Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents

RNA viral infections, including those caused by respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Venezuelan Equine encephalitis virus (VEEV), pose a major global health challenge. Here, we report the synthesis and screening of a series of pyrrolo[2...

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Autores principales: Martinez-Gualda, Belén, Graus, Mirthe, Camps, Anita, Vanhulle, Emiel, Saul, Sirle, Azari, Siavash, Nhu Tran, Do Hoang, Vangeel, Laura, Chiu, Winston, Neyts, Johan, Schols, Dominique, Einav, Shirit, Vermeire, Kurt, De Jonghe, Steven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643853/
https://www.ncbi.nlm.nih.gov/pubmed/36385995
http://dx.doi.org/10.3389/fchem.2022.1058229
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author Martinez-Gualda, Belén
Graus, Mirthe
Camps, Anita
Vanhulle, Emiel
Saul, Sirle
Azari, Siavash
Nhu Tran, Do Hoang
Vangeel, Laura
Chiu, Winston
Neyts, Johan
Schols, Dominique
Einav, Shirit
Vermeire, Kurt
De Jonghe, Steven
author_facet Martinez-Gualda, Belén
Graus, Mirthe
Camps, Anita
Vanhulle, Emiel
Saul, Sirle
Azari, Siavash
Nhu Tran, Do Hoang
Vangeel, Laura
Chiu, Winston
Neyts, Johan
Schols, Dominique
Einav, Shirit
Vermeire, Kurt
De Jonghe, Steven
author_sort Martinez-Gualda, Belén
collection PubMed
description RNA viral infections, including those caused by respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Venezuelan Equine encephalitis virus (VEEV), pose a major global health challenge. Here, we report the synthesis and screening of a series of pyrrolo[2,3-b]pyridines targeting RSV, SARS-CoV-2 and/or VEEV. From this campaign, a series of lead compounds was generated that demonstrated antiviral activity in the low single-digit micromolar range against the various viruses and did not show cytotoxicity. These findings highlight the potential of 3-alkynyl-5-aryl-7-aza-indoles as a promising chemotype for the development of broad-spectrum antiviral agents.
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spelling pubmed-96438532022-11-15 Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents Martinez-Gualda, Belén Graus, Mirthe Camps, Anita Vanhulle, Emiel Saul, Sirle Azari, Siavash Nhu Tran, Do Hoang Vangeel, Laura Chiu, Winston Neyts, Johan Schols, Dominique Einav, Shirit Vermeire, Kurt De Jonghe, Steven Front Chem Chemistry RNA viral infections, including those caused by respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Venezuelan Equine encephalitis virus (VEEV), pose a major global health challenge. Here, we report the synthesis and screening of a series of pyrrolo[2,3-b]pyridines targeting RSV, SARS-CoV-2 and/or VEEV. From this campaign, a series of lead compounds was generated that demonstrated antiviral activity in the low single-digit micromolar range against the various viruses and did not show cytotoxicity. These findings highlight the potential of 3-alkynyl-5-aryl-7-aza-indoles as a promising chemotype for the development of broad-spectrum antiviral agents. Frontiers Media S.A. 2022-10-26 /pmc/articles/PMC9643853/ /pubmed/36385995 http://dx.doi.org/10.3389/fchem.2022.1058229 Text en Copyright © 2022 Martinez-Gualda, Graus, Camps, Vanhulle, Saul, Azari, Nhu Tran, Vangeel, Chiu, Neyts, Schols, Einav, Vermeire and De Jonghe. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Martinez-Gualda, Belén
Graus, Mirthe
Camps, Anita
Vanhulle, Emiel
Saul, Sirle
Azari, Siavash
Nhu Tran, Do Hoang
Vangeel, Laura
Chiu, Winston
Neyts, Johan
Schols, Dominique
Einav, Shirit
Vermeire, Kurt
De Jonghe, Steven
Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents
title Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents
title_full Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents
title_fullStr Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents
title_full_unstemmed Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents
title_short Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents
title_sort synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643853/
https://www.ncbi.nlm.nih.gov/pubmed/36385995
http://dx.doi.org/10.3389/fchem.2022.1058229
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