2'3'-二脱氧腺苷（DDA）和3'-叠氮基-3'-脱氧胸苷（AZT）的疏水氨基酸磷酸酰胺单酯的抗病毒活性比较。

Comparison of the antiviral activity of hydrophobic amino acid phosphoramidate monoesters of 2'3'-dideoxyadenosine (DDA) and 3'-azido-3'-deoxythymidine (AZT).

作者信息

Chang S L, Griesgraber G, Wagner C R

机构信息

Department of Medicinal Chemistry, University of Minnesota, Minneapolis 55455, USA.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2001 Aug;20(8):1571-82. doi: 10.1081/NCN-100105248.

DOI:10.1081/NCN-100105248

PMID:11554546

Abstract

A series of hydrophobic, water soluble and non-toxic amino acid phosphoramidate monoesters of dideoxyadenosine (ddA) and 3'-azido-3'-deoxythymidine were shown to inhibit the replication of HIV-1 in human peripheral blood mononuclear cells (PBMC) from two donors. The tryptophan methyl ester phosphoramidates of AZT and ddA were equally potent (EC50S = 0.3-0.4 microM), while the phenyl methyl ester of ddA was 40- to 100- fold more potent than the AZT derivatives. The alaninyl methyl ester of AZT was found to be 70- fold more potent than the ddA derivative. The methyl amide derivatives were found to be 5-20 fold less active than the methyl esters for the ddA series, while for AZT the derivatives were found to be of similar potency or 60- to 166- fold more potent than the methylesters.

摘要

一系列疏水、水溶性且无毒的双脱氧腺苷（ddA）和3'-叠氮基-3'-脱氧胸苷的氨基酸磷酸酰胺单酯被证明可抑制来自两名供体的人外周血单核细胞（PBMC）中HIV-1的复制。AZT和ddA的色氨酸甲酯磷酸酰胺具有同等效力（EC50 = 0.3 - 0.4 microM），而ddA的苯甲酯效力比AZT衍生物高40至100倍。发现AZT的丙氨酰甲酯比ddA衍生物效力高70倍。对于ddA系列，发现甲基酰胺衍生物的活性比甲酯低5至20倍，而对于AZT，发现这些衍生物效力相似或比甲酯高60至166倍。