Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunit
Autor(a) principal: | |
---|---|
Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/ijms15045821 http://hdl.handle.net/11449/133754 |
Resumo: | A series of anti-inflammatory derivatives containing an N-acyl hydrazone subunit (4a–e) were synthesized and characterized. Docking studies were performed that suggest that compounds 4a–e bind to cyclooxygenase (COX)-1 and COX-2 isoforms, but with higher affinity for COX-2. The compounds display similar anti-inflammatory activities in vivo, although compound 4c is the most effective compound for inhibiting rat paw edema, with a reduction in the extent of inflammation of 35.9% and 52.8% at 2 and 4 h, respectively. The anti-inflammatory activity of N-acyl hydrazone derivatives was inferior to their respective parent drugs, except for compound 4c after 5 h. Ulcerogenic studies revealed that compounds 4a–e are less gastrotoxic than the respective parent drug. Compounds 4b–e demonstrated mucosal damage comparable to celecoxib. The in vivo analgesic activities of the compounds are higher than the respective parent drug for compounds 4a–b and 4d–e. Compound 4a was more active than dipyrone in reducing acetic-acid-induced abdominal constrictions. Our results indicate that compounds 4a–e are anti-inflammatory and analgesic compounds with reduced gastrotoxicity compared to their respective parent non-steroidal anti-inflammatory drugs. |
id |
UNSP_2774b1ee13fabdc81274dc931a7604a5 |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/133754 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunitAnti-inflammatoryAnalgesicHydrazoneMolecular hybridizationNon-steroidalAnti-inflammatoryNSAIDDockingMolecular modelingCOXA series of anti-inflammatory derivatives containing an N-acyl hydrazone subunit (4a–e) were synthesized and characterized. Docking studies were performed that suggest that compounds 4a–e bind to cyclooxygenase (COX)-1 and COX-2 isoforms, but with higher affinity for COX-2. The compounds display similar anti-inflammatory activities in vivo, although compound 4c is the most effective compound for inhibiting rat paw edema, with a reduction in the extent of inflammation of 35.9% and 52.8% at 2 and 4 h, respectively. The anti-inflammatory activity of N-acyl hydrazone derivatives was inferior to their respective parent drugs, except for compound 4c after 5 h. Ulcerogenic studies revealed that compounds 4a–e are less gastrotoxic than the respective parent drug. Compounds 4b–e demonstrated mucosal damage comparable to celecoxib. The in vivo analgesic activities of the compounds are higher than the respective parent drug for compounds 4a–b and 4d–e. Compound 4a was more active than dipyrone in reducing acetic-acid-induced abdominal constrictions. Our results indicate that compounds 4a–e are anti-inflammatory and analgesic compounds with reduced gastrotoxicity compared to their respective parent non-steroidal anti-inflammatory drugs.Universidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Fármacos e Médicamentos, Faculdade de Ciências Farmacêuticas de Araraquara, Araraquara, Rodovia Araraquara-Jaú Km. 01, Campus Ville, CEP 14801902, SP, BrasilFaculty of Pharmaceutical Science, University of São Paulo, Av. Professor Lineu Prestes 580, São Paulo 05508-900, SP, BrazilUniversidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Fármacos e Médicamentos, Faculdade de Ciências Farmacêuticas de Araraquara, Araraquara, Rodovia Araraquara-Jaú Km. 01, Campus Ville, CEP 14801902, SP, BrasilUniversidade Estadual Paulista (Unesp)|Universidade de São Paulo (USP)Melo, Thais Regina Ferreira de [UNESP]Chelucci, Rafael Consolin [UNESP]Pires, Maria Elisa Lopes [UNESP]Dutra, Luiz Antonio [UNESP]Barbieri, Karina Pereira [UNESP]Bosquesi, Priscila Longhin [UNESP]Trossini, Gustavo Henrique GoulartChung, Man Chin [UNESP]Santos, Jean Leandro dos [UNESP]2016-01-28T16:56:29Z2016-01-28T16:56:29Z2014info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article5821-5837application/pdfhttp://dx.doi.org/10.3390/ijms15045821International Journal of Molecular Sciences, v. 15, n. 4, p. 5821-5837, 2014.1422-0067http://hdl.handle.net/11449/13375410.3390/ijms15045821ISSN1422-0067-2014-15-04-5821-5837.pdf5178218874772717973433360797541357379336395169440000-0003-4141-0455Currículo Lattesreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Molecular Sciences3.6871,260info:eu-repo/semantics/openAccess2024-06-24T13:44:53Zoai:repositorio.unesp.br:11449/133754Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T13:58:52.272443Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunit |
title |
Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunit |
spellingShingle |
Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunit Melo, Thais Regina Ferreira de [UNESP] Anti-inflammatory Analgesic Hydrazone Molecular hybridization Non-steroidal Anti-inflammatory NSAID Docking Molecular modeling COX |
title_short |
Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunit |
title_full |
Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunit |
title_fullStr |
Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunit |
title_full_unstemmed |
Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunit |
title_sort |
Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunit |
author |
Melo, Thais Regina Ferreira de [UNESP] |
author_facet |
Melo, Thais Regina Ferreira de [UNESP] Chelucci, Rafael Consolin [UNESP] Pires, Maria Elisa Lopes [UNESP] Dutra, Luiz Antonio [UNESP] Barbieri, Karina Pereira [UNESP] Bosquesi, Priscila Longhin [UNESP] Trossini, Gustavo Henrique Goulart Chung, Man Chin [UNESP] Santos, Jean Leandro dos [UNESP] |
author_role |
author |
author2 |
Chelucci, Rafael Consolin [UNESP] Pires, Maria Elisa Lopes [UNESP] Dutra, Luiz Antonio [UNESP] Barbieri, Karina Pereira [UNESP] Bosquesi, Priscila Longhin [UNESP] Trossini, Gustavo Henrique Goulart Chung, Man Chin [UNESP] Santos, Jean Leandro dos [UNESP] |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp)|Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Melo, Thais Regina Ferreira de [UNESP] Chelucci, Rafael Consolin [UNESP] Pires, Maria Elisa Lopes [UNESP] Dutra, Luiz Antonio [UNESP] Barbieri, Karina Pereira [UNESP] Bosquesi, Priscila Longhin [UNESP] Trossini, Gustavo Henrique Goulart Chung, Man Chin [UNESP] Santos, Jean Leandro dos [UNESP] |
dc.subject.por.fl_str_mv |
Anti-inflammatory Analgesic Hydrazone Molecular hybridization Non-steroidal Anti-inflammatory NSAID Docking Molecular modeling COX |
topic |
Anti-inflammatory Analgesic Hydrazone Molecular hybridization Non-steroidal Anti-inflammatory NSAID Docking Molecular modeling COX |
description |
A series of anti-inflammatory derivatives containing an N-acyl hydrazone subunit (4a–e) were synthesized and characterized. Docking studies were performed that suggest that compounds 4a–e bind to cyclooxygenase (COX)-1 and COX-2 isoforms, but with higher affinity for COX-2. The compounds display similar anti-inflammatory activities in vivo, although compound 4c is the most effective compound for inhibiting rat paw edema, with a reduction in the extent of inflammation of 35.9% and 52.8% at 2 and 4 h, respectively. The anti-inflammatory activity of N-acyl hydrazone derivatives was inferior to their respective parent drugs, except for compound 4c after 5 h. Ulcerogenic studies revealed that compounds 4a–e are less gastrotoxic than the respective parent drug. Compounds 4b–e demonstrated mucosal damage comparable to celecoxib. The in vivo analgesic activities of the compounds are higher than the respective parent drug for compounds 4a–b and 4d–e. Compound 4a was more active than dipyrone in reducing acetic-acid-induced abdominal constrictions. Our results indicate that compounds 4a–e are anti-inflammatory and analgesic compounds with reduced gastrotoxicity compared to their respective parent non-steroidal anti-inflammatory drugs. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014 2016-01-28T16:56:29Z 2016-01-28T16:56:29Z |
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/ijms15045821 International Journal of Molecular Sciences, v. 15, n. 4, p. 5821-5837, 2014. 1422-0067 http://hdl.handle.net/11449/133754 10.3390/ijms15045821 ISSN1422-0067-2014-15-04-5821-5837.pdf 5178218874772717 9734333607975413 5737933639516944 0000-0003-4141-0455 |
url |
http://dx.doi.org/10.3390/ijms15045821 http://hdl.handle.net/11449/133754 |
identifier_str_mv |
International Journal of Molecular Sciences, v. 15, n. 4, p. 5821-5837, 2014. 1422-0067 10.3390/ijms15045821 ISSN1422-0067-2014-15-04-5821-5837.pdf 5178218874772717 9734333607975413 5737933639516944 0000-0003-4141-0455 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Molecular Sciences 3.687 1,260 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
5821-5837 application/pdf |
dc.source.none.fl_str_mv |
Currículo Lattes 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_ |
1808128299542511616 |