Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruzi
Autor(a) principal: | |
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Data de Publicação: | 2014 |
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=S0103-50532014001000013 |
Resumo: | The only drugs approved for the treatment of Chagas disease, nifurtimox and benznidazole, present toxic side effects and limited efficacy in the chronic stage of the disease, which highlight the need for new drugs. Amongst the different molecular drug targets discovered in the parasite, Trypanosoma cruzi trans-sialidase (TcTS) has been considered crucial in the recognition and invasion of host cells. Hence, we report the efficient synthesis and biological evaluation (TcTS inhibition and antitrypanosomal activities) of some galactose-containing triazol-arylsulfonamides via microwave-assisted Cu(I) 1,3-dipolar azide-alkyne cycloaddition (CuAAC) based on azide benzenesulfonamides and a galactose-derived alkyne as precursors. Most of the compounds tested against TcTS showed moderate to weak inhibition (40%-15%), except one of the compounds (81%). Regarding the antitrypanosomal assay, some compounds [(IC50 70.9 µM) and (IC50 44.0 µM)] exhibited the most significant activities, although not as active as benznidazole (IC50 1.4 µM). Nevertheless, the cytotoxicity assessment showed that all compounds were not cytotoxic. In this preliminary work, we considered some compounds as lead scaffolds for further optimization. |
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Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruziChagas diseaseTrypanosoma cruzitrans-sialidasebenzenesulfonamidesclick chemistryThe only drugs approved for the treatment of Chagas disease, nifurtimox and benznidazole, present toxic side effects and limited efficacy in the chronic stage of the disease, which highlight the need for new drugs. Amongst the different molecular drug targets discovered in the parasite, Trypanosoma cruzi trans-sialidase (TcTS) has been considered crucial in the recognition and invasion of host cells. Hence, we report the efficient synthesis and biological evaluation (TcTS inhibition and antitrypanosomal activities) of some galactose-containing triazol-arylsulfonamides via microwave-assisted Cu(I) 1,3-dipolar azide-alkyne cycloaddition (CuAAC) based on azide benzenesulfonamides and a galactose-derived alkyne as precursors. Most of the compounds tested against TcTS showed moderate to weak inhibition (40%-15%), except one of the compounds (81%). Regarding the antitrypanosomal assay, some compounds [(IC50 70.9 µM) and (IC50 44.0 µM)] exhibited the most significant activities, although not as active as benznidazole (IC50 1.4 µM). Nevertheless, the cytotoxicity assessment showed that all compounds were not cytotoxic. In this preliminary work, we considered some compounds as lead scaffolds for further optimization.Sociedade Brasileira de Química2014-10-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532014001000013Journal of the Brazilian Chemical Society v.25 n.10 2014reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.5935/0103-5053.20140158info:eu-repo/semantics/openAccessJunqueira,Getúlio G.Carvalho,Marcelo R.Andrade,Peterson deLopes,Carla D.Carneiro,Zumira A.Sesti-Costa,RenataSilva,João S.Carvalho,Ivoneeng2016-08-05T00:00:00Zoai:scielo:S0103-50532014001000013Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2016-08-05T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false |
dc.title.none.fl_str_mv |
Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruzi |
title |
Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruzi |
spellingShingle |
Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruzi Junqueira,Getúlio G. Chagas disease Trypanosoma cruzi trans-sialidase benzenesulfonamides click chemistry |
title_short |
Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruzi |
title_full |
Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruzi |
title_fullStr |
Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruzi |
title_full_unstemmed |
Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruzi |
title_sort |
Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruzi |
author |
Junqueira,Getúlio G. |
author_facet |
Junqueira,Getúlio G. Carvalho,Marcelo R. Andrade,Peterson de Lopes,Carla D. Carneiro,Zumira A. Sesti-Costa,Renata Silva,João S. Carvalho,Ivone |
author_role |
author |
author2 |
Carvalho,Marcelo R. Andrade,Peterson de Lopes,Carla D. Carneiro,Zumira A. Sesti-Costa,Renata Silva,João S. Carvalho,Ivone |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Junqueira,Getúlio G. Carvalho,Marcelo R. Andrade,Peterson de Lopes,Carla D. Carneiro,Zumira A. Sesti-Costa,Renata Silva,João S. Carvalho,Ivone |
dc.subject.por.fl_str_mv |
Chagas disease Trypanosoma cruzi trans-sialidase benzenesulfonamides click chemistry |
topic |
Chagas disease Trypanosoma cruzi trans-sialidase benzenesulfonamides click chemistry |
description |
The only drugs approved for the treatment of Chagas disease, nifurtimox and benznidazole, present toxic side effects and limited efficacy in the chronic stage of the disease, which highlight the need for new drugs. Amongst the different molecular drug targets discovered in the parasite, Trypanosoma cruzi trans-sialidase (TcTS) has been considered crucial in the recognition and invasion of host cells. Hence, we report the efficient synthesis and biological evaluation (TcTS inhibition and antitrypanosomal activities) of some galactose-containing triazol-arylsulfonamides via microwave-assisted Cu(I) 1,3-dipolar azide-alkyne cycloaddition (CuAAC) based on azide benzenesulfonamides and a galactose-derived alkyne as precursors. Most of the compounds tested against TcTS showed moderate to weak inhibition (40%-15%), except one of the compounds (81%). Regarding the antitrypanosomal assay, some compounds [(IC50 70.9 µM) and (IC50 44.0 µM)] exhibited the most significant activities, although not as active as benznidazole (IC50 1.4 µM). Nevertheless, the cytotoxicity assessment showed that all compounds were not cytotoxic. In this preliminary work, we considered some compounds as lead scaffolds for further optimization. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-10-01 |
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=S0103-50532014001000013 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532014001000013 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.5935/0103-5053.20140158 |
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.25 n.10 2014 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 |
_version_ |
1750318176530333696 |