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In Vitro and in Vivo Anti-Trypanosoma cruzi Activity of New Arylamine Mannich Base-Type Derivatives.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2016 Dec 22; Vol. 59 (24), pp. 10929-10945. Date of Electronic Publication: 2016 Dec 06. - Publication Year :
- 2016
-
Abstract
- Chagas disease is a neglected tropical disease with 6-7 million people infected worldwide, and there is no effective treatment. Therefore, there is an urgent need to continue researching in order to discover novel therapeutic alternatives. We present a series of arylaminoketone derivatives as means of identifying new drugs to treat Chagas disease in the acute phase with greater activity, less toxicity, and a larger spectrum of action than that corresponding to the reference drug benznidazole. Indexes of high selectivity found in vitro formed the basis for later in vivo assays in BALB/c mice. Murine model results show that compounds 3, 4, 7, and 10 induced a remarkable decrease in parasitemia levels in acute phase and the parasitemia reactivation following immunosuppression, and curative rates were higher than with benznidazole. These high antiparasitic activities encourage us to propose these compounds as promising molecules for developing an easy to synthesize anti-Chagas agent.
- Subjects :
- Animals
Cells, Cultured
Chagas Disease parasitology
Chlorocebus aethiops
Disease Models, Animal
Dose-Response Relationship, Drug
Mannich Bases chemical synthesis
Mannich Bases chemistry
Mice
Mice, Inbred BALB C
Molecular Structure
Parasitic Sensitivity Tests
Structure-Activity Relationship
Trypanocidal Agents chemical synthesis
Trypanocidal Agents chemistry
Vero Cells
Chagas Disease drug therapy
Mannich Bases pharmacology
Trypanocidal Agents pharmacology
Trypanosoma cruzi drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 59
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 28002965
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.6b00784