Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/29531
Title: Searching for new drugs for Chagas diseases: triazole analogs display high in vitro activity against Trypanosoma cruzi and low toxicity toward mammalian cells
Authors: Faria, Robson Xavier
Gonzaga, Daniel Tadeu Gomes
Pacheco, Paulo Anastácio Furtado
Souza, André Luis Almeida
Ferreira, Vitor Francisco
Silva, Fernando de Carvalho da
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxoplasmose e outras Protozooses. Rio de Janeiro, RJ. Brasil.
Universidade Federal Fluminense. Campus do Valonguinho. Instituto de Química. Departamento de Química Orgânica. Niterói, RJ, Brasil.
Universidade Federal Fluminense. Campus do Valonguinho. Instituto de Química. Departamento de Química Orgânica. Niterói, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Peptídeos. Rio de Janeiro, RJ. Brasil.
Universidade Federal Fluminense. Faculdade de Farmácia. Departamento de Tecnologia Farmacêutica. Niterói, RJ, Brasil.
Universidade Federal Fluminense. Campus do Valonguinho. Instituto de Química. Departamento de Química Orgânica. Niterói, RJ, Brasil.
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
Chagas disease
keywords: Triazóis
Linhagens de epimastigotas
Doença de Chagas
Issue Date: 2018
Publisher: Springer Verlag (Germany)
Citation: FARIA, Robson Xavier; etal. Searching for new drugs for Chagas diseases: triazole analogs display high in vitro activity against Trypanosoma cruzi and low toxicity toward mammalian cells. Journal of Bioenergetics and Biomembranes, v.50, p.81–91, 2018.
DOI: 10.1007/s10863-018-9746-z
ISSN: 0145-479X
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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