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Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies

We prepared a series of substituted N-(pyrazin-2-yl)benzenesulfonamides as an attempt to investigate the effect of different linkers connecting pyrazine to benzene cores on antimicrobial activity when compared to our previous compounds of amide or retro-amide linker type. Only two compounds, 4-amino...

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Autores principales: Bouz, Ghada, Juhás, Martin, Pausas Otero, Lluis, Paredes de la Red, Cristina, Janďourek, Ondřej, Konečná, Klára, Paterová, Pavla, Kubíček, Vladimír, Janoušek, Jiří, Doležal, Martin, Zitko, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982817/
https://www.ncbi.nlm.nih.gov/pubmed/31905775
http://dx.doi.org/10.3390/molecules25010138
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author Bouz, Ghada
Juhás, Martin
Pausas Otero, Lluis
Paredes de la Red, Cristina
Janďourek, Ondřej
Konečná, Klára
Paterová, Pavla
Kubíček, Vladimír
Janoušek, Jiří
Doležal, Martin
Zitko, Jan
author_facet Bouz, Ghada
Juhás, Martin
Pausas Otero, Lluis
Paredes de la Red, Cristina
Janďourek, Ondřej
Konečná, Klára
Paterová, Pavla
Kubíček, Vladimír
Janoušek, Jiří
Doležal, Martin
Zitko, Jan
author_sort Bouz, Ghada
collection PubMed
description We prepared a series of substituted N-(pyrazin-2-yl)benzenesulfonamides as an attempt to investigate the effect of different linkers connecting pyrazine to benzene cores on antimicrobial activity when compared to our previous compounds of amide or retro-amide linker type. Only two compounds, 4-amino-N-(pyrazin-2-yl)benzenesulfonamide (MIC = 6.25 μg/mL, 25 μM) and 4-amino-N-(6-chloropyrazin-2-yl)benzenesulfonamide (MIC = 6.25 μg/mL, 22 μM) exerted good antitubercular activity against M. tuberculosis H37Rv. However, they were excluded from the comparison as they—unlike the other compounds—possessed the pharmacophore for the inhibition of folate pathway, which was proven by docking studies. We performed target fishing, where we identified matrix metalloproteinase-8 as a promising target for our title compounds that is worth future exploration.
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spelling pubmed-69828172020-02-06 Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies Bouz, Ghada Juhás, Martin Pausas Otero, Lluis Paredes de la Red, Cristina Janďourek, Ondřej Konečná, Klára Paterová, Pavla Kubíček, Vladimír Janoušek, Jiří Doležal, Martin Zitko, Jan Molecules Article We prepared a series of substituted N-(pyrazin-2-yl)benzenesulfonamides as an attempt to investigate the effect of different linkers connecting pyrazine to benzene cores on antimicrobial activity when compared to our previous compounds of amide or retro-amide linker type. Only two compounds, 4-amino-N-(pyrazin-2-yl)benzenesulfonamide (MIC = 6.25 μg/mL, 25 μM) and 4-amino-N-(6-chloropyrazin-2-yl)benzenesulfonamide (MIC = 6.25 μg/mL, 22 μM) exerted good antitubercular activity against M. tuberculosis H37Rv. However, they were excluded from the comparison as they—unlike the other compounds—possessed the pharmacophore for the inhibition of folate pathway, which was proven by docking studies. We performed target fishing, where we identified matrix metalloproteinase-8 as a promising target for our title compounds that is worth future exploration. MDPI 2019-12-29 /pmc/articles/PMC6982817/ /pubmed/31905775 http://dx.doi.org/10.3390/molecules25010138 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bouz, Ghada
Juhás, Martin
Pausas Otero, Lluis
Paredes de la Red, Cristina
Janďourek, Ondřej
Konečná, Klára
Paterová, Pavla
Kubíček, Vladimír
Janoušek, Jiří
Doležal, Martin
Zitko, Jan
Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies
title Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies
title_full Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies
title_fullStr Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies
title_full_unstemmed Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies
title_short Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies
title_sort substituted n-(pyrazin-2-yl)benzenesulfonamides; synthesis, anti-infective evaluation, cytotoxicity, and in silico studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982817/
https://www.ncbi.nlm.nih.gov/pubmed/31905775
http://dx.doi.org/10.3390/molecules25010138
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