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

被引：3

作者：

Etchart, Renata Jardim ^{[1
,2
]}

Rambo, Raoni S. ^{[1
]}

Abbadi, Bruno Lopes ^{[1
]}

Sperotto, Nathalia ^{[1
]}

Neves, Christiano Ev ^{[1
,2
]}

Silva, Fernanda Fries ^{[1
,2
]}

Dornelles, Maiele ^{[1
]}

Duarte, Lovaine ^{[1
]}

Macchi, Fernanda Souza ^{[1
,2
]}

Perello, Marcia Alberton ^{[1
]}

Lourega, Rogerio Vescia ^{[3
]}

Bizarro, Cristiano Valim ^{[1
,2
]}

Basso, Luiz Augusto ^{[1
,2
,4
]}

Machado, Pablo ^{[1
,2
,4
]}

机构：

[1] Pontificia Univ Catolica Rio Grande do Sul, Inst Nacl Ciencia & Tecnol TB, Ctr Pesquisas Biol Mol & Func, Ave Ipiranga,6681 Predio 92A, BR-90616900 Porto Alegre, RS, Brazil

[2] Pontificia Univ Catolica Rio Grande do Sul, Programa Posgrad Biol Celular & Mol, BR-90616900 Porto Alegre, RS, Brazil

[3] Univ Fed Rio Grande do Sul, Inst Quim, Dept Quim, BR-91501970 Porto Alegre, RS, Brazil

[4] Pontificia Univ Catolica Rio Grande do Sul, Programa Posgrad Med & Ciencias Saude, BR-90616900 Porto Alegre, RS, Brazil

来源：

MOLECULES | 2021年 / 26卷 / 17期

关键词：

1H-indoles; Mycobacterium tuberculosis; mammalian cellular viability; genotoxicity; time-kill; pharmacodynamic model; DRUG DISCOVERY; ARYLATION; CYCLIZATION; RESISTANCE; INDOLES; DESIGN; ASSAY;

D O I：

10.3390/molecules26175148

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：14

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