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In Vitro and in Vivo Anti-Trypanosoma cruzi Activity of New Arylamine Mannich Base-Type Derivatives.

Authors :
Moreno-Viguri E
Jiménez-Montes C
Martín-Escolano R
Santivañez-Veliz M
Martin-Montes A
Azqueta A
Jimenez-Lopez M
Zamora Ledesma S
Cirauqui N
López de Ceráin A
Marín C
Sánchez-Moreno M
Pérez-Silanes S
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.

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