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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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References

REFERENCES

Ameisen, J. C., Idziorek, T., Billaut-Multo, A., Loyens, M., Yissier, J. P., Potentier, A. and Quaissi, A. ( 1995). Apoptosis in a unicellular eukaryote (Trypanosoma cruzi) – implications for the evolutionary origin and role of programmed cell death in the control of cell proliferation, differentiation and survival. Cell Death and Differentiation 2, 285–300.Google Scholar
Ameisen, J. C. ( 2002). On the origin, evolution, and nature of programmed cell death: a time line of four billion years. Cell Death and Differentiation 9, 367–393.CrossRefGoogle Scholar
Barcinski, M. A. and DosReis, G. A. ( 1999). Apoptosis in parasites and parasite-induced apoptosis in the host immune system: a new approach to parasitic diseases. Brazilian Journal of Medical Biology Research 32, 395–401.CrossRefGoogle Scholar
Barcinski, M. A., Moreira, M. E., Balanco, J. M., Wanderley, J. L. and Bonomo, A. C. ( 2003). The role of apoptotic mimicry in host-parasite interplay: is death the only alternative for altruistic behavior? Kinetoplastid Biology Disease 2, 6.Google Scholar
Chowdhury, A. R., Mandal, S., Goswami, A., Ghosh, M., Mandal, L., Chakraborty, D., Ganguly, A., Tripathi, G., Mukhopadhyay, S., Bandyopadhyay, S. and Majumder, H. K. ( 2003). Dihydrobetulinic acid induces apoptosis in Leishmania donovani by targeting DNA topoisomerase I and II: implications in antileishmanial therapy. Molecular Medicine 9, 26–36.Google Scholar
Coura, R. J. and de Castro, S. L. ( 2002). A critical review on Chagas' disease chemotherapy. Memórias do Instituto Oswaldo Cruz 97, 3–24.CrossRefGoogle Scholar
Croft, S. L. and Brazil, R. P. ( 1982). Effect of pentamidine isethionate on the ultrastructure and morphology of Leishmania mexicana amazonensis in vitro. Annals of Tropical Medicine and Parasitology 76, 37–43.CrossRefGoogle Scholar
De Souza, E. M., Lansiaux, A., Bailly, C., Wilson, W. D., Hu, Q., Boykin, D. W., Batista, M. M., Araújo-Jorge, T. C. and Soeiro, M. N. C. ( 2004). Phenyl substitution of furamidine markedly potentiates its antiparasitic activity against Trypanosoma cruzi and Leishmania amazonensis. Biochemical Pharmacology 68, 593–600.CrossRefGoogle Scholar
De Souza, E. M., Araujo-Jorge, T. C., Bailly, C., Lansiaux, A., Batista, M. M., Oliveira, G. M. and Soeiro, M. N. ( 2003). Host and parasite apoptosis following Trypanosoma cruzi infection in in vitro and in vivo models. Cell and Tissue Research 314, 223–235.CrossRefGoogle Scholar
Deolindo, P., Teixeira-Ferreira, A. S., Melo, E. J., Arnholdt, A. C., Souza, W., Alves, E. W. and DaMatta, R. A. ( 2005). Programmed cell death in Trypanosoma cruzi induced by Bothrops jararaca venom. Memórias do Instituto Oswaldo Cruz 100, 33–38.CrossRefGoogle Scholar
Lanteri, C. A., Trumpower, B. L., Tidwell, R. R. and Meshnick, S. R. ( 2004). DB75, a novel trypanocidal agent, disrupts mitochondrial function in Saccharomyces cerevisiae. Antimicrobial Agents and Chemotherapy 48, 3968–3974.CrossRefGoogle Scholar
Lee, N., Bertholet, S., Debrabant, A., Muller, J., Duncan, R. and Nakhasi, H. L. ( 2002). Programmed cell death in the unicellular protozoan parasite Leishmania. Cell Death and Differentiation 9, 53–64.CrossRefGoogle Scholar
Meirelles, M. N. L., Araújo-Jorge, T. C. and De Souza, W. ( 1982). Interaction of Trypanosoma cruzi with macrophages in vitro: dissociation of the attachment and internalization phases by low temperature and cytochalasin B. Zeitschrift für Parasitenkunde 68, 7–14.CrossRefGoogle Scholar
Mittra, B., Saha, A., Chowdhury, A. R., Pal, C., Mandal, S., Mukhopadhyay, S., Bandyopadhyay, S. and Majumder, H. K. ( 2000). Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis. Molecular Medicine 6, 527–541.Google Scholar
Nguewa, P. A., Fuertes, M. A., Valladares, B., Alonso, C. and Perez, J. M. ( 2004). Programmed cell death in trypanosomatids: a way to maximize their biological fitness? Trends Parasitology 20, 375–380.Google Scholar
Paris, C., Loiseau, P. M., Bories, C. and Breard, J. ( 2004). Miltefosine induces apoptosis-like death in Leishmania donovani promastigotes. Antimicrobial Agents and Chemotherapy 48, 852–859.CrossRefGoogle Scholar
Piacenza, L., Peluffo, G. and Radi, R. ( 2001). L-arginine-dependent suppression of apoptosis in Trypanosoma cruzi: contribution of the nitric oxide and polyamine pathways. Proceedings of the National Academy of Sciences, USA 98, 7301–7306.CrossRefGoogle Scholar
Soeiro, M. N. C., De Souza, E. M., Stephens, C. E. and Boykin, D. W. ( 2005). Aromatic diamidines as antiparasitic agents. Expert Opinion on Investigational Drugs 14, 957–972.CrossRefGoogle Scholar
Telford, W. G., Komoriya, A. and Packard, B. Z. ( 2004). Multiparametric analysis of apoptosis by flow and image cytometry. Methods in Molecular Biology 263, 141–160.CrossRefGoogle Scholar
Vercesi, A. E. and Docampo, R. ( 1992). Ca2+ transport by digitonin-permeabilized Leishmania donovani. Effects of Ca2+, pentamidine and WR-6026 on mitochondrial membrane potential in situ. The Biochemical Journal 284, 463–467.Google Scholar
WORLD HEALTH ORGANIZATION ( 2002). The world health report. World Health Organization, Geneva.
Wilson, W. D., Nguyen, B., Tanious, F. A., Mathis, A., Hall, J. E., Stephens, C. E. and Boykin, D. W. ( 2005). Dications that target the DNA minor groove: compound design and preparation, DNA interactions, cellular distribution and biological activity. Current Medicinal Chemistry 5, 380–408.CrossRefGoogle Scholar