title: Tetradentate polyamines as efficient metallodrugs for Chagas disease treatment in murine model.
abstract: A series of tetraamine-based compounds was prepared, and their trypanocidal effects against Trypanosoma cruzi and cytotoxicity were determined through the determination of IC50values. In vivo assays were performed in mice, where parasitaemia levels were quantified by fresh blood examination and the assignment of a cure was determined by polymerase chain reaction and reactivation of blood parasitaemia levels after immunosuppression. The mechanisms of action were elucidated at metabolic and ultra-structural levels, by1H NMR, Fe-SOD inhibition and TEM studies. The high-selectivity indexes observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. Compound 6 induced a remarkable decrease in the reactivation of parasitaemia after immunosuppression and curative rates of 33%. The experiments allowed us to select compound 6 as a promising candidate for treating Chagas disease, but a further high-level study should be considered to obtain an improved efficiency.
authors.affiliation: a Departamento de Parasitología , Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios De Granada/Universidad de Granada , Granada , Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Olmo
authors.affiliation: b QBIS Research Group, Departament de Química, Institut de Quimica Computacional i Catàlisi (IQCC) , Universitat de Girona , Campus de Montilivi, E-17071, Girona , Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Costas
authors.affiliation: a Departamento de Parasitología , Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios De Granada/Universidad de Granada , Granada , Spain.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Marín
authors.affiliation: a Departamento de Parasitología , Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios De Granada/Universidad de Granada , Granada , Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Rosales
authors.affiliation: a Departamento de Parasitología , Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios De Granada/Universidad de Granada , Granada , Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Martín-Escolano
authors.affiliation: b QBIS Research Group, Departament de Química, Institut de Quimica Computacional i Catàlisi (IQCC) , Universitat de Girona , Campus de Montilivi, E-17071, Girona , Spain.
authors.forename: Olaf
authors.initials: O
authors.lastname: Cussó
authors.affiliation: c Department of Statistics , University of Granada , Severo Ochoa s/n, E-18071 Granada , Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Gutierrez-Sánchez
authors.affiliation: b QBIS Research Group, Departament de Química, Institut de Quimica Computacional i Catàlisi (IQCC) , Universitat de Girona , Campus de Montilivi, E-17071, Girona , Spain.
authors.forename: Xavi
authors.initials: X
authors.lastname: Ribas
authors.affiliation: a Departamento de Parasitología , Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios De Granada/Universidad de Granada , Granada , Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Moreno
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D009942:Organometallic Compounds; D011073:Polyamines; C052141:dichlorotetramine palladium(II)
keywords: American trypanosomiasis; Chemotherapy; Murine model; Tetradentate polyamines