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Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice
Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612535/ https://www.ncbi.nlm.nih.gov/pubmed/34818331 http://dx.doi.org/10.1371/journal.pone.0258094 |
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author | Medeiros, Maria Alice Miranda Bezerra Gama e Silva, Mariana de Menezes Barbosa, Jackson Martins de Lavor, Érica Ribeiro, Tiago Feitosa Macedo, Cícero André Ferreira de Souza Duarte-Filho, Luiz Antonio Miranda Feitosa, Thiala Alves de Jesus Silva, Jussara Fokoue, Harold Hilarion Araújo, Cleônia Roberta Melo de Assis Gonsalves, Arlan Augusto de Araújo Ribeiro, Luciano Almeida, Jackson Roberto Guedes da Silva |
author_facet | Medeiros, Maria Alice Miranda Bezerra Gama e Silva, Mariana de Menezes Barbosa, Jackson Martins de Lavor, Érica Ribeiro, Tiago Feitosa Macedo, Cícero André Ferreira de Souza Duarte-Filho, Luiz Antonio Miranda Feitosa, Thiala Alves de Jesus Silva, Jussara Fokoue, Harold Hilarion Araújo, Cleônia Roberta Melo de Assis Gonsalves, Arlan Augusto de Araújo Ribeiro, Luciano Almeida, Jackson Roberto Guedes da Silva |
author_sort | Medeiros, Maria Alice Miranda Bezerra |
collection | PubMed |
description | Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R(1)R(2)C = NNR(3)R(4), were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug. |
format | Online Article Text |
id | pubmed-8612535 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-86125352021-11-25 Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice Medeiros, Maria Alice Miranda Bezerra Gama e Silva, Mariana de Menezes Barbosa, Jackson Martins de Lavor, Érica Ribeiro, Tiago Feitosa Macedo, Cícero André Ferreira de Souza Duarte-Filho, Luiz Antonio Miranda Feitosa, Thiala Alves de Jesus Silva, Jussara Fokoue, Harold Hilarion Araújo, Cleônia Roberta Melo de Assis Gonsalves, Arlan Augusto de Araújo Ribeiro, Luciano Almeida, Jackson Roberto Guedes da Silva PLoS One Research Article Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R(1)R(2)C = NNR(3)R(4), were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug. Public Library of Science 2021-11-24 /pmc/articles/PMC8612535/ /pubmed/34818331 http://dx.doi.org/10.1371/journal.pone.0258094 Text en © 2021 Medeiros et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Medeiros, Maria Alice Miranda Bezerra Gama e Silva, Mariana de Menezes Barbosa, Jackson Martins de Lavor, Érica Ribeiro, Tiago Feitosa Macedo, Cícero André Ferreira de Souza Duarte-Filho, Luiz Antonio Miranda Feitosa, Thiala Alves de Jesus Silva, Jussara Fokoue, Harold Hilarion Araújo, Cleônia Roberta Melo de Assis Gonsalves, Arlan Augusto de Araújo Ribeiro, Luciano Almeida, Jackson Roberto Guedes da Silva Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice |
title | Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice |
title_full | Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice |
title_fullStr | Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice |
title_full_unstemmed | Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice |
title_short | Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice |
title_sort | antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612535/ https://www.ncbi.nlm.nih.gov/pubmed/34818331 http://dx.doi.org/10.1371/journal.pone.0258094 |
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