2. Academic Validation
  3. Synthesis and Antimycobacterial Activity of 3-Phenyl-1 H-indoles

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

  • Molecules. 2021 Aug 25;26(17):5148. doi: 10.3390/molecules26175148.
Renata Jardim Etchart 1 2,  Raoní S Rambo 1,  Bruno Lopes Abbadi 1,  Nathalia Sperotto 1,  Christiano Ev Neves 1 2,  Fernanda Fries Silva 1 2,  Maiele Dornelles 1,  Lovaine Duarte 1,  Fernanda Souza Macchi 1 2,  Marcia Alberton Perelló 1,  Rogério Vescia Lourega 3,  Cristiano Valim Bizarro 1 2,  Luiz Augusto Basso 1 2 4,  Pablo Machado 1 2 4
Affiliations

Affiliations

  • 1 Centro 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, Brazil.
  • 2 Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90616-900, RS, Brazil.
  • 3 Instituto de Química, Departamento de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, Brazil.
  • 4 Programa de Pós-Graduação em Medicina e Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90616-900, RS, Brazil.
PMID: 34500579 DOI: 10.3390/molecules26175148
Abstract

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.

Keywords

1H-indoles; Mycobacterium tuberculosis; genotoxicity; mammalian cellular viability; pharmacodynamic model; time-kill.

Figures
Products