Biological activity of 1,2,3,4-tetrahydro-beta-carboline-3-carboxamides against Trypanosoma cruzi.
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.
Valdez
Rodrigo Hinojosa
RH
Programa de Pós-graduação em Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, Campus Universitário, Londrina, Paraná, Brazil.
Tonin
Lilian Tatiani Düsman
LT
Ueda-Nakamura
Tânia
T
Dias Filho
Benedito Prado
BP
Morgado-Diaz
José Andrés
JA
Sarragiotto
Maria Helena
MH
Nakamura
Celso Vataru
CV
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
D000962:Antimalarials; D002243:Carbolines