Novel Imidazo[4,5-c][1,2,6]thiadiazine 2,2-dioxides as antiproliferative trypanosoma cruzi drugs: Computational screening from neural network, synthesis and in vivo biological properties.
Eur J Med Chem
; 136: 223-234, 2017 Aug 18.
Article
em En
| MEDLINE
| ID: mdl-28499168
ABSTRACT
A new family of imidazo[4,5-c][1,2,6]thiadiazine 2,2-dioxide with antiproliferative Trypanosoma cruzi properties was identified from a neural network model published by our group. The synthesis and evaluation of this new class of trypanocidal agents are described. These compounds inhibit the growth of Trypanosoma cruzi, comparable with benznidazole or nifurtimox. In vitro assays were performed to study their effects on the growth of the epimastigote form of the Tulahuen 2 strain, as well as the epimastigote and amastigote forms of CL clone B5 of Trypanosoma cruzi. To verify selectivity towards parasite cells, the non-specific cytotoxicity of the most relevant compounds was studied in mammalian cells, i.e. J774 murine macrophages and NCTC clone 929 fibroblasts. Furthermore, these compounds were assayed regarding the inhibition of cruzipain. In vivo studies revealed that one of the compounds, 19, showed interesting trypanocidal activity, and could be a very promising candidate for the treatment of Chagas disease.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiadiazinas
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Trypanosoma cruzi
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Redes Neurais de Computação
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Imidazóis
Tipo de estudo:
Diagnostic_studies
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Screening_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article