title: New pyrazole derivative 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole: synthesis and assessment of some biological activities.
abstract: The molecular modification and synthesis of compounds is vital to discovering drugs with desirable pharmacological and toxicity profiles. In response to pyrazole compounds' antipyretic, analgesic, and anti-inflammatory effects, this study sought to evaluate the analgesic, anti-inflammatory, and vasorelaxant effects, as well as the mechanisms of action, of a new pyrazole derivative, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole. During the acetic acid-induced abdominal writhing test, treatments with 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced abdominal writhing, while during the formalin test, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced licking times in response to both neurogenic pain and inflammatory pain, all without demonstrating any antinociceptive effects, as revealed during the tail flick test. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also reduced carrageenan-induced paw edema and cell migration during the carrageenan-induced pleurisy test. As demonstrated by the model of the isolated organ, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole exhibits a vasorelaxant effect attenuated by Nω-nitro-l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, tetraethylammonium or glibenclamide. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also blocked CaCl2-induced contraction in a dose-dependent manner. Suggesting a safe toxicity profile, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced the viability of 3T3 cells at higher concentrations and was orally tolerated, despite signs of toxicity in doses of 2000 mg/kg. Lastly, the compounds' analgesic activity might be attributed to the involvement of the NO/cGMP pathway and K+channels observed in the vasorelaxant effect.
authors.affiliation: Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Lanussy Porfiro
authors.initials: LP
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Daiany Priscilla Bueno
authors.initials: DP
authors.lastname: da Silva
authors.affiliation: Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Iziara Ferreira
authors.initials: IF
authors.lastname: Florentino
authors.affiliation: Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: James Oluwagbamigbe
authors.initials: JO
authors.lastname: Fajemiroye
authors.affiliation: Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Thiago Sardinha
authors.initials: TS
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Cellular Pharmacology and Toxicology, FarmaTec, College of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Renato Ivan de Ávila
authors.initials: RI
authors.lastname: Marcelino
authors.affiliation: Laboratory of Medicinal Pharmaceutical Chemistry, College of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Francine
authors.initials: F
authors.lastname: Pazini
authors.affiliation: Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Luciano Morais
authors.initials: LM
authors.lastname: Lião
authors.affiliation: Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Paulo César
authors.initials: PC
authors.lastname: Ghedini
authors.affiliation: Laboratory of Cellular Pharmacology and Toxicology, FarmaTec, College of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Soraia Santana
authors.initials: SS
authors.lastname: de Moura
authors.affiliation: Laboratory of Cellular Pharmacology and Toxicology, FarmaTec, College of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Marize Campos
authors.initials: MC
authors.lastname: Valadares
authors.affiliation: Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Verônica Vale
authors.initials: VV
authors.lastname: de Carvalho
authors.affiliation: Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Boniek Gontijo
authors.initials: BG
authors.lastname: Vaz
authors.affiliation: Laboratory of Medicinal Pharmaceutical Chemistry, College of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Menegatti
authors.affiliation: Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Elson Alves
authors.initials: EA
authors.lastname: Costa
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D058633:Antipyretics / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D058633:Antipyretics; D011720:Pyrazoles
keywords: NO/cGMP pathway; anti-inflammatory effect; antinociceptive effect; pyrazole derivatives; vasorelaxant effect