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New pyrazole derivative 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole: synthesis and assessment of some biological activities
Author(s) -
Oliveira Lanussy Porfiro,
Silva Daiany Priscilla Bueno,
Florentino Iziara Ferreira,
Fajemiroye James Oluwagbamigbe,
Oliveira Thiago Sardinha,
Marcelino Renato Ivan de Ávila,
Pazini Francine,
Lião Luciano Morais,
Ghedini Paulo César,
Moura Soraia Santana,
Valadares Marize Campos,
Carvalho Verônica Vale,
Vaz Boniek Gontijo,
Menegatti Ricardo,
Costa Elson Alves
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12838
Subject(s) - tetrazole , pyrazole , derivative (finance) , chemistry , combinatorial chemistry , stereochemistry , business , finance
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)‐1 H ‐pyrazol‐4‐yl]‐2 H ‐tetrazole. During the acetic acid‐induced abdominal writhing test, treatments with 5‐[1‐(4‐fluorophenyl)‐1 H ‐pyrazol‐4‐yl]‐2 H ‐tetrazole reduced abdominal writhing, while during the formalin test, 5‐[1‐(4‐fluorophenyl)‐1 H ‐pyrazol‐4‐yl]‐2 H ‐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)‐1 H ‐pyrazol‐4‐yl]‐2 H ‐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)‐1 H ‐pyrazol‐4‐yl]‐2 H ‐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)‐1 H ‐pyrazol‐4‐yl]‐2 H ‐tetrazole also blocked CaCl 2 ‐induced contraction in a dose‐dependent manner. Suggesting a safe toxicity profile, 5‐[1‐(4‐fluorophenyl)‐1 H ‐pyrazol‐4‐yl]‐2 H ‐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.