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Journal of Bioenergetics and Biomembranes

, Volume 50, Issue 2, pp 81–91 | Cite as

Searching for new drugs for Chagas diseases: triazole analogs display high in vitro activity against Trypanosoma cruzi and low toxicity toward mammalian cells

  • Robson Xavier Faria
  • Daniel Tadeu Gomes Gonzaga
  • Paulo Anastácio Furtado Pacheco
  • André Luis Almeida Souza
  • Vitor Francisco Ferreira
  • Fernando de Carvalho da Silva
Article
  • 211 Downloads

Abstract

Chagas disease is one of the most relevant endemic diseases in Latin America caused by the flagellate protozoan Trypanosoma cruzi. Nifurtimox and benzonidazole are the drugs used in the treatment of this disease, but they commonly are toxic and present severe side effects. New effective molecules, without collateral effects, has promoted the investigation to develop new lead compounds with to advance for clinical trials. Previously, 3-nitro-1H-1,2,4-triazole-based amines and 1,2,3-triazoles demonstrated significant trypanocidal activity against T. cruzi. In this paper, we synthesized a new series of 92 examples of 1,2,3-triazoles. Six compounds exhibited antiparasitic activity, 14, 25, 27, 31 and 40, 43 and were effective against epimastigotes of two strains of T. cruzi (Y and Dm28-C) and 25, 27 and 31 exhibited trypanocidal activity similar to benzonidazole. Notably, the compound 25 compared to benzonidazole increase the toxicity against T. cruzi, with no apparent toxicity to the cell line of mice macrophages or primary mice peritoneal macrophages. As results, we calculated selectivity indexes up to 2000 to 25 and 31 in both T. cruzi strains. Derivative 14 caused a trypanostatic effect because it did not damage external epimastigote membrane. Triazoles 40 and 43 impaired parasites viability using a pathway not dependent on ROS production.

Keywords

1,2,3-triazoles Epimastigotes strains Y strain Dm28-C strain 

Notes

Acknowledgments

We acknowledge Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Auxílio à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and, Programa Institucional de Indução a Ciência, Tecnologia e Inovação em Saúde (PAPES VI) for their financial support.

Author contributions

Robson Xavier Faria and André Luis Souza designed the research; Fernando de Carvalho da Silva, Vitor Francisco Ferreira e Robson Xavier Faria provided the space and the reagents; Robson Xavier Faria and André Luis Souza performed the experiments; Daniel Tadeu Gomes Gonzaga synthetized the triazoles, Fernando de Carvalho da Silva and Robson Xavier Faria wrote the manuscript. All authors have read and approved the final version of the manuscript.

Compliance with ethical standards

Conflicts of interests

The author(s) declare that they have no competing interests.

Supplementary material

10863_2018_9746_MOESM1_ESM.docx (23 kb)
Supplemental Figure S1 (DOCX 23 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Robson Xavier Faria
    • 1
  • Daniel Tadeu Gomes Gonzaga
    • 2
  • Paulo Anastácio Furtado Pacheco
    • 2
  • André Luis Almeida Souza
    • 3
  • Vitor Francisco Ferreira
    • 4
  • Fernando de Carvalho da Silva
    • 2
  1. 1.Laboratory of Toxoplasmosis and other ProtozoansOswaldo Cruz Institute - FiocruzRio de JaneiroBrazil
  2. 2.Departamento de Química Orgânica, Instituto de QuímicaUniversidade Federal FluminenseNiteróiBrazil
  3. 3.Laboratory of Biochemistry of PeptidesOswaldo Cruz Institute – FiocruzRio de JaneiroBrazil
  4. 4.Departamento de Tecnologia Farmacêutica, Faculdade de FarmáciaUniversidade Federal FluminenseNiteróiBrazil

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