1. Synthesis and Antimycobacterial Activity of 3-Phenyl-1 H -indoles.
- Author
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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, and Machado, Pablo
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MYCOBACTERIUM tuberculosis , *GENETIC toxicology , *TUBERCULOSIS , *WORLD health - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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