Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruzi

Detalhes bibliográficos
Autor(a) principal: Junqueira,Getúlio G.
Data de Publicação: 2014
Outros Autores: Carvalho,Marcelo R., Andrade,Peterson de, Lopes,Carla D., Carneiro,Zumira A., Sesti-Costa,Renata, Silva,João S., Carvalho,Ivone
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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spelling 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
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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
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