Synthesis, Characterization and Pharmacological Evaluation of 1-(2-Chloro-6-Fluorophenyl)-5-Methylindolin-2-One: A New Anti-Inflammatory Compound with Reduced Gastric Ulceration Properties

Detalhes bibliográficos
Autor(a) principal: dos Santos, Jean Leandro [UNESP]
Data de Publicação: 2010
Outros Autores: Chelucci, Rafael [UNESP], Chiquetto, Richard [UNESP], Chin, Chung Man [UNESP], Campos, Michel Leandro [UNESP], Peccinini, Rosangela Goncalves [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3390/molecules15118039
http://hdl.handle.net/11449/7776
Resumo: The new compound 1-(2-chloro-6-fluorophenyl)-5-methylindolin-2-one (1), designed using the prodrug approach, was easily obtained in 85% yield and characterized by nuclear magnetic resonance, elemental analysis, mass spectrometry and infrared spectroscopy. The lactam 1 showed anti-inflammatory and analgesic activity comparable to that of the COX-2 inhibitor lumiracoxib, without gastro-ulceration effects. Stability studies demonstrated that the lactam function was stable and did not hydrolyze in pH 1.2 or 7.4. Furthermore, using a thioglycollate-induced peritonitis model, compound 1 was shown to inhibit cell migration by 50.4%, while lumiracoxib inhibited it by 18%. This compound represents a new non-ulcerogenic prototype for the treatment of chronic inflammatory diseases.
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spelling Synthesis, Characterization and Pharmacological Evaluation of 1-(2-Chloro-6-Fluorophenyl)-5-Methylindolin-2-One: A New Anti-Inflammatory Compound with Reduced Gastric Ulceration Propertiespro-druglactamlumiracoxibanti-inflammatoryThe new compound 1-(2-chloro-6-fluorophenyl)-5-methylindolin-2-one (1), designed using the prodrug approach, was easily obtained in 85% yield and characterized by nuclear magnetic resonance, elemental analysis, mass spectrometry and infrared spectroscopy. The lactam 1 showed anti-inflammatory and analgesic activity comparable to that of the COX-2 inhibitor lumiracoxib, without gastro-ulceration effects. Stability studies demonstrated that the lactam function was stable and did not hydrolyze in pH 1.2 or 7.4. Furthermore, using a thioglycollate-induced peritonitis model, compound 1 was shown to inhibit cell migration by 50.4%, while lumiracoxib inhibited it by 18%. This compound represents a new non-ulcerogenic prototype for the treatment of chronic inflammatory diseases.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)UNESP, Fac Ciencias Farmaceut, Dept Farmacos & Medicamentos, Lab Pesquisa & Desenvolvimento Farmacos, BR-14801902 Araraquara, SP, BrazilUNESP, Fac Ciencias Farmaceut, Dept Principios Ativos Nat & Toxicol, BR-14801902 Araraquara, SP, BrazilUNESP, Fac Ciencias Farmaceut, Dept Farmacos & Medicamentos, Lab Pesquisa & Desenvolvimento Farmacos, BR-14801902 Araraquara, SP, BrazilUNESP, Fac Ciencias Farmaceut, Dept Principios Ativos Nat & Toxicol, BR-14801902 Araraquara, SP, BrazilMdpi AgUniversidade Estadual Paulista (Unesp)dos Santos, Jean Leandro [UNESP]Chelucci, Rafael [UNESP]Chiquetto, Richard [UNESP]Chin, Chung Man [UNESP]Campos, Michel Leandro [UNESP]Peccinini, Rosangela Goncalves [UNESP]2014-05-20T13:24:46Z2014-05-20T13:24:46Z2010-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article8039-8047application/pdfhttp://dx.doi.org/10.3390/molecules15118039Molecules. Basel: Mdpi Ag, v. 15, n. 11, p. 8039-8047, 2010.1420-3049http://hdl.handle.net/11449/777610.3390/molecules15118039WOS:000284582100034WOS000284582100034.pdf973433360797541310667434239290930000-0003-4141-0455Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMolecules3.0980,855info:eu-repo/semantics/openAccess2024-06-24T14:51:52Zoai:repositorio.unesp.br:11449/7776Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:42:29.980655Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Synthesis, Characterization and Pharmacological Evaluation of 1-(2-Chloro-6-Fluorophenyl)-5-Methylindolin-2-One: A New Anti-Inflammatory Compound with Reduced Gastric Ulceration Properties
title Synthesis, Characterization and Pharmacological Evaluation of 1-(2-Chloro-6-Fluorophenyl)-5-Methylindolin-2-One: A New Anti-Inflammatory Compound with Reduced Gastric Ulceration Properties
spellingShingle Synthesis, Characterization and Pharmacological Evaluation of 1-(2-Chloro-6-Fluorophenyl)-5-Methylindolin-2-One: A New Anti-Inflammatory Compound with Reduced Gastric Ulceration Properties
dos Santos, Jean Leandro [UNESP]
pro-drug
lactam
lumiracoxib
anti-inflammatory
title_short Synthesis, Characterization and Pharmacological Evaluation of 1-(2-Chloro-6-Fluorophenyl)-5-Methylindolin-2-One: A New Anti-Inflammatory Compound with Reduced Gastric Ulceration Properties
title_full Synthesis, Characterization and Pharmacological Evaluation of 1-(2-Chloro-6-Fluorophenyl)-5-Methylindolin-2-One: A New Anti-Inflammatory Compound with Reduced Gastric Ulceration Properties
title_fullStr Synthesis, Characterization and Pharmacological Evaluation of 1-(2-Chloro-6-Fluorophenyl)-5-Methylindolin-2-One: A New Anti-Inflammatory Compound with Reduced Gastric Ulceration Properties
title_full_unstemmed Synthesis, Characterization and Pharmacological Evaluation of 1-(2-Chloro-6-Fluorophenyl)-5-Methylindolin-2-One: A New Anti-Inflammatory Compound with Reduced Gastric Ulceration Properties
title_sort Synthesis, Characterization and Pharmacological Evaluation of 1-(2-Chloro-6-Fluorophenyl)-5-Methylindolin-2-One: A New Anti-Inflammatory Compound with Reduced Gastric Ulceration Properties
author dos Santos, Jean Leandro [UNESP]
author_facet dos Santos, Jean Leandro [UNESP]
Chelucci, Rafael [UNESP]
Chiquetto, Richard [UNESP]
Chin, Chung Man [UNESP]
Campos, Michel Leandro [UNESP]
Peccinini, Rosangela Goncalves [UNESP]
author_role author
author2 Chelucci, Rafael [UNESP]
Chiquetto, Richard [UNESP]
Chin, Chung Man [UNESP]
Campos, Michel Leandro [UNESP]
Peccinini, Rosangela Goncalves [UNESP]
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv dos Santos, Jean Leandro [UNESP]
Chelucci, Rafael [UNESP]
Chiquetto, Richard [UNESP]
Chin, Chung Man [UNESP]
Campos, Michel Leandro [UNESP]
Peccinini, Rosangela Goncalves [UNESP]
dc.subject.por.fl_str_mv pro-drug
lactam
lumiracoxib
anti-inflammatory
topic pro-drug
lactam
lumiracoxib
anti-inflammatory
description The new compound 1-(2-chloro-6-fluorophenyl)-5-methylindolin-2-one (1), designed using the prodrug approach, was easily obtained in 85% yield and characterized by nuclear magnetic resonance, elemental analysis, mass spectrometry and infrared spectroscopy. The lactam 1 showed anti-inflammatory and analgesic activity comparable to that of the COX-2 inhibitor lumiracoxib, without gastro-ulceration effects. Stability studies demonstrated that the lactam function was stable and did not hydrolyze in pH 1.2 or 7.4. Furthermore, using a thioglycollate-induced peritonitis model, compound 1 was shown to inhibit cell migration by 50.4%, while lumiracoxib inhibited it by 18%. This compound represents a new non-ulcerogenic prototype for the treatment of chronic inflammatory diseases.
publishDate 2010
dc.date.none.fl_str_mv 2010-11-01
2014-05-20T13:24:46Z
2014-05-20T13:24:46Z
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://dx.doi.org/10.3390/molecules15118039
Molecules. Basel: Mdpi Ag, v. 15, n. 11, p. 8039-8047, 2010.
1420-3049
http://hdl.handle.net/11449/7776
10.3390/molecules15118039
WOS:000284582100034
WOS000284582100034.pdf
9734333607975413
1066743423929093
0000-0003-4141-0455
url http://dx.doi.org/10.3390/molecules15118039
http://hdl.handle.net/11449/7776
identifier_str_mv Molecules. Basel: Mdpi Ag, v. 15, n. 11, p. 8039-8047, 2010.
1420-3049
10.3390/molecules15118039
WOS:000284582100034
WOS000284582100034.pdf
9734333607975413
1066743423929093
0000-0003-4141-0455
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Molecules
3.098
0,855
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 8039-8047
application/pdf
dc.publisher.none.fl_str_mv Mdpi Ag
publisher.none.fl_str_mv Mdpi Ag
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
_version_ 1808129108548255744

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