title: In Vitro and in Vivo Anti-Trypanosoma cruzi Activity of New Arylamine Mannich Base-Type Derivatives.
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.
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Institute of Tropical Health, Universidad de Navarra , Pamplona 31008, Spain.
authors.forename: Elsa
authors.identifier: 0000-0001-6302-6230
authors.initials: E
authors.lastname: Moreno-Viguri
authors.affiliation: Departamento de Parasitología, Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios de Granada/Universidad de Granada , Granada 18014, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Jiménez-Montes
authors.affiliation: Departamento de Parasitología, Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios de Granada/Universidad de Granada , Granada 18014, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Martín-Escolano
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Institute of Tropical Health, Universidad de Navarra , Pamplona 31008, Spain.
authors.forename: Mery
authors.initials: M
authors.lastname: Santivañez-Veliz
authors.affiliation: Departamento de Parasitología, Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios de Granada/Universidad de Granada , Granada 18014, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Martin-Montes
authors.affiliation: Department of Pharmacology and Toxicology, Universidad de Navarra , Pamplona 31008, Spain.|IdiSNA, Navarra Institute for Health Research, Recinto de Complejo Hospitalario de Navarra, Pamplona 31008, Spain.
authors.forename: Amaya
authors.initials: A
authors.lastname: Azqueta
authors.affiliation: Departamento de Parasitología, Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios de Granada/Universidad de Granada , Granada 18014, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Jimenez-Lopez
authors.affiliation: Departamento de Parasitología, Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios de Granada/Universidad de Granada , Granada 18014, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Zamora Ledesma
authors.affiliation: Department of Pharmaceutical Sciences, Federal University of Rio de Janeiro , Rio de Janeiro 21949-900, Brazil.
authors.forename: Nuria
authors.initials: N
authors.lastname: Cirauqui
authors.affiliation: Department of Pharmacology and Toxicology, Universidad de Navarra , Pamplona 31008, Spain.|IdiSNA, Navarra Institute for Health Research, Recinto de Complejo Hospitalario de Navarra, Pamplona 31008, Spain.
authors.forename: Adela
authors.initials: A
authors.lastname: López de Ceráin
authors.affiliation: Departamento de Parasitología, Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios de Granada/Universidad de Granada , Granada 18014, Spain.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Marín
authors.affiliation: Departamento de Parasitología, Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios de Granada/Universidad de Granada , Granada 18014, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Moreno
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Institute of Tropical Health, Universidad de Navarra , Pamplona 31008, Spain.
authors.forename: Silvia
authors.identifier: 0000-0002-6284-4546
authors.initials: S
authors.lastname: Pérez-Silanes
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008352:Mannich Bases / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D008352:Mannich Bases; D014344:Trypanocidal Agents