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Synthesis and Antimycobacterial Activity of 3-Phenyl-1H-indoles

Tuberculosis has been described as a global health crisis since the 1990s, with an estimated 1.4 million deaths in the last year. Herein, a series of 20 1H-indoles were synthesized and evaluated as in vitro inhibitors of Mycobacterium tuberculosis (Mtb) growth. Furthermore, the top hit compounds wer...

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Autores principales: Jardim Etchart, Renata, Rambo, Raoní S., Lopes Abbadi, Bruno, Sperotto, Nathalia, Ev Neves, Christiano, Fries Silva, Fernanda, Dornelles, Maiele, Duarte, Lovaine, Souza Macchi, Fernanda, Alberton Perelló, Marcia, Vescia Lourega, Rogério, Valim Bizarro, Cristiano, Basso, Luiz Augusto, Machado, Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433792/
https://www.ncbi.nlm.nih.gov/pubmed/34500579
http://dx.doi.org/10.3390/molecules26175148
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author Jardim Etchart, Renata
Rambo, Raoní S.
Lopes Abbadi, Bruno
Sperotto, Nathalia
Ev Neves, Christiano
Fries Silva, Fernanda
Dornelles, Maiele
Duarte, Lovaine
Souza Macchi, Fernanda
Alberton Perelló, Marcia
Vescia Lourega, Rogério
Valim Bizarro, Cristiano
Basso, Luiz Augusto
Machado, Pablo
author_facet Jardim Etchart, Renata
Rambo, Raoní S.
Lopes Abbadi, Bruno
Sperotto, Nathalia
Ev Neves, Christiano
Fries Silva, Fernanda
Dornelles, Maiele
Duarte, Lovaine
Souza Macchi, Fernanda
Alberton Perelló, Marcia
Vescia Lourega, Rogério
Valim Bizarro, Cristiano
Basso, Luiz Augusto
Machado, Pablo
author_sort Jardim Etchart, Renata
collection PubMed
description Tuberculosis has been described as a global health crisis since the 1990s, with an estimated 1.4 million deaths in the last year. Herein, a series of 20 1H-indoles were synthesized and evaluated as in vitro inhibitors of Mycobacterium tuberculosis (Mtb) growth. Furthermore, the top hit compounds were active against multidrug-resistant strains, without cross-resistance with first-line drugs. Exposing HepG2 and Vero cells to the molecules for 72 h showed that one of the evaluated structures was devoid of apparent toxicity. In addition, this 3-phenyl-1H-indole showed no genotoxicity signals. Finally, time-kill and pharmacodynamic model analyses demonstrated that this compound has bactericidal activity at concentrations close to the Minimum Inhibitory Concentration, coupled with a strong time-dependent behavior. To the best of our knowledge, this study describes the activity of 3-phenyl-1H-indole against Mtb for the first time.
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spelling pubmed-84337922021-09-12 Synthesis and Antimycobacterial Activity of 3-Phenyl-1H-indoles Jardim Etchart, Renata Rambo, Raoní S. Lopes Abbadi, Bruno Sperotto, Nathalia Ev Neves, Christiano Fries Silva, Fernanda Dornelles, Maiele Duarte, Lovaine Souza Macchi, Fernanda Alberton Perelló, Marcia Vescia Lourega, Rogério Valim Bizarro, Cristiano Basso, Luiz Augusto Machado, Pablo Molecules Article Tuberculosis has been described as a global health crisis since the 1990s, with an estimated 1.4 million deaths in the last year. Herein, a series of 20 1H-indoles were synthesized and evaluated as in vitro inhibitors of Mycobacterium tuberculosis (Mtb) growth. Furthermore, the top hit compounds were active against multidrug-resistant strains, without cross-resistance with first-line drugs. Exposing HepG2 and Vero cells to the molecules for 72 h showed that one of the evaluated structures was devoid of apparent toxicity. In addition, this 3-phenyl-1H-indole showed no genotoxicity signals. Finally, time-kill and pharmacodynamic model analyses demonstrated that this compound has bactericidal activity at concentrations close to the Minimum Inhibitory Concentration, coupled with a strong time-dependent behavior. To the best of our knowledge, this study describes the activity of 3-phenyl-1H-indole against Mtb for the first time. MDPI 2021-08-25 /pmc/articles/PMC8433792/ /pubmed/34500579 http://dx.doi.org/10.3390/molecules26175148 Text en © 2021 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
Jardim Etchart, Renata
Rambo, Raoní S.
Lopes Abbadi, Bruno
Sperotto, Nathalia
Ev Neves, Christiano
Fries Silva, Fernanda
Dornelles, Maiele
Duarte, Lovaine
Souza Macchi, Fernanda
Alberton Perelló, Marcia
Vescia Lourega, Rogério
Valim Bizarro, Cristiano
Basso, Luiz Augusto
Machado, Pablo
Synthesis and Antimycobacterial Activity of 3-Phenyl-1H-indoles
title Synthesis and Antimycobacterial Activity of 3-Phenyl-1H-indoles
title_full Synthesis and Antimycobacterial Activity of 3-Phenyl-1H-indoles
title_fullStr Synthesis and Antimycobacterial Activity of 3-Phenyl-1H-indoles
title_full_unstemmed Synthesis and Antimycobacterial Activity of 3-Phenyl-1H-indoles
title_short Synthesis and Antimycobacterial Activity of 3-Phenyl-1H-indoles
title_sort synthesis and antimycobacterial activity of 3-phenyl-1h-indoles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433792/
https://www.ncbi.nlm.nih.gov/pubmed/34500579
http://dx.doi.org/10.3390/molecules26175148
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