TY - JOUR
T1 - Trypanosoma cruzi
T2 - Activity of heterocyclic cationic molecules in vitro
AU - Pacheco, Michele Gabriele de Oliveira
AU - Silva, Cristiane França da
AU - Souza, Elen Mello de
AU - Batista, Marcos Meuser
AU - Silva, Patrícia Bernardino da
AU - Kumar, Arvind
AU - Stephens, Chad E.
AU - Boykin, David W.
AU - Soeiro, Maria de Nazaré C.
N1 - Funding Information:
This study was supported by grants from Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (APQ1 and Pensa Rio), Conselho Nacional Desenvolvimento científico e Tecnológico (CNPq), DECIT/SCTIE/MS and MCT by CNPq, PAPES V/FIOCRUZ. Funding to DWB by the Bill and Melinda Gates Foundation is gratefully acknowledged.
PY - 2009/9
Y1 - 2009/9
N2 - 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.
AB - 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.
KW - Chagas disease
KW - Diamidines
KW - Trypanosoma cruzi
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U2 - 10.1016/j.exppara.2009.06.004
DO - 10.1016/j.exppara.2009.06.004
M3 - Article
C2 - 19520077
AN - SCOPUS:68049148349
SN - 0014-4894
VL - 123
SP - 73
EP - 80
JO - Experimental Parasitology
JF - Experimental Parasitology
IS - 1
ER -
