New pyrazole derivative 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole: synthesis and assessment of some biological activities.

Autor: de Oliveira LP; Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., da Silva DP; Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Florentino IF; Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Fajemiroye JO; Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., de Oliveira TS; Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Marcelino RI; Laboratory of Cellular Pharmacology and Toxicology, FarmaTec, College of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil., Pazini F; Laboratory of Medicinal Pharmaceutical Chemistry, College of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil., Lião LM; Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil., Ghedini PC; Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., de Moura SS; Laboratory of Cellular Pharmacology and Toxicology, FarmaTec, College of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil., Valadares MC; Laboratory of Cellular Pharmacology and Toxicology, FarmaTec, College of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil., de Carvalho VV; Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil., Vaz BG; Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil., Menegatti R; Laboratory of Medicinal Pharmaceutical Chemistry, College of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil., Costa EA; Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
Jazyk: angličtina
Zdroj: Chemical biology & drug design [Chem Biol Drug Des] 2017 Jan; Vol. 89 (1), pp. 124-135. Date of Electronic Publication: 2016 Sep 14.
DOI: 10.1111/cbdd.12838
Abstrakt: 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 CaCl 2 -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.
(© 2016 John Wiley & Sons A/S.)
Databáze: MEDLINE
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