Synthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.1590/s2175-97902017000116067 http://hdl.handle.net/1843/56623 https://orcid.org/0000-0002-8887-8859 https://orcid.org/0000-0002-6681-9014 https://orcid.org/0000-0002-1666-4421 |
Resumo: | We describe herein the synthesis and evaluation of the antileishmanial activity against promastigote forms of Leishmania amazonensis and cytotoxicity to murine macrophages of a series of 2-chloro-Narylacetamide derivatives. All compounds were active, except one (compound 3). Compound 5 presented the most promising results, showing good antileishmanial activity (CI50=5.39±0.67 µM) and moderate selectivity (SI=6.36), indicating that further development of this class is worthwhile. Preliminary QSAR studies, although not predictive, furnished some insights on the importance of electronic character of aryl substituent to biological activity, as well as an indirect influence of hydrophobicity on activity. |
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2023-07-18T20:12:17Z2023-07-18T20:12:17Z2017531https://doi.org/10.1590/s2175-979020170001160672175-9790http://hdl.handle.net/1843/56623https://orcid.org/0000-0002-8887-8859https://orcid.org/0000-0002-6681-9014https://orcid.org/0000-0002-1666-4421We describe herein the synthesis and evaluation of the antileishmanial activity against promastigote forms of Leishmania amazonensis and cytotoxicity to murine macrophages of a series of 2-chloro-Narylacetamide derivatives. All compounds were active, except one (compound 3). Compound 5 presented the most promising results, showing good antileishmanial activity (CI50=5.39±0.67 µM) and moderate selectivity (SI=6.36), indicating that further development of this class is worthwhile. Preliminary QSAR studies, although not predictive, furnished some insights on the importance of electronic character of aryl substituent to biological activity, as well as an indirect influence of hydrophobicity on activity.Descrevemos aqui a síntese e avaliação da atividade antileishmania contra formas promastigotas de Leishmania amazonensis e citotoxicidade para macrófagos murinos de uma série de derivados de 2-cloro-narilacetamida. Todos os compostos foram ativos, exceto um (composto 3). O composto 5 apresentou os resultados mais promissores, mostrando boa atividade antileishmania (IC50=5,39±0,67 µM) e seletividade moderada (SI=6,36), indicando que o desenvolvimento desta classe vale a pena. Estudos QSAR preliminares, embora não preditivos, forneceram alguns insights sobre a importância do caráter eletrônico do substituinte arila para a atividade biológica, bem como uma influência indireta da hidrofobicidade na atividade.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorOutra AgênciaengUniversidade Federal de Minas GeraisUFMGBrasilCOLTEC - COLEGIO TECNICOFAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOSBrazilian Journal of Pharmaceutical SciencesLeishmania mexicanaTestes imunológicos de citotoxicidadeLeishmaniasis/treatmentChloroacetamidesLeishmania amazonensisChloroacetamides/QSARSynthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamidesSíntese, atividade antileishmania e estudos QSAR de 2-cloro-N-arilacetamidasinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.scielo.br/j/bjps/a/zCqG5bQsWpd7R3PbzBKP5Qf/?lang=en#Stefânia Neiva LavoratoMariana Costa DuartePedro Henrique Rocha de AndradeEduardo Antônio Ferraz CoelhoRicardo José Alvesapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/56623/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALSynthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides.pdfSynthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides.pdfapplication/pdf313044https://repositorio.ufmg.br/bitstream/1843/56623/2/Synthesis%2c%20antileishmanial%20activity%20and%20QSAR%20studies%20of%20%202%e2%80%91chloro%e2%80%91N%e2%80%91arylacetamides.pdf3ccf6875e93f6b41577084adfa18293dMD521843/566232023-07-18 17:12:17.155oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-07-18T20:12:17Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Synthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides |
dc.title.alternative.pt_BR.fl_str_mv |
Síntese, atividade antileishmania e estudos QSAR de 2-cloro-N-arilacetamidas |
title |
Synthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides |
spellingShingle |
Synthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides Stefânia Neiva Lavorato Leishmaniasis/treatment Chloroacetamides Leishmania amazonensis Chloroacetamides/QSAR Leishmania mexicana Testes imunológicos de citotoxicidade |
title_short |
Synthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides |
title_full |
Synthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides |
title_fullStr |
Synthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides |
title_full_unstemmed |
Synthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides |
title_sort |
Synthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides |
author |
Stefânia Neiva Lavorato |
author_facet |
Stefânia Neiva Lavorato Mariana Costa Duarte Pedro Henrique Rocha de Andrade Eduardo Antônio Ferraz Coelho Ricardo José Alves |
author_role |
author |
author2 |
Mariana Costa Duarte Pedro Henrique Rocha de Andrade Eduardo Antônio Ferraz Coelho Ricardo José Alves |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Stefânia Neiva Lavorato Mariana Costa Duarte Pedro Henrique Rocha de Andrade Eduardo Antônio Ferraz Coelho Ricardo José Alves |
dc.subject.por.fl_str_mv |
Leishmaniasis/treatment Chloroacetamides Leishmania amazonensis Chloroacetamides/QSAR |
topic |
Leishmaniasis/treatment Chloroacetamides Leishmania amazonensis Chloroacetamides/QSAR Leishmania mexicana Testes imunológicos de citotoxicidade |
dc.subject.other.pt_BR.fl_str_mv |
Leishmania mexicana Testes imunológicos de citotoxicidade |
description |
We describe herein the synthesis and evaluation of the antileishmanial activity against promastigote forms of Leishmania amazonensis and cytotoxicity to murine macrophages of a series of 2-chloro-Narylacetamide derivatives. All compounds were active, except one (compound 3). Compound 5 presented the most promising results, showing good antileishmanial activity (CI50=5.39±0.67 µM) and moderate selectivity (SI=6.36), indicating that further development of this class is worthwhile. Preliminary QSAR studies, although not predictive, furnished some insights on the importance of electronic character of aryl substituent to biological activity, as well as an indirect influence of hydrophobicity on activity. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2023-07-18T20:12:17Z |
dc.date.available.fl_str_mv |
2023-07-18T20:12:17Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/56623 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1590/s2175-97902017000116067 |
dc.identifier.issn.pt_BR.fl_str_mv |
2175-9790 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0002-8887-8859 https://orcid.org/0000-0002-6681-9014 https://orcid.org/0000-0002-1666-4421 |
url |
https://doi.org/10.1590/s2175-97902017000116067 http://hdl.handle.net/1843/56623 https://orcid.org/0000-0002-8887-8859 https://orcid.org/0000-0002-6681-9014 https://orcid.org/0000-0002-1666-4421 |
identifier_str_mv |
2175-9790 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Brazilian Journal of Pharmaceutical Sciences |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.publisher.initials.fl_str_mv |
UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
COLTEC - COLEGIO TECNICO FAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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Universidade Federal de Minas Gerais (UFMG) |
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UFMG |
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UFMG |
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Repositório Institucional da UFMG |
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