US EPA

6114786 

Journal Article 

Anti-inflammatory effect of a new piperazine derivative: (4-methylpiperazin-1-yl)(1-phenyl-1H-pyrazol-4-yl)methanone 

Batista, DC; Silva, DPB; Florentino, IF; Cardoso, CS; Gonçalves, MP; Valadares, MC; Lião, LM; Sanz, G; Vaz, BG; Costa, EA; Menegatti, R 

2018 

Yes 

InflammoPharmacology
ISSN: 0925-4692
EISSN: 1568-5608 

26 

1 

217-226 

English 

28825161 

10.1007/s10787-017-0390-8 

WOS:000423397700018 

AIMS: This study investigates the anti-nociceptive and anti-inflammatory effects of new piperazine compound (LQFM182) as well as the toxicity acute in vitro.

MAIN METHODS: To evaluate the anti-nociceptive activity, the acetic acid-induced abdominal writhing test, tail flick test and formalin-induced pain test were used. The anti-inflammatory activity was evaluated using the models of paw oedema and pleurisy induced by carrageenan and some inflammatory parameters were evaluated, including cell migration, myeloperoxidase enzyme activity and the levels of TNF-α and IL-1β cytokines in pleural exudate. The acute oral systemic toxicity of LQFM182 in mice was evaluated through the neutral red uptake (nru) assay.

KEY FINDINGS: LQFM182 (50, 100 or 200 mg/kg, p.o.) decreased the number of writhings induced by acetic acid in a dose-dependent manner, and an intermediate dose (100 mg/kg, p.o.) reduced the paw licking time of animals in the second phase of the formalin test. Furthermore, LQFM182 (100 mg/kg, p.o.) reduced oedema formation at all hours of the paw oedema induced by carrageenan test and in pleurisy test reduced cell migration from the reduction of polymorphonuclear cells, myeloperoxidase enzyme activity and the levels of pro-inflammatory cytokines IL-1β and TNF-α. Therefore, it was classified in GHS category 300 < LD50 < 2000 mg/kg.

SIGNIFICANCE: Reduction of the TNF-α and IL-1β levels. 

; Analgesics/pharmacology; Animals; Anti-Inflammatory Agents/pharmacology; BALB 3T3 Cells; Carrageenan/pharmacology; Cell Line; Cell Movement/drug effects; Edema/chemically induced; Edema/drug therapy; Edema/metabolism; Female; Interleukin-1beta/metabolism; Mice; Pain/drug therapy; Pain/metabolism; Pain Measurement/methods; Piperazine; Piperazines/pharmacology; Pleurisy/drug therapy; Pleurisy/metabolism; Pyrazoles/pharmacology; Tumor Necrosis Factor-alpha/metabolism; Index Medicus/