We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Searching for new drugs for Chagas diseases: triazole analogs display high in vitro activity against <italic>Trypanosoma cruzi</italic> 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; da Silva, Fernando de Carvalho
- Abstract
Chagas disease is one of the most relevant endemic diseases in Latin America caused by the flagellate protozoan <italic>Trypanosoma cruzi</italic>. 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-1<italic>H</italic>-1,2,4-triazole-based amines and 1,2,3-triazoles demonstrated significant trypanocidal activity against <italic>T. cruzi</italic>. In this paper, we synthesized a new series of 92 examples of 1,2,3-triazoles. Six compounds exhibited antiparasitic activity, <bold>14</bold>, <bold>25</bold>, <bold>27</bold>, <bold>31</bold> and <bold>40</bold>, <bold>43</bold> and were effective against epimastigotes of two strains of <italic>T. cruzi</italic> (Y and Dm28-C) and <bold>25</bold>, <bold>27</bold> and <bold>31</bold> exhibited trypanocidal activity similar to benzonidazole. Notably, the compound <bold>25</bold> compared to benzonidazole increase the toxicity against <italic>T. cruzi</italic>, 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 <bold>25</bold> and <bold>31</bold> in both <italic>T. cruzi</italic> strains. Derivative <bold>14</bold> caused a trypanostatic effect because it did not damage external epimastigote membrane. Triazoles <bold>40</bold> and <bold>43</bold> impaired parasites viability using a pathway not dependent on ROS production.
- Subjects
LATIN America; CHAGAS' disease treatment; TRIAZOLES; TRYPANOSOMA cruzi; PUBLIC health; DRUG side effects; THERAPEUTICS
- Publication
Journal of Bioenergetics & Biomembranes, 2018, Vol 50, Issue 2, p81
- ISSN
0145-479X
- Publication type
Article
- DOI
10.1007/s10863-018-9746-z