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In vitro and in vivo activity of the chloroaryl-substituted imidazole viniconazole against Trypanosoma cruzi

Published online by Cambridge University Press:  22 October 2013

CRISTIANE FRANÇA DA SILVA ,
DENISE DA GAMA JAEN BATISTA ,
MARCOS MEUSER BATISTA ,
JESSICA LIONEL ,
ERICA RIPOLL HAMMER ,
RETO BRUN  and
MARIA DE NAZARÉ CORREIA SOEIRO
CRISTIANE FRANÇA DA SILVA
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
DENISE DA GAMA JAEN BATISTA
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
MARCOS MEUSER BATISTA
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
JESSICA LIONEL
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
ERICA RIPOLL HAMMER
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
RETO BRUN
Affiliation:
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
MARIA DE NAZARÉ CORREIA SOEIRO*
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
*
* Corresponding author: Laboratory of Cellular Biology, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365 Manguinhos, Rio de Janeiro, Brazil. E-mail: soeiro@ioc.fiocruz.br
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Summary

Chagas disease (CD) is caused by the intracellular protozoan parasite Trypanosoma cruzi and affects more than 10 million people in poor areas of Latin America. There is an urgent need for alternative drugs with better safety, broader efficacy, lower costs and shorter time of administration. Thus the biological activity of viniconazole, a chloroaryl-substituted imidazole was investigated using in vitro and in vivo screening models of T. cruzi infection. Ultrastructural findings demonstrated that the most frequent cellular damage was associated with plasma membrane (blebs and shedding events), Golgi (swelling aspects) and the appearance of large numbers of vacuoles suggesting an autophagic process. Our data demonstrated that although this compound is effective against bloodstream and intracellular forms (16 and 24 μ m, respectively) in vitro, it does not present in vivo efficacy. Due to the urgent need for novel agents against T. cruzi, the screening of natural and synthetic products must be further supported with the aim of finding more selective and affordable drugs for CD.

Keywords

Chagas diseaseTrypanosoma cruzichloroaryl-substituted imidazoleviniconazoleexperimental chemotherapyin vivoin vitro
Type
Research Article
Information
Parasitology , Volume 141 , Issue 3 , March 2014 , pp. 367 - 373
Copyright
Copyright © Cambridge University Press 2013 

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References

REFERENCES

Barrera, P. A., Jimenez-Ortiz, V., Tonn, C., Giordano, O., Galanti, N. and Sosa, M. A. (2008). Natural sesquiterpene lactones are active against Leishmania mexicana . Journal of Parasitology 94, 1143–1149. doi: 10.1645/GE-1501.1.CrossRefGoogle ScholarPubMed
Batista, D. da G., Batista, M. M., de Oliveira, G. M., do Amaral, P. B., Lannes-Vieira, J., Britto, C. C., Junqueira, A., Lima, M. M., Romanha, A. J., Sales, P. A. Junior, Stephens, C. E., Boykin, D. W. and Soeiro, M. de N. (2010). Arylimidamide DB766, a potential chemotherapeutic candidate for Chagas' disease treatment. Antimicrobial Agents Chemotherapy 54, 2940–2952. doi: 10.1128/AAC.01617-09.CrossRefGoogle ScholarPubMed
Batista, D. da G., Batista, M. M., de Oliveira, G. M., Britto, C. C., Rodrigues, A. C., Stephens, C. E., Boykin, D. W. and Soeiro, M. de N. (2011). Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo . PLoS ONE 6, e22155. doi: 10.1371/journal.pone.0022155.CrossRefGoogle ScholarPubMed
Brener, Z. (1962). Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi . Revista do Instituto de Medicina Tropical de Sao Paulo 4, 389–396.Google ScholarPubMed
da Silva, C. F., Batista, D. da G., Oliveira, G. M., de Souza, E. M., Hammer, E. R., da Silva, P. B., Daliry, A., Araujo, J. S., Britto, C., Rodrigues, A. C., Liu, Z., Farahat, A. A., Kumar, A., Boykin, D. W. and Soeiro, M. de N. (2012). In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form – DB1965 – against Trypanosoma cruzi infection. PLoS ONE 7, e30356.CrossRefGoogle ScholarPubMed
da Silva, C. F., Batista, M. M., Batista, D. da G., de Souza, E. M., da Silva, P. B., de Oliveira, G. M., Meuser, A. S., Shareef, A. R., Boykin, D. W. and Soeiro, M. de N. (2008). In vitro and in vivo studies of the trypanocidal activity of a diarylthiophene diamidine against Trypanosoma cruzi . Antimicrobial Agents Chemotherapy 52, 3307–3314.CrossRefGoogle ScholarPubMed
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. (2004). Phenyl substitution of furamidine markedly potentiates its anti-parasitic activity against Trypanosoma cruzi and Leishmania amazonensis . Biochemical Pharmacology 68, 593–600.CrossRefGoogle ScholarPubMed
Hargrove, T. Y., Kim, K., de Nazaré Correia Soeiro, M., da Silva, C. F., Batista, D. D., Batista, M. M., Yazlovitskaya, E. M., Waterman, M. R., Sulikowski, G. A. and Lepesheva, G. I. (2012). CYP51 structures and structure-based development of novel, pathogen-specific inhibitory scaffolds. International Journal for Parasitology: Drugs and Drug Resistance 2, 178–186.Google ScholarPubMed
Martins-Melo, F. R., Ramos, A. N. Jr., Alencar, C. H. and Heukelbach, J. (2012). Mortality due to Chagas disease in Brazil from 1979 to 2009: trends and regional differences. Journal of Infection in Developing Countries 26, 817–824. doi: 10.3855/jidc.2459.CrossRefGoogle Scholar
Meirelles, M. N., Araujo-Jorge, T. C., Miranda, C. F., De Souza, W. and Barbosa, H. S. (1986). Interaction of Trypanosoma cruzi with heart muscle cells: ultrastructural and cytochemical analysis of endocytic vacuole formation and effect upon myogenesis in vitro . European Journal of Cell Biology 41, 198–206.Google ScholarPubMed
Nibret, E., Youns, M., Krauth-Siegel, R. L. and Wink, M. (2011). Biological activities of Xanthatin from Xanthium strumarium leaves. Phytotherapy Research 25, 1883–1890. doi: 10.1002/ptr.3651.CrossRefGoogle ScholarPubMed
Nour, A. M., Khalid, S. A., Kaiser, M., Brun, R., Abdallah, W. E. and Schmidt, T. J. (2009). The antiprotozoal activity of sixteen asteraceae species native to Sudan and bioactivity-guided isolation of xanthanolides from Xanthium brasilicum . Planta Medica 75, 1363–1368. doi: 10.1055/s-0029-1185676.CrossRefGoogle ScholarPubMed
Schmidt, T. J., Khalid, S. A., Romanha, A. J., Alves, T. M., Biavatti, M. W., Brun, R., Da Costa, F. B., de Castro, S. L., Ferreira, V. F., de Lacerda, M. V., Lago, J. H., Leon, L. L., Lopes, N. P., das Neves Amorim, R. C., Niehues, M., Ogungbe, I. V., Pohlit, A. M., Scotti, M. T., Setzer, W. N., Soeiro, M. de N. C., Steindel, M. and Tempone, A. G. (2012 a). The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases – Part I. Current Medicinal Chemistry 19, 2128–2175.CrossRefGoogle ScholarPubMed
Schmidt, T. J., Khalid, S. A., Romanha, A. J., Alves, T. M., Biavatti, M. W., Brun, R., Da Costa, F. B., de Castro, S. L., Ferreira, V. F., de Lacerda, M. V., Lago, J. H., Leon, L. L., Lopes, N. P., das Neves Amorim, R. C., Niehues, M., Ogungbe, I. V., Pohlit, A. M., Scotti, M. T., Setzer, W. N., Soeiro, M. de N. C., Steindel, M. and Tempone, A. G. (2012 b). The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases – Part II. Current Medicinal Chemistry 19, 2176–2228.CrossRefGoogle ScholarPubMed
Soeiro, M. N. C., Daliry, A., Silva, C. F., de Souza, E. M., Oliveira, G. G., Salomão, K., Menna Barreto, R. and Castro, S. L. (2010). Electron microscopy approaches for the investigation of the cellular targets of trypanocidal agents in Trypanosoma cruzi . In Microscopy: Science, Technology, Applications and Education (Org. Méndez-Vilas, A., and Díaz, J.), Vol. 1, pp. 191–203. Badajoz, Formatex Research Center.Google Scholar
Soeiro, M. N., Werbovetz, K., Boykin, D. W., Wilson, W. D., Wang, M. Z. and Hemphill, A. (2013a). Novel amidines and analogues as promising agents against intracellular parasites: a systematic review. Parasitology 140, 929–951. doi: 10.1017/S0031182013000292.CrossRefGoogle ScholarPubMed
Soeiro, M. D., de Souza, E. M., da Silva, C. F., da Gama Jaen Batista, D., Batista, M. M., Pavão, B. P., Araújo, J. S., Aiub, C. A., da Silva, P. B., Lionel, J., Britto, C., Kim, K., Sulikowski, G., Hargrove, T. Y., Waterman, M. R. and Lepesheva, G. I. (2013 b). Antiparasitic activity of sterol 14α-demethylase (CYP51) inhibitor VNI against drug-resistant strains of Trypanosoma cruzi: in vitro and in vivo studies. Antimicrobial Agents and Chemotherapy 57, 4151–4163.CrossRefGoogle ScholarPubMed
Urbina, J. A. (2009). New advances in the management of a long-neglected disease. Clinical Infectious Disease 49, 1685–1687. doi: 10.1086/648073.CrossRefGoogle ScholarPubMed
Villalta, F., Dobish, M. C., Nde, P. N., Kleshchenko, Y. Y., Hargrove, T. Y., Johnson, C. A., Waterman, M. R., Johnston, J. N. and Lepesheva, G. I. (2013). VNI cures acute and chronic experimental Chagas disease. Journal of Infectious Diseases 208, 504–511.CrossRefGoogle ScholarPubMed