title: Trypanosoma cruzi: activity of heterocyclic cationic molecules in vitro.
abstract: Chagas disease remains a serious public health problem in several Latin American countries. New chemotherapy is urgently needed since current drugs are limited in efficacy and exhibit undesirable side effects. Aromatic diamidines and analogs are well known anti-parasitic agents and in this study, we have evaluated the in vitro trypanocidal effect of several different heterocyclic cationic compounds, including diamidines (DB1195, DB1196 and DB1345), a monoamidine (DB824), an arylimidamide (DB613A) and a guanylhydrazone (DB1080) against amastigotes and bloodstream trypomastigotes of Trypanosoma cruzi, the etiological agent of Chagas disease. Our present findings showed that all compounds exerted, at low-micromolar doses, a trypanocidal effect upon both intracellular parasites and bloodstream trypomastigotes of T. cruzi. The activity of DB1195, DB1345, DB824 and DB1080 against bloodstream forms was reduced when these compounds were assayed in the presence of mouse blood possibly due to their association with plasma constituents and/or due to metabolic instability of the compounds. However, trypanocidal effects of DB613A and DB1196 were not affected by plasma constituents, suggesting their potential application in the prophylaxis of banked blood. In addition, potency and selectivity of DB613A, towards intracellular parasites, corroborate previous results that demonstrated the highly promising activity of arylimidamides against this parasite, which justify further studies in experimental models of T. cruzi infection.
authors.affiliation: Lab. Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, M.N.C. Soeiro, Rio de Janeiro, Brazil.
authors.forename: Michele Gabriele de Oliveira
authors.initials: MG
authors.lastname: Pacheco
authors.forename: Cristiane França
authors.initials: CF
authors.lastname: da Silva
authors.forename: Elen Mello
authors.initials: EM
authors.lastname: de Souza
authors.forename: Marcos Meuser
authors.initials: MM
authors.lastname: Batista
authors.forename: Patrícia Bernardino
authors.initials: PB
authors.lastname: da Silva
authors.forename: Arvind
authors.initials: A
authors.lastname: Kumar
authors.forename: Chad E
authors.initials: CE
authors.lastname: Stephens
authors.forename: David W
authors.initials: DW
authors.lastname: Boykin
authors.forename: Maria de Nazaré C
authors.initials: Mde N
authors.lastname: Soeiro
mesh_terms: D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D021261:Parasitic Sensitivity Tests; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D000578:Amidines; D006571:Heterocyclic Compounds; D014344:Trypanocidal Agents