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Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit

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 sim...

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Autores principales: de Melo, Thais Regina Ferreira, Chelucci, Rafael Consolin, Pires, Maria Elisa Lopes, Dutra, Luiz Antonio, Barbieri, Karina Pereira, Bosquesi, Priscila Longhin, Trossini, Gustavo Henrique Goulart, Chung, Man Chin, dos Santos, Jean Leandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013598/
https://www.ncbi.nlm.nih.gov/pubmed/24714090
http://dx.doi.org/10.3390/ijms15045821
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author de Melo, Thais Regina Ferreira
Chelucci, Rafael Consolin
Pires, Maria Elisa Lopes
Dutra, Luiz Antonio
Barbieri, Karina Pereira
Bosquesi, Priscila Longhin
Trossini, Gustavo Henrique Goulart
Chung, Man Chin
dos Santos, Jean Leandro
author_facet de Melo, Thais Regina Ferreira
Chelucci, Rafael Consolin
Pires, Maria Elisa Lopes
Dutra, Luiz Antonio
Barbieri, Karina Pereira
Bosquesi, Priscila Longhin
Trossini, Gustavo Henrique Goulart
Chung, Man Chin
dos Santos, Jean Leandro
author_sort de Melo, Thais Regina Ferreira
collection PubMed
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.
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spelling pubmed-40135982014-05-08 Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit de Melo, Thais Regina Ferreira Chelucci, Rafael Consolin Pires, Maria Elisa Lopes Dutra, Luiz Antonio Barbieri, Karina Pereira Bosquesi, Priscila Longhin Trossini, Gustavo Henrique Goulart Chung, Man Chin dos Santos, Jean Leandro Int J Mol Sci Article 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. Molecular Diversity Preservation International (MDPI) 2014-04-04 /pmc/articles/PMC4013598/ /pubmed/24714090 http://dx.doi.org/10.3390/ijms15045821 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
de Melo, Thais Regina Ferreira
Chelucci, Rafael Consolin
Pires, Maria Elisa Lopes
Dutra, Luiz Antonio
Barbieri, Karina Pereira
Bosquesi, Priscila Longhin
Trossini, Gustavo Henrique Goulart
Chung, Man Chin
dos Santos, Jean Leandro
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
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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013598/
https://www.ncbi.nlm.nih.gov/pubmed/24714090
http://dx.doi.org/10.3390/ijms15045821
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