Background: Several series of hydrazone derivatives of pyrazole-4-carboxaldehydes (4-
11) were designed and synthesized to screen their inflammatory activity.
Methods: The products were characterized by 1H NMR, 13C NMR and HRMS. In vitro LPS-induced
TNF-α model and in vivo xylene-induced ear-edema model were used to evaluate their antiinflammatory
Results and Conclusion: Bioassays indicated that most of the compounds markedly inhibited the
expression of TNF-α at the concentration of 10 µg/mL. Compounds 7b and 11c, two of the most
potent compounds, exhibited TNF-α inhibitory ability in a dose-dependent manner with IC50 values
of 5.56 and 3.69 µM, respectively. In vivo, intraperitoneal administration with 7b and 11c markedly
inhibited the ear edema at the doses of 20 and 50 mg/kg. Compound 11c, inhibited edema by 49.59 %
at the dose of 20 mg/kg, was comparable to the reference drug dexamethasone at the same dose (with
an inhibition of 50.49 %). To understand the binding pattern, molecular docking of representative
7b and 11c was performed, which demonstrated that both compounds have a forceful binding with
the TNF-α, and that the phenyl and hydrazide moieties of them play a significant role in binding
with the target site.