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

doi:10.1081/NCN-100105248

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

Medicinal Chemistry

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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 language	English (US)
Pages (from-to)	1571-1582
Number of pages	12
Journal	Nucleosides, Nucleotides and Nucleic Acids
Volume	20
Issue number	8
DOIs	https://doi.org/10.1081/NCN-100105248
State	Published - 2001

Bibliographical note

Funding Information:
Partial financial support is gratefully acknowledged from Advanced Magnetics, Inc., and the University of Minnesota Graduate School. We also wish to thank Dr. Jean-Louis Imbach for his kind gift of ddA.

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Comparison of the antiviral activity of hydrophobic amino acid phosphoramidate monoesters of 2′,3′-dideoxyadenosine (DDA) and 3′-azido-3′-deoxythymidine (AZT). / Chang, Shu Ling; Griesgraber, George; Wagner, Carston R.

In: Nucleosides, Nucleotides and Nucleic Acids, Vol. 20, No. 8, 2001, p. 1571-1582.

Research output: Contribution to journal › Article › peer-review

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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.}",

note = "Funding Information: Partial financial support is gratefully acknowledged from Advanced Magnetics, Inc., and the University of Minnesota Graduate School. We also wish to thank Dr. Jean-Louis Imbach for his kind gift of ddA.",

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AU - Griesgraber, George

AU - Wagner, Carston R.

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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.

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

Abstract

Bibliographical note

UN SDGs

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