Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice.
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 AlmeidaPublished in: PloS one (2021)
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.
Keyphrases
- anti inflammatory
- molecular docking
- oxidative stress
- inflammatory response
- drug induced
- neuropathic pain
- diabetic rats
- spinal cord injury
- molecular dynamics simulations
- chronic pain
- structure activity relationship
- mental health
- pain management
- single cell
- spinal cord
- adipose tissue
- electronic health record
- skeletal muscle
- lps induced
- insulin resistance
- endothelial cells
- respiratory failure
- stress induced
- mechanical ventilation