Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative
| Autor: | Debora de Sousa dos Santos Costa, Francis M. S. Saraiva, Israel Felzenswalb, Rubem Figueiredo Sadoko Menna-Barreto, Andréia da Silva Fernandes, Mauricio Peixoto Cupello, Marcia Cristina Paes, Pedro Ippolito, Paulo R. R. Costa, Jéssica Isis Oliveira Paula, Natália Pereira de Almeida Nogueira, Ayres G. Dias |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chagas disease Article Subject Trypanosoma cruzi 030231 tropical medicine Drug Evaluation Preclinical lcsh:Medicine Drug resistance Pharmacology General Biochemistry Genetics and Molecular Biology Cyclic N-Oxides Inhibitory Concentration 50 Mice 03 medical and health sciences 0302 clinical medicine Salmonella medicine Animals Chagas Disease Amastigote Cytotoxicity IC50 General Immunology and Microbiology biology lcsh:R General Medicine medicine.disease biology.organism_classification Trypanocidal Agents 030104 developmental biology Mutagenesis Toxicity Macrophages Peritoneal Microsome Nitrogen Oxides Research Article Mutagens |
| Zdroj: | BioMed Research International, Vol 2017 (2017) BioMed Research International |
| ISSN: | 2314-6141 2314-6133 |
| Popis: | 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 about191.8±10.5 μM and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC50of255.1±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. |
| Databáze: | OpenAIRE |
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