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

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• 作者：Lanussy Porfiro de Oliveira ; Daiany Priscilla Bueno da Silva ; Iziara Ferreira Florentino ; James Oluwagbamigbe Fajemiroye ; Thiago Sardinha de Oliveira ; Renato Ivan de Á ; vila Marcelino ; Francine Pazini ; Luciano Morais Li&atilde ; o ; Paulo Cé ; sar Ghedini ; Soraia Santana de Moura ; Marize Campos Valadares ; Verô ; nica Vale de Carvalho ; Boniek Gontijo Vaz ; Ricardo Menegatti and Elson Alves Costa
• 刊名：Chemical Biology & Drug Design
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：89
• 期：1
• 页码：124-135
• 全文大小：1225K
• ISSN：1747-0285

文摘

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.