Abstract
Advances have been made in the search for new multi-target modulators to control pain and inflammation. Therefore, compound 3,5-di-tert-butyl-4-hydroxyphenyl)(4-methylpiperazin-1-yl)methanone (LQFM202) was synthesised and evaluated. First, in vitro assays were performed for COX-1, COX-2, and 5-LOX enzymes. Subsequently, adult female Swiss albino mice treated orally with LQFM202 at doses of 25–200 mg/kg were subjected to acetic acid-induced writhing, formalin-induced pain, carrageenan-induced hyperalgesia, carrageenan- or zymosan-induced paw oedema, or pleurisy. LQFM202 inhibited COX-1, COX-2, and LOX-5 (IC50 = 3499 µM, 1565 µM, and 1343 µM, respectively). In acute animal models, LQFM202 (50, 100, or 200 mg/kg) decreased the amount of abdominal writhing (29%, 52% and 48%, respectively). Pain in the second phase of the formalin test was reduced by 46% with intermediate dose. LQFM202 (100 mg/kg) reduced the difference in nociceptive threshold in all 4 h evaluated (46%, 37%, 30%, and 26%, respectively). LQFM202 (50 mg/kg) decreased the carrageenan-oedema from the second hour (27%, 31% and 25%, respectively); however, LQFM202 (100 mg/kg) decreased the carrageenan-oedema in all hours evaluated (35%, 42%, 48% and 50%, respectively). When using zymosan, LQFM202 (50 mg/kg) decreased the oedema in all hours evaluated (33%, 32%, 31% and 20%, respectively). In the carrageenan-pleurisy test, LQFM202 (50 mg/kg) reduced significantly the number of polymorphonuclear cells (34%), the myeloperoxidase activity (53%), TNF-α levels (47%), and IL-1β levels (58.8%). When using zymosan, LQFM202 (50 mg/kg) reduced the number of polymorphonuclear and mononuclear cells (54% and 79%, respectively); and the myeloperoxidase activity (46%). These results suggest antinociceptive and anti-inflammatory effects of LQFM202.
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The authors are grateful to CAPES and CNPq for financial support.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), nº 88882.385883/2019-1. Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), nº 306530/2020-1.
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ANM, EAC and DPBS conceived the study, designed the pharmacological assays, and drafted the manuscript. DSA, IFF, LKSM, LCT, JLRM and JOF carried out the pharmacological assays in vivo and in vitro. DCB, LSM, BGV, LML, GARO and RM carried out the all stages of design and synthesis of compound LQFM 202. All the authors critically revised the manuscript for important intellectual content and approved its final version.
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Martins, A.N., de Souza Almeida, D., Florentino, I.F. et al. Pharmacological evaluation of antinociceptive and anti-inflammatory activities of LQFM202: a new piperazine derivative. Inflammopharmacol 31, 411–422 (2023). https://doi.org/10.1007/s10787-022-01103-x
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DOI: https://doi.org/10.1007/s10787-022-01103-x