齐多夫定5'-磷酰氟化物衍生物的合成、抗HIV活性及稳定性研究

Synthesis, anti-HIV activity, and stability studies of 5'-phosphorofluoridate derivatives of AZT.

作者信息

Egron D, Arzumanov A A, Dyatkina N B, Aubertin A M, Imbach J L, Gosselin G, Krayevsky A, Périgaud C

机构信息

UMR CNRS 5625, Université Montpellier II, cc 008, Place E. Bataillon, Montpellier Cedex 5, 34095, France.

出版信息

Bioorg Chem. 2001 Dec;29(6):333-44. doi: 10.1006/bioo.2001.1220.

DOI:10.1006/bioo.2001.1220

PMID:11846432

Abstract

The synthesis, in vitro anti-HIV activity and stability studies of the 5'-fluorophosphate derivative of 3'-azido-3'-deoxythymidine (AZT) are reported. The results support the hypothesis that this phosphorylated entity exerts its biological effect via the delivery of the corresponding 5'-mononucleotide through an enzymatic process. However, the antiviral evaluation in thymidine kinase-deficient CEM cells as well as the stability studies in culture medium and cell extract showed that this bioconversion is not specific to the intracellular medium. Attempts to improve the biological activity of mononucleoside 5'-fluorophosphates by the use of the S-pivaloyl-2-thioethyl (tBuSATE) group as biolabile phosphate protection are reported.

摘要

报道了3'-叠氮基-3'-脱氧胸苷（AZT）的5'-氟磷酸酯衍生物的合成、体外抗HIV活性及稳定性研究。结果支持这样的假说，即该磷酸化实体通过酶促过程传递相应的5'-单核苷酸来发挥其生物学效应。然而，在胸苷激酶缺陷的CEM细胞中的抗病毒评估以及在培养基和细胞提取物中的稳定性研究表明，这种生物转化并非细胞内介质所特有的。报道了尝试通过使用S-新戊酰基-2-硫代乙基（tBuSATE）基团作为生物可裂解的磷酸保护基来提高单核苷5'-氟磷酸酯的生物活性。