4-氨基酸取代嘧啶核苷类化合物的抗HBV活性研究
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摘要：
以野生型乙型肝炎病毒(HBV)细胞株HepG2.2.15和拉米夫定耐药型HBV细胞株HepGRL1为模型,分别采用酶联免疫吸附检测(ELISA)法测定4-氨基酸取代嘧啶核苷类化合物(GY001-GY005)对乙型肝炎e抗原(HBeAg)和乙型肝炎表面抗原(HBsAg)的影响,四甲基偶氮唑蓝(MTT)法测定4-氨基酸取代嘧啶核苷类化合物(GY001-GY005)对HepG2细胞的毒性,实时荧光定量聚合酶链反应(FQ-PCR)法检测4-氨基酸取代嘧啶核苷类化合物(GY001-GY005)对细胞上清液中和胞内HBV DNA拷贝数的影响.结果显示,在HepG2.2.15细胞和HepGRL1细胞中,GY001,GY002,GY003,GY004,GY005对细胞上清和细胞内HBV DNA均有非常好的抑制作用,效果优于拉米夫定(3TC),且没有表现出明显的耐药性;GY001,GY002,GY003,GY004,GY005对HepG2细胞的毒性均较小,其中GY002和GY005的半数细胞毒性浓度(CC 50)>1000μmol/L,GY001和GY003的CC 50分别为963.69μmol/L和994.49μmol/L,GY004的毒性相比稍大,CC 50为545.12μmol/L.
HepG2.2.15 cells transfected with wild-type hepatitis B virus HBV cellar and HepGRL1 cells transfected with lamivudine-resistant HBV were used as experimental cells.The effects of 4-amino acid substituted pyrimidine nucleosides(GY001-GY005)on hepatitis B e antigen(HBeAg)and Hepatitis B surface antigen(HBsAg)were detected by enzyme linked immunosorbent assay(ELISA).The toxicity of 4-amino acid substituted pyrimidine nucleosides(GY001-GY005)on HepG2 cells was determined by tetramethylazo blue(MTT)method,and the effects of 4-amino acid substituted pyrimidine nucleosides(GY001-GY005)on HBV DNA copy number in cell supernatant and in cell were detected by FQ-PCR.The results showed that in HepG2.2.15 cells and HepGRL1 cells,GY001,GY002,GY003,GY004,GY005 had very good inhibitory effect on HBV DNA in cell supernatant and cell,and the effect was better than that of 3TC,showing no obvious drug resistance;GY001,GY002,GY003,GY004,GY005 had less toxicity to HepG2 cells,and the median cytotoxic concentration(CC 50)of GY002 and GY005 was more than 1000.The CC 50 of GY001 and GY003 were 963.69μmol/L and 994.49μmol/L,respectively.The toxicity of GY004 was slightly higher,and the CC 50 was 545.12μmol/L.
作者：
郭晓河 陈亚娟 李玉江 陶乐 董黎红 王强 常俊标
Guo Xiaohe;Chen Yajuan;Li Yujiang;Tao Le;Dong Lihong;Wang Qiang;Chang Junbiao(High&New Technology Research Center,Henan Academy of Sciences,Zhengzhou 475001,China;School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China;School of Chemistry and Chemical Engineering,Henan Normal University,Xinxiang 453007,China)
机构地区：
河南省科学院高新技术研究中心 郑州大学药学院 betway官方app 化学化工学院
出处：
《betway官方app 学报：自然科学版》 CAS 北大核心 2021年第4期82-89,共8页
基金：
河南省科技创新杰出青年基金(094100510019) 河南省基础与前沿技术研究项目(162300410006) 河南省科技攻关计划项目(092102310021) 河南省科学院基本科研费项目(200602007).
关键词：
4-氨基酸取代 嘧啶核苷化合物 抗HBV活性
4-amino acid substituted pyrimidine nucleoside compounds anti HBV activity
分类号：
O626 [理学—有机化学]
