Design, Synthesis, Trypanocidal Activity, and Studies on Human Album in Interaction of Novel S-Alkyl-1,2,4-triazoles
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Journal of the Brazilian Chemical Society (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000701378 |
Resumo: | Chagas disease is a neglected tropical disease caused by the hemoflagellated parasite Trypanosoma cruzi (Kinetoplastida). The only available drug to treat chagasic patients in Brazil, the nitroheterocycle benznidazole, is effective solely during the acute phase of the infection. There is accordingly a need to develop new therapeutic tools for the treatment of Chagas disease. This work reports the synthesis, trypanocidal evaluation and human serum albumin (HSA) interactions of a novel series of 1,2,4-triazoles. The new derivatives were synthesized via microwave irradiation in good yields. Most compounds showed toxic effects against T. cruzi with low toxicity to host cells. Three S-alkylated-triazoles showed the best activity profile against amastigotes, with half maximal inhibitory concentration (IC50) values of 3.95 ± 1.41, 4.15 ± 0.92 and 3.61 ± 0.65 µmol L-1, respectively. The interaction between HSA and 3-[(1E,3E)-4-(1,3-benzodioxol-5-yl)buta-1,3-dien-1-yl]-5-(butylthio)-4-cyclohexyl-4,5-dihydro-1H-1,2,4-triazole was investigated using multiple spectroscopic techniques and molecular docking, revealing that serum albumin is a potential endogenous carrier to this compound in the human bloodstream. |
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Design, Synthesis, Trypanocidal Activity, and Studies on Human Album in Interaction of Novel S-Alkyl-1,2,4-triazolesTrypanosoma cruzipiperinemolecular hybridization1,2,4-triazole-3-thioetherhuman serum albuminChagas disease is a neglected tropical disease caused by the hemoflagellated parasite Trypanosoma cruzi (Kinetoplastida). The only available drug to treat chagasic patients in Brazil, the nitroheterocycle benznidazole, is effective solely during the acute phase of the infection. There is accordingly a need to develop new therapeutic tools for the treatment of Chagas disease. This work reports the synthesis, trypanocidal evaluation and human serum albumin (HSA) interactions of a novel series of 1,2,4-triazoles. The new derivatives were synthesized via microwave irradiation in good yields. Most compounds showed toxic effects against T. cruzi with low toxicity to host cells. Three S-alkylated-triazoles showed the best activity profile against amastigotes, with half maximal inhibitory concentration (IC50) values of 3.95 ± 1.41, 4.15 ± 0.92 and 3.61 ± 0.65 µmol L-1, respectively. The interaction between HSA and 3-[(1E,3E)-4-(1,3-benzodioxol-5-yl)buta-1,3-dien-1-yl]-5-(butylthio)-4-cyclohexyl-4,5-dihydro-1H-1,2,4-triazole was investigated using multiple spectroscopic techniques and molecular docking, revealing that serum albumin is a potential endogenous carrier to this compound in the human bloodstream.Sociedade Brasileira de Química2019-07-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000701378Journal of the Brazilian Chemical Society v.30 n.7 2019reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.21577/0103-5053.20190033info:eu-repo/semantics/openAccessFranklim,Tatiany N.Freire-de-Lima,LeonardoChaves,Otávio A.LaRocque-de-Freitas,Isabel F.Silva-Trindade,Joana D. daNetto-Ferreira,José C.Freire-de-Lima,Célio G.Decoté-Ricardo,DeboraPreviato,José O.Mendonça-Previato,LuciaLima,Marco E. F. deeng2019-07-01T00:00:00Zoai:scielo:S0103-50532019000701378Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2019-07-01T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false |
dc.title.none.fl_str_mv |
Design, Synthesis, Trypanocidal Activity, and Studies on Human Album in Interaction of Novel S-Alkyl-1,2,4-triazoles |
title |
Design, Synthesis, Trypanocidal Activity, and Studies on Human Album in Interaction of Novel S-Alkyl-1,2,4-triazoles |
spellingShingle |
Design, Synthesis, Trypanocidal Activity, and Studies on Human Album in Interaction of Novel S-Alkyl-1,2,4-triazoles Franklim,Tatiany N. Trypanosoma cruzi piperine molecular hybridization 1,2,4-triazole-3-thioether human serum albumin |
title_short |
Design, Synthesis, Trypanocidal Activity, and Studies on Human Album in Interaction of Novel S-Alkyl-1,2,4-triazoles |
title_full |
Design, Synthesis, Trypanocidal Activity, and Studies on Human Album in Interaction of Novel S-Alkyl-1,2,4-triazoles |
title_fullStr |
Design, Synthesis, Trypanocidal Activity, and Studies on Human Album in Interaction of Novel S-Alkyl-1,2,4-triazoles |
title_full_unstemmed |
Design, Synthesis, Trypanocidal Activity, and Studies on Human Album in Interaction of Novel S-Alkyl-1,2,4-triazoles |
title_sort |
Design, Synthesis, Trypanocidal Activity, and Studies on Human Album in Interaction of Novel S-Alkyl-1,2,4-triazoles |
author |
Franklim,Tatiany N. |
author_facet |
Franklim,Tatiany N. Freire-de-Lima,Leonardo Chaves,Otávio A. LaRocque-de-Freitas,Isabel F. Silva-Trindade,Joana D. da Netto-Ferreira,José C. Freire-de-Lima,Célio G. Decoté-Ricardo,Debora Previato,José O. Mendonça-Previato,Lucia Lima,Marco E. F. de |
author_role |
author |
author2 |
Freire-de-Lima,Leonardo Chaves,Otávio A. LaRocque-de-Freitas,Isabel F. Silva-Trindade,Joana D. da Netto-Ferreira,José C. Freire-de-Lima,Célio G. Decoté-Ricardo,Debora Previato,José O. Mendonça-Previato,Lucia Lima,Marco E. F. de |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Franklim,Tatiany N. Freire-de-Lima,Leonardo Chaves,Otávio A. LaRocque-de-Freitas,Isabel F. Silva-Trindade,Joana D. da Netto-Ferreira,José C. Freire-de-Lima,Célio G. Decoté-Ricardo,Debora Previato,José O. Mendonça-Previato,Lucia Lima,Marco E. F. de |
dc.subject.por.fl_str_mv |
Trypanosoma cruzi piperine molecular hybridization 1,2,4-triazole-3-thioether human serum albumin |
topic |
Trypanosoma cruzi piperine molecular hybridization 1,2,4-triazole-3-thioether human serum albumin |
description |
Chagas disease is a neglected tropical disease caused by the hemoflagellated parasite Trypanosoma cruzi (Kinetoplastida). The only available drug to treat chagasic patients in Brazil, the nitroheterocycle benznidazole, is effective solely during the acute phase of the infection. There is accordingly a need to develop new therapeutic tools for the treatment of Chagas disease. This work reports the synthesis, trypanocidal evaluation and human serum albumin (HSA) interactions of a novel series of 1,2,4-triazoles. The new derivatives were synthesized via microwave irradiation in good yields. Most compounds showed toxic effects against T. cruzi with low toxicity to host cells. Three S-alkylated-triazoles showed the best activity profile against amastigotes, with half maximal inhibitory concentration (IC50) values of 3.95 ± 1.41, 4.15 ± 0.92 and 3.61 ± 0.65 µmol L-1, respectively. The interaction between HSA and 3-[(1E,3E)-4-(1,3-benzodioxol-5-yl)buta-1,3-dien-1-yl]-5-(butylthio)-4-cyclohexyl-4,5-dihydro-1H-1,2,4-triazole was investigated using multiple spectroscopic techniques and molecular docking, revealing that serum albumin is a potential endogenous carrier to this compound in the human bloodstream. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-07-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000701378 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000701378 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.21577/0103-5053.20190033 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
dc.source.none.fl_str_mv |
Journal of the Brazilian Chemical Society v.30 n.7 2019 reponame:Journal of the Brazilian Chemical Society (Online) instname:Sociedade Brasileira de Química (SBQ) instacron:SBQ |
instname_str |
Sociedade Brasileira de Química (SBQ) |
instacron_str |
SBQ |
institution |
SBQ |
reponame_str |
Journal of the Brazilian Chemical Society (Online) |
collection |
Journal of the Brazilian Chemical Society (Online) |
repository.name.fl_str_mv |
Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ) |
repository.mail.fl_str_mv |
||office@jbcs.sbq.org.br |
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1750318182041649152 |