Synthesis and antiviral activity of amino acid carbamate derivatives of AZT

Shu Ling Chang; George Griesgraber; Timothy W. Abraham; Tullika Garg; Heng Song; Cheryl L. Zimmerman; Carston R. Wagner

doi:10.1080/15257770008032998

Synthesis and antiviral activity of amino acid carbamate derivatives of AZT

Shu Ling Chang, George Griesgraber, Timothy W. Abraham, Tullika Garg, Heng Song, Cheryl L. Zimmerman, Carston R. Wagner

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

8 Scopus citations

Abstract

Lipophilic amino acid methyl ester and methyl amide carbamates of 3'- azido-3'-deoxythymidine (AZT) were synthesized and their anti-HIV-1 activity in PBMCs was determined. The methyl amides were more potent (EC₅₀s = 1.8 - 4.0 μM) than the methyl esters (EC₅₀s = 2.0 - 20 μM). Carbamate hydrolysis by cell lysates and liberation of AZT was not observed for representative methyl ester or methyl amide AZT carbamates. No evidence of direct inhibition of HIV reverse transcriptase or integrase was observed.

Original language	English (US)
Pages (from-to)	87-100
Number of pages	14
Journal	Nucleosides, Nucleotides and Nucleic Acids
Volume	19
Issue number	1-2
DOIs	https://doi.org/10.1080/15257770008032998
State	Published - 2000

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Biochemistry
Molecular Medicine
Genetics

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/15257770008032998

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title = "Synthesis and antiviral activity of amino acid carbamate derivatives of AZT",

abstract = "Lipophilic amino acid methyl ester and methyl amide carbamates of 3'- azido-3'-deoxythymidine (AZT) were synthesized and their anti-HIV-1 activity in PBMCs was determined. The methyl amides were more potent (EC50s = 1.8 - 4.0 μM) than the methyl esters (EC50s = 2.0 - 20 μM). Carbamate hydrolysis by cell lysates and liberation of AZT was not observed for representative methyl ester or methyl amide AZT carbamates. No evidence of direct inhibition of HIV reverse transcriptase or integrase was observed.",

author = "Chang, {Shu Ling} and George Griesgraber and Abraham, {Timothy W.} and Tullika Garg and Heng Song and Zimmerman, {Cheryl L.} and Wagner, {Carston R.}",

note = "Funding Information: Partial financial support is gratefully acknowledged from NIH (CA61908), Advanced Magnetics, Inc., and the University of Mmnesota Graduate School. We also wish to thank Dr. Christophe Marchand and Dr. Yves Pommier of the National Institutes of Health for carrying out the integrase inhibition assays.",

year = "2000",

doi = "10.1080/15257770008032998",

language = "English (US)",

volume = "19",

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T1 - Synthesis and antiviral activity of amino acid carbamate derivatives of AZT

AU - Chang, Shu Ling

AU - Griesgraber, George

AU - Abraham, Timothy W.

AU - Garg, Tullika

AU - Song, Heng

AU - Zimmerman, Cheryl L.

AU - Wagner, Carston R.

N1 - Funding Information: Partial financial support is gratefully acknowledged from NIH (CA61908), Advanced Magnetics, Inc., and the University of Mmnesota Graduate School. We also wish to thank Dr. Christophe Marchand and Dr. Yves Pommier of the National Institutes of Health for carrying out the integrase inhibition assays.

PY - 2000

Y1 - 2000

N2 - Lipophilic amino acid methyl ester and methyl amide carbamates of 3'- azido-3'-deoxythymidine (AZT) were synthesized and their anti-HIV-1 activity in PBMCs was determined. The methyl amides were more potent (EC50s = 1.8 - 4.0 μM) than the methyl esters (EC50s = 2.0 - 20 μM). Carbamate hydrolysis by cell lysates and liberation of AZT was not observed for representative methyl ester or methyl amide AZT carbamates. No evidence of direct inhibition of HIV reverse transcriptase or integrase was observed.

AB - Lipophilic amino acid methyl ester and methyl amide carbamates of 3'- azido-3'-deoxythymidine (AZT) were synthesized and their anti-HIV-1 activity in PBMCs was determined. The methyl amides were more potent (EC50s = 1.8 - 4.0 μM) than the methyl esters (EC50s = 2.0 - 20 μM). Carbamate hydrolysis by cell lysates and liberation of AZT was not observed for representative methyl ester or methyl amide AZT carbamates. No evidence of direct inhibition of HIV reverse transcriptase or integrase was observed.

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Synthesis and antiviral activity of amino acid carbamate derivatives of AZT

Abstract

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