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Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3
Bacterial cystathionine γ-lyase (bCSE) is the main producer of H(2)S in pathogenic bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, etc. The suppression of bCSE activity considerably enhances the sensitivity of bacteria to antibiotics. Convenient methods for the efficient synthesis of...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147042/ https://www.ncbi.nlm.nih.gov/pubmed/37110802 http://dx.doi.org/10.3390/molecules28083568 |
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author | Potapov, Konstantin V. Novikov, Roman A. Novikov, Maxim A. Solyev, Pavel N. Tomilov, Yury V. Kochetkov, Sergey N. Makarov, Alexander A. Mitkevich, Vladimir A. |
author_facet | Potapov, Konstantin V. Novikov, Roman A. Novikov, Maxim A. Solyev, Pavel N. Tomilov, Yury V. Kochetkov, Sergey N. Makarov, Alexander A. Mitkevich, Vladimir A. |
author_sort | Potapov, Konstantin V. |
collection | PubMed |
description | Bacterial cystathionine γ-lyase (bCSE) is the main producer of H(2)S in pathogenic bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, etc. The suppression of bCSE activity considerably enhances the sensitivity of bacteria to antibiotics. Convenient methods for the efficient synthesis of gram quantities of two selective indole-based bCSE inhibitors, namely (2-(6-bromo-1H-indol-1-yl)acetyl)glycine (NL1), 5-((6-bromo-1H-indol-1-yl)methyl)- 2-methylfuran-3-carboxylic acid (NL2), as well as a synthetic method for preparation 3-((6-(7-chlorobenzo[b]thiophen-2-yl)-1H-indol-1-yl)methyl)- 1H-pyrazole-5-carboxylic acid (NL3), have been developed. The syntheses are based on the use of 6-bromoindole as the main building block for all three inhibitors (NL1, NL2, and NL3), and the designed residues are assembled at the nitrogen atom of the 6-bromoindole core or by the substitution of the bromine atom in the case of NL3 using Pd-catalyzed cross-coupling. The developed and refined synthetic methods would be significant for the further biological screening of NL-series bCSE inhibitors and their derivatives. |
format | Online Article Text |
id | pubmed-10147042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101470422023-04-29 Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3 Potapov, Konstantin V. Novikov, Roman A. Novikov, Maxim A. Solyev, Pavel N. Tomilov, Yury V. Kochetkov, Sergey N. Makarov, Alexander A. Mitkevich, Vladimir A. Molecules Article Bacterial cystathionine γ-lyase (bCSE) is the main producer of H(2)S in pathogenic bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, etc. The suppression of bCSE activity considerably enhances the sensitivity of bacteria to antibiotics. Convenient methods for the efficient synthesis of gram quantities of two selective indole-based bCSE inhibitors, namely (2-(6-bromo-1H-indol-1-yl)acetyl)glycine (NL1), 5-((6-bromo-1H-indol-1-yl)methyl)- 2-methylfuran-3-carboxylic acid (NL2), as well as a synthetic method for preparation 3-((6-(7-chlorobenzo[b]thiophen-2-yl)-1H-indol-1-yl)methyl)- 1H-pyrazole-5-carboxylic acid (NL3), have been developed. The syntheses are based on the use of 6-bromoindole as the main building block for all three inhibitors (NL1, NL2, and NL3), and the designed residues are assembled at the nitrogen atom of the 6-bromoindole core or by the substitution of the bromine atom in the case of NL3 using Pd-catalyzed cross-coupling. The developed and refined synthetic methods would be significant for the further biological screening of NL-series bCSE inhibitors and their derivatives. MDPI 2023-04-19 /pmc/articles/PMC10147042/ /pubmed/37110802 http://dx.doi.org/10.3390/molecules28083568 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Potapov, Konstantin V. Novikov, Roman A. Novikov, Maxim A. Solyev, Pavel N. Tomilov, Yury V. Kochetkov, Sergey N. Makarov, Alexander A. Mitkevich, Vladimir A. Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3 |
title | Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3 |
title_full | Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3 |
title_fullStr | Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3 |
title_full_unstemmed | Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3 |
title_short | Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3 |
title_sort | synthesis of the indole-based inhibitors of bacterial cystathionine γ-lyase nl1-nl3 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147042/ https://www.ncbi.nlm.nih.gov/pubmed/37110802 http://dx.doi.org/10.3390/molecules28083568 |
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