title: Biological activity of 1,2,3,4-tetrahydro-beta-carboline-3-carboxamides against Trypanosoma cruzi.
abstract: Several beta-carboline compounds were evaluated for in vitro trypanocidal activity against Trypanosoma cruzi and their potential toxic effects was also assessed. beta-Carboline derivative 4 showed good activity against epimastigote, trypomastigote, and amastigote forms of T. cruzi, with a dose-dependent inhibitory effect. It showed an IC(50) of 14.9 microM against the epimastigote form and an EC(50) of 45 microM and 33 microM against trypomastigote and amastigote forms, respectively. Additionally, 4 was able to be active on mammalian cell-protozoan interaction, reducing the number of infected cells and the number of internalized parasites. The compound showed low cytotoxicity, with a selective index 31 times higher to the parasite than for mammalian cells. In human red-blood cells beta-Carboline 4 at 14.9 microM not caused haemolysis. Observed at electron microscopy 4-treated epimastigotes showed abnormal swelling of the mitochondrion, a diffuse kinetoplast, and distortions of the parasite cell body. The present data support the potential effect of this class of compounds against T. cruzi and encourage further experiments in vitro to evaluate the action mechanism of this drug and also with in vivo models.
authors.affiliation: Programa de Pós-graduação em Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, Campus Universitário, Londrina, Paraná, Brazil.
authors.forename: Rodrigo Hinojosa
authors.initials: RH
authors.lastname: Valdez
authors.forename: Lilian Tatiani Düsman
authors.initials: LT
authors.lastname: Tonin
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.forename: Benedito Prado
authors.initials: BP
authors.lastname: Dias Filho
authors.forename: José Andrés
authors.initials: JA
authors.lastname: Morgado-Diaz
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Sarragiotto
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000633:toxicity; D002243:Carbolines / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D004912:Erythrocytes / Q000187:drug effects; D000882:Haplorhini; D006461:Hemolysis; D006801:Humans; D020128:Inhibitory Concentration 50; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D021261:Parasitic Sensitivity Tests; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D000962:Antimalarials; D002243:Carbolines