Synthesis of azide derivative and discovery of glyoxalase pathway inhibitor against pathogenic bacteria

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Abstract

A glyoxalase inhibitor was synthesized and tested against Staphylococcus aureus for first time and showed MIC90 of 20 μg/ml. Henceforth, we synthesized unnatural azide derivative of the same inhibitor to improve the biological activity. In that order, an azide carboxylate was synthesized from dimethyl tartrate by tosylation and azide substitution. The synthesized, azide compound was coupled with glutathione derivative in high yield and tested against S. aureus and showed improved MIC90 of 5 μg/ml. In general, it can be also easily converted to unnatural β-amino acid in good yield. The shown methodology will be extended to study induced suicide in Burkholderia mallei, Francisella tularensis and Mycobacterium tuberculosis in future.

Original languageEnglish (US)
Pages (from-to)6138-6140
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number22
DOIs
StatePublished - Nov 15 2013

Fingerprint

Azides
Bacteria
Derivatives
Staphylococcus aureus
Burkholderia mallei
Francisella tularensis
Bioactivity
Mycobacterium tuberculosis
Suicide
Glutathione
Substitution reactions
Amino Acids

Keywords

  • Glutathione derivative
  • Glyoxalase pathway
  • Inhibitor
  • Metabolism
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

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title = "Synthesis of azide derivative and discovery of glyoxalase pathway inhibitor against pathogenic bacteria",
abstract = "A glyoxalase inhibitor was synthesized and tested against Staphylococcus aureus for first time and showed MIC90 of 20 μg/ml. Henceforth, we synthesized unnatural azide derivative of the same inhibitor to improve the biological activity. In that order, an azide carboxylate was synthesized from dimethyl tartrate by tosylation and azide substitution. The synthesized, azide compound was coupled with glutathione derivative in high yield and tested against S. aureus and showed improved MIC90 of 5 μg/ml. In general, it can be also easily converted to unnatural β-amino acid in good yield. The shown methodology will be extended to study induced suicide in Burkholderia mallei, Francisella tularensis and Mycobacterium tuberculosis in future.",
keywords = "Glutathione derivative, Glyoxalase pathway, Inhibitor, Metabolism, Staphylococcus aureus",
author = "Edagwa, {Benson J} and Yiran Wang and Prabagaran Narayanasamy",
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AU - Edagwa, Benson J

AU - Wang, Yiran

AU - Narayanasamy, Prabagaran

PY - 2013/11/15

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N2 - A glyoxalase inhibitor was synthesized and tested against Staphylococcus aureus for first time and showed MIC90 of 20 μg/ml. Henceforth, we synthesized unnatural azide derivative of the same inhibitor to improve the biological activity. In that order, an azide carboxylate was synthesized from dimethyl tartrate by tosylation and azide substitution. The synthesized, azide compound was coupled with glutathione derivative in high yield and tested against S. aureus and showed improved MIC90 of 5 μg/ml. In general, it can be also easily converted to unnatural β-amino acid in good yield. The shown methodology will be extended to study induced suicide in Burkholderia mallei, Francisella tularensis and Mycobacterium tuberculosis in future.

AB - A glyoxalase inhibitor was synthesized and tested against Staphylococcus aureus for first time and showed MIC90 of 20 μg/ml. Henceforth, we synthesized unnatural azide derivative of the same inhibitor to improve the biological activity. In that order, an azide carboxylate was synthesized from dimethyl tartrate by tosylation and azide substitution. The synthesized, azide compound was coupled with glutathione derivative in high yield and tested against S. aureus and showed improved MIC90 of 5 μg/ml. In general, it can be also easily converted to unnatural β-amino acid in good yield. The shown methodology will be extended to study induced suicide in Burkholderia mallei, Francisella tularensis and Mycobacterium tuberculosis in future.

KW - Glutathione derivative

KW - Glyoxalase pathway

KW - Inhibitor

KW - Metabolism

KW - Staphylococcus aureus

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