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

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

  • J Med Chem. 2016 Dec 22;59(24):10929-10945. doi: 10.1021/acs.jmedchem.6b00784.
Elsa Moreno-Viguri 1,  Carmen Jiménez-Montes 2,  Rubén Martín-Escolano 2,  Mery Santivañez-Veliz 1,  Alvaro Martin-Montes 2,  Amaya Azqueta 3 4,  Marina Jimenez-Lopez 2,  Salvador Zamora Ledesma 2,  Nuria Cirauqui 5,  Adela López de Ceráin 3 4,  Clotilde Marín 2,  Manuel Sánchez-Moreno 2,  Silvia Pérez-Silanes 1
Affiliations

Affiliations

  • 1 Department of Organic and Pharmaceutical Chemistry, Institute of Tropical Health, Universidad de Navarra , Pamplona 31008, Spain.
  • 2 Departamento de Parasitología, Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios de Granada/Universidad de Granada , Granada 18014, Spain.
  • 3 Department of Pharmacology and Toxicology, Universidad de Navarra , Pamplona 31008, Spain.
  • 4 IdiSNA, Navarra Institute for Health Research, Recinto de Complejo Hospitalario de Navarra, Pamplona 31008, Spain.
  • 5 Department of Pharmaceutical Sciences, Federal University of Rio de Janeiro , Rio de Janeiro 21949-900, Brazil.
PMID: 28002965 DOI: 10.1021/acs.jmedchem.6b00784
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.

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