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Antiparasitic activity of aromatic diamidines is related to apoptosis-like death in Trypanosoma cruzi

Published online by Cambridge University Press:  27 March 2006

E. M. DE SOUZA ,
R. MENNA-BARRETO ,
T. C. ARAÚJO-JORGE ,
A. KUMAR ,
Q. HU ,
D. W. BOYKIN  and
M. N. C. SOEIRO
E. M. DE SOUZA
Affiliation:
Lab. Biologia Celular, DUBC, Instituto Oswaldo Cruz, FIOCRUZ, Avenida Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brasil
R. MENNA-BARRETO
Affiliation:
Lab. Biologia Celular, DUBC, Instituto Oswaldo Cruz, FIOCRUZ, Avenida Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brasil
T. C. ARAÚJO-JORGE
Affiliation:
Lab. Biologia Celular, DUBC, Instituto Oswaldo Cruz, FIOCRUZ, Avenida Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brasil
A. KUMAR
Affiliation:
Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA
Q. HU
Affiliation:
Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA
D. W. BOYKIN
Affiliation:
Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA
M. N. C. SOEIRO
Affiliation:
Lab. Biologia Celular, DUBC, Instituto Oswaldo Cruz, FIOCRUZ, Avenida Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brasil
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Abstract

Two aromatic diamidines, furamidine (DB75) and its phenyl-substituted analogue (DB569), which exhibit trypanocidal activity, were assayed against Trypanosoma cruzi and were found to induce apoptosis-like death characteristics such as nuclear DNA condensation and fragmentation, decreased mitochondrial membrane potential and phosphatidylserine exposure. DB569 displays superior trypanocidal activity compared to furamidine and also had higher ability to induce apoptosis-like death in treated parasites. The present results showing apoptosis-like death in T. cruzi after treatment with both DB75 and DB569 make important contributions to the understanding of the mechanisms of the aromatic diamidines, which represent promising trypanocidal compounds.

Keywords

aromatic diamidinesTrypanosoma cruziapoptosis-like deathtrypanocidal compounds
Type
Research Article
Information
Parasitology , Volume 133 , Issue 1 , July 2006 , pp. 75 - 79
Copyright
2006 Cambridge University Press

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