title: Nitrotriazole-Based Compounds as Antichagasic Agents in a Long-TreatmentIn VivoAssay.
abstract: 3-Nitrotriazole-based compounds belonging to various chemical subclasses were found to be very effective against Chagas disease bothin vitroandin vivoafter a short administration schedule. In this study, five compounds with specific characteristics were selected to be administered for longer periods of time to mice infected with the virulentTrypanosoma cruziY strain to further evaluate their effectiveness as antichagasic agents and whether or not potential adverse effects occur. Benznidazole was included for comparison purposes. Complete parasitemia depletion, weight gain, 100% survival, and a lack of myocardial inflammation were observed with four of the compounds and benznidazole administered intraperitoneally at 15 or 20 mg/kg of body weight/day for 40 days. There was a significant reduction in the number of treatment days (number of doses) necessary to induce parasitemia suppression with all four compounds compared to that required with benznidazole. Partial cures were obtained with only one compound tested at 15 mg/kg/day and on the schedule mentioned above but not with benznidazole. Taken together, our data suggest that these compounds demonstrate potent trypanocidal activity comparable to or better than that of the reference drug, benznidazole, when they are administered at the same dose and on the same schedule.
authors.affiliation: NorthShore University HealthSystem, Department of Radiation Medicine, Evanston, Illinois, USA mvpapadopoulou@gmail.com mtbahia@pq.cnpq.br.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Papadopoulou
authors.affiliation: NorthShore University HealthSystem, Department of Radiation Medicine, Evanston, Illinois, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Bloomer
authors.affiliation: Oakton Community College, Des Plaines, Illinois, USA.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Rosenzweig
authors.affiliation: Universidade Federal de Ouro Preto, Ouro Petro, Minas Gerais, Brazil.
authors.forename: Ana Lia
authors.initials: AL
authors.lastname: Mazzeti
authors.affiliation: Universidade Federal de Ouro Preto, Ouro Petro, Minas Gerais, Brazil.
authors.forename: Karolina Ribeiro
authors.initials: KR
authors.lastname: Gonçalves
authors.affiliation: Universidade Federal de Ouro Preto, Ouro Petro, Minas Gerais, Brazil.
authors.forename: Priscila Fagundes
authors.initials: PF
authors.lastname: Mendes
authors.affiliation: Universidade Federal de Ouro Preto, Ouro Petro, Minas Gerais, Brazil mvpapadopoulou@gmail.com mtbahia@pq.cnpq.br.
authors.forename: Maria Terezinha
authors.initials: MT
authors.lastname: Bahia
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D009593:Nitroimidazoles / Q000494:pharmacology*; D018512:Parasitemia / Q000188:drug therapy*; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D009593:Nitroimidazoles; D014230:Triazoles; D014344:Trypanocidal Agents; C009999:benzonidazole
keywords: Chagas disease; benznidazole; long treatment; nitrotriazoles