抗HIV药物AZT前药的合成和抗病毒活性的初步研究  

Synthesis and preliminary evaluation of anti-HIV agent AZT prodrug

作　　者：崔庆彬[1] 张高小[1] 于沛[1] 王玉强[1] 

机构地区：[1]暨南大学药学院新药研究所,广东广州510632

出　　处：《药学学报》2011年第8期1015-1018,共4页Acta Pharmaceutica Sinica

摘　　要：In this research,phosphate and thiophosphate prodrugs 3a,3b of anti-HIV agent AZT were synthesized,and their anti-HIV activities and cytotoxicities were investigated in vitro.Results showed that the prodrugs 3a and 3b with an IC50 value of 11.0 and 4.0 μmol-L-1,respectively,were less toxic than AZT(1.0 μmol-L-1).Although the EC50 values of both 3a(0.04 μmol-L-1) and 3b(0.16 μmol-L-1) were lower than that of AZT(0.01 μmol-L-1),the therapeutic index(IC50/EC50) of prodrug 3a(275) was much higher than that of both AZT(100) and prodrug 3b(25).This indicated that the prodrug 3a merited further investigation as an anti-HIV agent.In this research,phosphate and thiophosphate prodrugs 3a,3b of anti-HIV agent AZT were synthesized,and their anti-HIV activities and cytotoxicities were investigated in vitro.Results showed that the prodrugs 3a and 3b with an IC50 value of 11.0 and 4.0 μmol-L-1,respectively,were less toxic than AZT（1.0 μmol-L-1）.Although the EC50 values of both 3a（0.04 μmol-L-1） and 3b（0.16 μmol-L-1） were lower than that of AZT（0.01 μmol-L-1）,the therapeutic index（IC50/EC50） of prodrug 3a（275） was much higher than that of both AZT（100） and prodrug 3b（25）.This indicated that the prodrug 3a merited further investigation as an anti-HIV agent.

关 键 词：核苷类似物 叠氮胸苷 前药 抗HIV 

分 类 号：R916[医药卫生—药学]