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:	Maria Alice Miranda Bezerra Medeiros, Mariana Gama E Silva, Jackson de Menezes Barbosa, Érica Martins de Lavor, Tiago Feitosa Ribeiro, Cícero André Ferreira Macedo, Luiz Antonio Miranda de Souza Duarte-Filho, Thiala Alves Feitosa, Jussara de Jesus Silva, Harold Hilarion Fokoue, Cleônia Roberta Melo Araújo, Arlan de Assis Gonsalves, Luciano Augusto de Araújo Ribeiro, Jackson Roberto Guedes da Silva Almeida
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2aedffd6fb2c477aae9adb221150a267
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spelling	oai:doaj.org-article:2aedffd6fb2c477aae9adb221150a2672021-12-02T20:16:10ZAntinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice.1932-620310.1371/journal.pone.0258094https://doaj.org/article/2aedffd6fb2c477aae9adb221150a2672021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258094https://doaj.org/toc/1932-6203Pain 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 R1R2C = NNR3R4, 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.Maria Alice Miranda Bezerra MedeirosMariana Gama E SilvaJackson de Menezes BarbosaÉrica Martins de LavorTiago Feitosa RibeiroCícero André Ferreira MacedoLuiz Antonio Miranda de Souza Duarte-FilhoThiala Alves FeitosaJussara de Jesus SilvaHarold Hilarion FokoueCleônia Roberta Melo AraújoArlan de Assis GonsalvesLuciano Augusto de Araújo RibeiroJackson Roberto Guedes da Silva AlmeidaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0258094 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria Alice Miranda Bezerra Medeiros Mariana Gama E Silva Jackson de Menezes Barbosa Érica Martins de Lavor Tiago Feitosa Ribeiro Cícero André Ferreira Macedo Luiz Antonio Miranda de Souza Duarte-Filho Thiala Alves Feitosa Jussara de Jesus Silva Harold Hilarion Fokoue Cleônia Roberta Melo Araújo Arlan de Assis Gonsalves Luciano Augusto de Araújo Ribeiro Jackson Roberto Guedes da Silva Almeida Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice.
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 R1R2C = NNR3R4, 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	article
author	Maria Alice Miranda Bezerra Medeiros Mariana Gama E Silva Jackson de Menezes Barbosa Érica Martins de Lavor Tiago Feitosa Ribeiro Cícero André Ferreira Macedo Luiz Antonio Miranda de Souza Duarte-Filho Thiala Alves Feitosa Jussara de Jesus Silva Harold Hilarion Fokoue Cleônia Roberta Melo Araújo Arlan de Assis Gonsalves Luciano Augusto de Araújo Ribeiro Jackson Roberto Guedes da Silva Almeida
author_facet	Maria Alice Miranda Bezerra Medeiros Mariana Gama E Silva Jackson de Menezes Barbosa Érica Martins de Lavor Tiago Feitosa Ribeiro Cícero André Ferreira Macedo Luiz Antonio Miranda de Souza Duarte-Filho Thiala Alves Feitosa Jussara de Jesus Silva Harold Hilarion Fokoue Cleônia Roberta Melo Araújo Arlan de Assis Gonsalves Luciano Augusto de Araújo Ribeiro Jackson Roberto Guedes da Silva Almeida
author_sort	Maria Alice Miranda Bezerra Medeiros
title	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_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_sort	antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/2aedffd6fb2c477aae9adb221150a267
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Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice.

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