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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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