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3100-12-31
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A STUDY OF THE ACTIVITY OF 2-(ALKYLAMINO)-1-PHENYL-1-ETHANETHIOSULFURIC ACIDS AGAINST INFECTION BY SCHISTOSOMA MANSONI IN A MURINE MODEL
Schistosoma mansoni
aminoalkanethiosulfuric acid
preclinical drug evaluation
drug resistance
toxicity
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Affilliation
Universidade Federal de Minas Gerais. Instituto de Ciências Exatas. Departamento de Química. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Exatas. Departamento de Química. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brazil
Fundação Osvaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/Santa Casa de Misericórdia de Belo Horizonte. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Alimentos. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Exatas. Departamento de Química. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brazil
Fundação Osvaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/Santa Casa de Misericórdia de Belo Horizonte. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Alimentos. Belo Horizonte, MG, Brazil
Abstract
The schistosomicidal. activities of seven 2-(alkytamino)-1-phenyl-1-ethanethiosulfuric acids (1a-g) (R = propyl, isopropyl, butyl, isobutyl, t-butyl, sec-butyl, cyclohexyl, respectively) were determined in female Swiss mice infected with Schistosoma mansoni. The compounds were administered in a single oral dose of 800 mg/kg to groups of 15 mice infected with 50 cercariae each. All the compounds were found to be active, a high animal mortality being observed with 1e. These compounds have a high specificity against female worms (64-100% reduction vs. 33-61% reduction in mate worms). The test was repeated, a 400-mg/kg sub-dose of 1f also being tested, and similar results were observed. A 94% reduction in the number of female worms was observed when compound 1c was administered in a single 800-mg/kg dose to animals infected with 80 cercariae. Finally, the test was repeated with single 800 mg/kg oral doses of compounds 1e (highly purified) and 1f and a 400-mg/kg sub-dose of 1c. The toxicity of le was confirmed, while the animals that received 1c and 1f presented reductions in the worm Loads corresponding to 45.9% (male worms) and 84.8% (female worms) for 1c and 50.4% (male worms) and 94.2% (female worms) for 1f.
Keywords
schistosomiasisSchistosoma mansoni
aminoalkanethiosulfuric acid
preclinical drug evaluation
drug resistance
toxicity
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