1. Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice.
- Author
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Medeiros MAMB, Gama E Silva M, de Menezes Barbosa J, Martins de Lavor É, Ribeiro TF, Macedo CAF, de Souza Duarte-Filho LAM, Feitosa TA, de Jesus Silva J, Fokoue HH, Araújo CRM, de Assis Gonsalves A, Augusto de Araújo Ribeiro L, and Almeida JRGDS
- Subjects
- Analgesics chemistry, Analgesics therapeutic use, Animals, Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents therapeutic use, Artemia drug effects, Carrageenan, Edema chemically induced, Edema drug therapy, Hydrazones chemical synthesis, Hydrazones chemistry, Hydrazones therapeutic use, Male, Mice, Molecular Docking Simulation, Toxicity Tests, Analgesics pharmacology, Anti-Inflammatory Agents pharmacology, Hydrazones pharmacology
- Abstract
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., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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