Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids

ABSTRACT: The synthesis and biological activities (cytotoxicity, leishmanicidal, and trypanocidal) of 11 triclosan–hydrazone hybrids are described herein. The structure of the products was elucidated by spectral data (NMR, IR) and mass spectrometric analyses. The synthesized compounds were evaluated...

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Autores:
Vergara Guira, Sebastian
Carda, Miguel
Agut, Raül
Yepes Daza, Lina Marcela
Vélez Bernal, Iván Darío
Robledo Restrepo, Sara María
Cardona Galeano, Wilson
Tipo de recurso:
Article of investigation
Fecha de publicación:
2017
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/23345
Acceso en línea:
http://hdl.handle.net/10495/23345
Palabra clave:
Leishmaniasis
Enfermedad de Chagas
Chagas Disease
Trypanosoma cruzi
Triclosán
Triclosan
Rights
openAccess
License
http://creativecommons.org/licenses/by/2.5/co/
id UDEA2_a09ce02fd9fd1f4a63d7d6a3a6b17cf6
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/23345
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids
title Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids
spellingShingle Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids
Leishmaniasis
Enfermedad de Chagas
Chagas Disease
Trypanosoma cruzi
Triclosán
Triclosan
title_short Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids
title_full Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids
title_fullStr Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids
title_full_unstemmed Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids
title_sort Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids
dc.creator.fl_str_mv Vergara Guira, Sebastian
Carda, Miguel
Agut, Raül
Yepes Daza, Lina Marcela
Vélez Bernal, Iván Darío
Robledo Restrepo, Sara María
Cardona Galeano, Wilson
dc.contributor.author.none.fl_str_mv Vergara Guira, Sebastian
Carda, Miguel
Agut, Raül
Yepes Daza, Lina Marcela
Vélez Bernal, Iván Darío
Robledo Restrepo, Sara María
Cardona Galeano, Wilson
dc.subject.decs.none.fl_str_mv Leishmaniasis
Enfermedad de Chagas
Chagas Disease
Trypanosoma cruzi
Triclosán
Triclosan
topic Leishmaniasis
Enfermedad de Chagas
Chagas Disease
Trypanosoma cruzi
Triclosán
Triclosan
description ABSTRACT: The synthesis and biological activities (cytotoxicity, leishmanicidal, and trypanocidal) of 11 triclosan–hydrazone hybrids are described herein. The structure of the products was elucidated by spectral data (NMR, IR) and mass spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leish-mania species in Colombia, and against Trypanosoma cruzi, which is the major pathogenic species to Chagas disease in humans. In addition, the cytotoxic activity of the synthesized compounds was evaluated against human U- 937 macrophages. Hydrazone hybrids were obtained as Esynperiplanar and E-antiperiplanar conformers. Nine of them were active against L. (V) panamensis (5a–5d, 5f–5j) and eight of them against T. cruzi (5a, 5c, 5d, 5f–5j), with EC50 values lower than 40 μM. The compounds 5c, 5e, and 5h exhibit the best selectivity index against both L. (V) panamensis and T. cruzi, with values ranging from 5.90 to 16.55, thus showing potential as starting compounds for the eventual development of drugs against these parasites. The presence of hydroxy or methoxy groups in positions 2 and 4 of the aromatic ring of the benzylidene moiety increases both activity and cytotoxicity. There is no clear relationship between the antiprotozoal activity and the methylation pattern of the hydroxy groups, since in some cases methylation decreases the activity (5d vs. 5g) while in other cases the activity is increased (5c vs. 5f and 5i vs. 5j).
publishDate 2017
dc.date.issued.none.fl_str_mv 2017
dc.date.accessioned.none.fl_str_mv 2021-10-21T15:04:37Z
dc.date.available.none.fl_str_mv 2021-10-21T15:04:37Z
dc.type.spa.fl_str_mv info:eu-repo/semantics/article
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dc.type.hasversion.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/ART
dc.type.local.spa.fl_str_mv Artículo de investigación
format http://purl.org/coar/resource_type/c_2df8fbb1
status_str publishedVersion
dc.identifier.issn.none.fl_str_mv 1054-2523
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/10495/23345
dc.identifier.doi.none.fl_str_mv 10.1007/s00044-017-2019-2
dc.identifier.eissn.none.fl_str_mv 1554-8120
identifier_str_mv 1054-2523
10.1007/s00044-017-2019-2
1554-8120
url http://hdl.handle.net/10495/23345
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Med. Chem. Res.
dc.rights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by/2.5/co/
dc.rights.accessrights.spa.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.creativecommons.spa.fl_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/2.5/co/
http://purl.org/coar/access_right/c_abf2
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dc.format.extent.spa.fl_str_mv 12
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Springer
dc.publisher.group.spa.fl_str_mv Programa de Estudio y Control de Enfermedades Tropicales (PECET)
Química de Plantas Colombianas
dc.publisher.place.spa.fl_str_mv Nueva York, Estados Unidos
institution Universidad de Antioquia
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http://bibliotecadigital.udea.edu.co/bitstream/10495/23345/2/license.txt
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spelling Vergara Guira, SebastianCarda, MiguelAgut, RaülYepes Daza, Lina MarcelaVélez Bernal, Iván DaríoRobledo Restrepo, Sara MaríaCardona Galeano, Wilson2021-10-21T15:04:37Z2021-10-21T15:04:37Z20171054-2523http://hdl.handle.net/10495/2334510.1007/s00044-017-2019-21554-8120ABSTRACT: The synthesis and biological activities (cytotoxicity, leishmanicidal, and trypanocidal) of 11 triclosan–hydrazone hybrids are described herein. The structure of the products was elucidated by spectral data (NMR, IR) and mass spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leish-mania species in Colombia, and against Trypanosoma cruzi, which is the major pathogenic species to Chagas disease in humans. In addition, the cytotoxic activity of the synthesized compounds was evaluated against human U- 937 macrophages. Hydrazone hybrids were obtained as Esynperiplanar and E-antiperiplanar conformers. Nine of them were active against L. (V) panamensis (5a–5d, 5f–5j) and eight of them against T. cruzi (5a, 5c, 5d, 5f–5j), with EC50 values lower than 40 μM. The compounds 5c, 5e, and 5h exhibit the best selectivity index against both L. (V) panamensis and T. cruzi, with values ranging from 5.90 to 16.55, thus showing potential as starting compounds for the eventual development of drugs against these parasites. The presence of hydroxy or methoxy groups in positions 2 and 4 of the aromatic ring of the benzylidene moiety increases both activity and cytotoxicity. There is no clear relationship between the antiprotozoal activity and the methylation pattern of the hydroxy groups, since in some cases methylation decreases the activity (5d vs. 5g) while in other cases the activity is increased (5c vs. 5f and 5i vs. 5j).COL0015099COL001532912application/pdfengSpringerPrograma de Estudio y Control de Enfermedades Tropicales (PECET)Química de Plantas ColombianasNueva York, Estados Unidosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/2.5/co/http://purl.org/coar/access_right/c_abf2https://creativecommons.org/licenses/by/4.0/Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybridsLeishmaniasisEnfermedad de ChagasChagas DiseaseTrypanosoma cruziTriclosánTriclosanMed. Chem. Res.Medicinal Chemistry Research112CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8927http://bibliotecadigital.udea.edu.co/bitstream/10495/23345/1/license_rdf1646d1f6b96dbbbc38035efc9239ac9cMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://bibliotecadigital.udea.edu.co/bitstream/10495/23345/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52ORIGINALVergaraSebastian_2017_SynthesisAntiprotozoal.pdfVergaraSebastian_2017_SynthesisAntiprotozoal.pdfArtículo de investigaciónapplication/pdf872680http://bibliotecadigital.udea.edu.co/bitstream/10495/23345/3/VergaraSebastian_2017_SynthesisAntiprotozoal.pdf7b81573efb336a09fe2f8e5323cbfa2aMD5310495/23345oai:bibliotecadigital.udea.edu.co:10495/233452021-10-21 10:04:38.294Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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