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

Shu Ling Chang, George Griesgraber, Carston R Wagner

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 μM), 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.

Original languageEnglish (US)
Pages (from-to)1571-1582
Number of pages12
JournalNucleosides, Nucleotides and Nucleic Acids
Volume20
Issue number8
DOIs
StatePublished - Jan 1 2001

Fingerprint

Dideoxyadenosine
Zidovudine
Antiviral Agents
Amino Acids
Derivatives
Esters
Amides
HIV-1
Blood Cells
Blood
phosphoramidic acid
Water

Cite this

@article{99e2097c8f3c45ed8f134fd81d81f9cd,
title = "Comparison of the antiviral activity of hydrophobic amino acid phosphoramidate monoesters of 2′,3′-dideoxyadenosine (DDA) and 3′-azido-3′-deoxythymidine (AZT)",
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 μM), 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.",
author = "Chang, {Shu Ling} and George Griesgraber and Wagner, {Carston R}",
year = "2001",
month = "1",
day = "1",
doi = "10.1081/NCN-100105248",
language = "English (US)",
volume = "20",
pages = "1571--1582",
journal = "Nucleosides and Nucleotides",
issn = "0732-8311",
publisher = "Taylor and Francis Ltd.",
number = "8",

}

TY - JOUR

T1 - Comparison of the antiviral activity of hydrophobic amino acid phosphoramidate monoesters of 2′,3′-dideoxyadenosine (DDA) and 3′-azido-3′-deoxythymidine (AZT)

AU - Chang, Shu Ling

AU - Griesgraber, George

AU - Wagner, Carston R

PY - 2001/1/1

Y1 - 2001/1/1

N2 - 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 μM), 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.

AB - 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 μM), 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.

UR - http://www.scopus.com/inward/record.url?scp=0034869668&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034869668&partnerID=8YFLogxK

U2 - 10.1081/NCN-100105248

DO - 10.1081/NCN-100105248

M3 - Article

C2 - 11554546

AN - SCOPUS:0034869668

VL - 20

SP - 1571

EP - 1582

JO - Nucleosides and Nucleotides

JF - Nucleosides and Nucleotides

SN - 0732-8311

IS - 8

ER -