Anti-inflammatory, antinociceptive, and vasorelaxant effects of a new pyrazole compound 5-(1-(2-fluorophenyl)-1H-pyrazol-4-yl)-1H-tetrazole: role of NO/cGMP pathway and calcium channels

Oliveira, Lanussy Porfiro de; Florentino, Iziara Ferreira; Silva, Daiany Priscilla Bueno da; Pazini, Francine; Carvalho, Flávio Silva de; Sanz Lobón, Germán; Vaz, Boniek Gontijo; Rocha, Fabio Fagundes da; Fajemiroye, James Oluwagbamigbe; Ghedini, Paulo César; Liao, Luciano Morais; Menegatti, Ricardo; Costa, Elson Alves; Oliveira, Thiago Sardinha de

Anti-inflammatory, antinociceptive, and vasorelaxant effects of a new pyrazole compound 5-(1-(2-fluorophenyl)-1H-pyrazol-4-yl)-1H-tetrazole: role of NO/cGMP pathway and calcium channels

Data

2023

Autores

Oliveira, Lanussy Porfiro de

Florentino, Iziara Ferreira

Silva, Daiany Priscilla Bueno da

Pazini, Francine

Carvalho, Flávio Silva de

Sanz Lobón, Germán

Vaz, Boniek Gontijo

Rocha, Fabio Fagundes da

Fajemiroye, James Oluwagbamigbe

Ghedini, Paulo César

Resumo

Molecular modification of compounds remains important strategy towards the discovery of new drugs. In this sense, this study presents a new pyrazole derivative 5-(1-(2-fluorophenyl)-1H-pyrazol-4-yl)-1H-tetrazole (LQFM039) and evaluated the anti-inflammatory, analgesic, and vasorelaxant effects of this compound as well the mechanisms of action involved in the pharmacological effects. For this, mice were orally treated with LQFM039 (17.5, 35, or 70 mg/kg) prior acetic acid-induced abdominal writhing, formalin, tail flick, and carrageenan-induced paw edema protocols. In addition, vascular reactivity protocols were made with aortic rings contraction with phenylephrine and stimulated with graded concentrations of LQFM039. Abdominal writhing and licking time in both neurogenic and inflammatory phases of formalin were reduced with LQFM039 without altering latency to nociceptive response in the tail flick test. Carrageenan-induced paw edema showed that LQFM039 reduces edema and cell migration. In addition, the mechanism of action of LQFM039 involves NO/cGMP pathway and calcium channels, since this new pyrazole derivate elicited concentration-dependent relaxation attenuated by Nω-nitro-l-arginine methyl ester and 1H-[1,2,4] oxadiazolo [4,3-alpha]quinoxalin-1-one, and blockade of CaCl2-induced contraction. Altogether, our finding suggests anti-inflammatory, antinociceptive, and vasorelaxant effect of this new pyrazole derivative with involvement of NO/cGMP pathway and calcium channels.

Citação

OLIVEIRA, Lanussy P. de et al. Anti-inflammatory, antinociceptive, and vasorelaxant effects of a new pyrazole compound 5-(1-(2-fluorophenyl)-1 H -pyrazol-4-yl)-1 H -tetrazole: role of NO/cGMP pathway and calcium channels. Canadian Journal of Physiology and Pharmacology, Ottawa, v. 101, n. 5, p. 216-225, 2023. DOI: 10.1139/cjpp-2022-0428. Disponível em: https://cdnsciencepub.com/doi/10.1139/cjpp-2022-0428. Acesso em: 28 jun. 2023.