游离型HBV DNA的分析确定，β-LPA对HBV的50%有效浓度（EC50）为0.01微摩尔。药物处理培养物中HBV表面抗原（HBsAg）和e抗原（HBeAg）的水平显示，β-LPA对HBsAg和HBeAg没有显著抑制作用。β-LPA在高达0.4微摩尔时未显示任何细胞毒性，其50%细胞毒性浓度（CC50）为50微摩尔。此外，用β-LPA处理对线粒体DNA含量没有明显抑制作用。考虑到β-LPA对HBV DNA合成的强大抑制作用且无明显毒性，该化合物应进一步开发作为一种抗HBV药物。