Synthesis, antileishmanial activity and QSAR studies of 2‑chloro‑N‑arylacetamides

Detalhes bibliográficos
Autor(a) principal: Stefânia Neiva Lavorato
Data de Publicação: 2017
Outros Autores: Mariana Costa Duarte, Pedro Henrique Rocha de Andrade, Eduardo Antônio Ferraz Coelho, Ricardo José Alves
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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spelling 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
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
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