Synthesis and Antimycobacterial Activity of 3-Phenyl-1<i>H</i>-indoles

Synthesis and Antimycobacterial Activity of 3-Phenyl-1<i>H</i>-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 1<i>H</i>-indoles were synthesized and evaluated as in vitro inhibitors of <i>Mycobacterium tuberculosis</i> (Mtb) growth....

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Main Authors: Renata Jardim Etchart, Raoní S. Rambo, Bruno Lopes Abbadi, Nathalia Sperotto, Christiano Ev Neves, Fernanda Fries Silva, Maiele Dornelles, Lovaine Duarte, Fernanda Souza Macchi, Marcia Alberton Perelló, Rogério Vescia Lourega, Cristiano Valim Bizarro, Luiz Augusto Basso, Pablo Machado
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Molecules
Subjects:
1<i>H</i>-indoles
<i>Mycobacterium tuberculosis</i>
mammalian cellular viability
genotoxicity
time-kill
pharmacodynamic model
Online Access:https://www.mdpi.com/1420-3049/26/17/5148
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author Renata Jardim Etchart
Raoní S. Rambo
Bruno Lopes Abbadi
Nathalia Sperotto
Christiano Ev Neves
Fernanda Fries Silva
Maiele Dornelles
Lovaine Duarte
Fernanda Souza Macchi
Marcia Alberton Perelló
Rogério Vescia Lourega
Cristiano Valim Bizarro
Luiz Augusto Basso
Pablo Machado
spellingShingle Renata Jardim Etchart
Raoní S. Rambo
Bruno Lopes Abbadi
Nathalia Sperotto
Christiano Ev Neves
Fernanda Fries Silva
Maiele Dornelles
Lovaine Duarte
Fernanda Souza Macchi
Marcia Alberton Perelló
Rogério Vescia Lourega
Cristiano Valim Bizarro
Luiz Augusto Basso
Pablo Machado
Synthesis and Antimycobacterial Activity of 3-Phenyl-1<i>H</i>-indoles
Molecules
1<i>H</i>-indoles
<i>Mycobacterium tuberculosis</i>
mammalian cellular viability
genotoxicity
time-kill
pharmacodynamic model
author_facet Renata Jardim Etchart
Raoní S. Rambo
Bruno Lopes Abbadi
Nathalia Sperotto
Christiano Ev Neves
Fernanda Fries Silva
Maiele Dornelles
Lovaine Duarte
Fernanda Souza Macchi
Marcia Alberton Perelló
Rogério Vescia Lourega
Cristiano Valim Bizarro
Luiz Augusto Basso
Pablo Machado
author_sort Renata Jardim Etchart
title Synthesis and Antimycobacterial Activity of 3-Phenyl-1<i>H</i>-indoles
title_short Synthesis and Antimycobacterial Activity of 3-Phenyl-1<i>H</i>-indoles
title_full Synthesis and Antimycobacterial Activity of 3-Phenyl-1<i>H</i>-indoles
title_fullStr Synthesis and Antimycobacterial Activity of 3-Phenyl-1<i>H</i>-indoles
title_full_unstemmed Synthesis and Antimycobacterial Activity of 3-Phenyl-1<i>H</i>-indoles
title_sort synthesis and antimycobacterial activity of 3-phenyl-1<i>h</i>-indoles
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2021-08-01
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 1<i>H</i>-indoles were synthesized and evaluated as in vitro inhibitors of <i>Mycobacterium tuberculosis</i> (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-1<i>H</i>-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-1<i>H</i>-indole against Mtb for the first time.
topic 1<i>H</i>-indoles
<i>Mycobacterium tuberculosis</i>
mammalian cellular viability
genotoxicity
time-kill
pharmacodynamic model
url https://www.mdpi.com/1420-3049/26/17/5148
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spelling doaj-f94f651a01614b1b911b4aa908223ee32021-09-09T13:52:51ZengMDPI AGMolecules1420-30492021-08-01265148514810.3390/molecules26175148Synthesis and Antimycobacterial Activity of 3-Phenyl-1<i>H</i>-indolesRenata Jardim Etchart0Raoní S. Rambo1Bruno Lopes Abbadi2Nathalia Sperotto3Christiano Ev Neves4Fernanda Fries Silva5Maiele Dornelles6Lovaine Duarte7Fernanda Souza Macchi8Marcia Alberton Perelló9Rogério Vescia Lourega10Cristiano Valim Bizarro11Luiz Augusto Basso12Pablo Machado13Centro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilInstituto de Química, Departamento de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilCentro de Pesquisas em Biologia Molecular e Funcional, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681-Prédio 92A, Porto Alegre 90616-900, RS, BrazilTuberculosis 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 1<i>H</i>-indoles were synthesized and evaluated as in vitro inhibitors of <i>Mycobacterium tuberculosis</i> (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-1<i>H</i>-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-1<i>H</i>-indole against Mtb for the first time.https://www.mdpi.com/1420-3049/26/17/51481<i>H</i>-indoles<i>Mycobacterium tuberculosis</i>mammalian cellular viabilitygenotoxicitytime-killpharmacodynamic model

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