Article
Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative
Registro en:
CUPELLO, Mauricio Peixoto; et al. Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative. BioMed Research International, Volume 2017, Article ID 2483652, 8p, 2017.
2314-6133
10.1155/2017/2483652
2314-6141
Autor
Cupello, Mauricio Peixoto
Saraiva, Francis Monique
Ippolito, Pedro
Fernandes, Andréia da Silva
Menna-Barreto, Rubem Figueiredo Sadok
Costa, Debora de Sousa dos Santos
Paula, Jessica Isis Oliveira
Costa, Paulo Roberto Ribeiro
Nogueira, Natália Pereira
Felzenswalb, Israel
Dias, Ayres Guimarães
Paes, Marcia Cristina
Resumen
The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. Therefore, new therapeutical options are mandatory. In the present work, we evaluated the effect of a phenyl-tert-butylnitrone (PBN) derivate, LQB 123, againstTrypanosoma cruziforms. LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC50= 259.4 ± 6.1 μM) and intracellular amastigotes infecting peritoneal macrophages (IC50= 188.2 ± 47.5 μM), with no harmful effects upon the mammalian cells (CC50values greater than 4 mM), resulting in a high selectivity index (CC50/IC50> 20). Additionally, metacyclic trypomastigotes submitted to LQB 123 presented an IC50of about 191.8 ± 10.5 μM and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC50of 255.1 ± 3.6 μM. Finally, we investigated the mutagenic potential of the nitrone by theSalmonella/microsome assay and observed no induction of mutagenicity even in concentrations as high as 33000 μM. Taken together, these results present a nonmutagenic compound, with trypanocidal activity against all relevant forms ofT. cruzi, offering new insights into CD treatment suggesting additional in vivo tests.