Anti-inflammatory profile of N-phenylpyrazole arylhydrazone derivatives inrats

A series of synthetic N-phenylpyrazole arylhydrazone compounds, rationally designed as mixed-hybrid isosteres of two known inhibitors of prostaglandin synthase and 5-lipoxygenase enzymes, BW-755c and CBS-1108, has been invest igated for anti-inflammatory activity in the carrageenan-induced pleurisy m odel in rats. The compounds have different oxygenated substituent groups in the aryl group of the hydrazone framework to ensure a different range of r edox properties. A new arylhydrazone derivative, 2,6-di-tert-butyl-4-(4-nit ro-3-methyl-N-phenylpyrazol-5-yl-hydrazonomethyl)phenol, was also synthesiz ed and tested for anti-inflammatory activity. Although all the compounds significantly inhibited (by 30-90%) neutrophil a ccumulation in the pleural cavity, there was great variability in the anti- oedematogenic effect of the compounds (3-96%). 5-(4'-Hydroxy-3'-methoxybenz ylidene)hydrazone-3-methyl-4-nitrophenylpyrazole was the most active compou nd in this series; it had a remarkable antiinflammatory profile, almost blo cking both assays. In contrast, the compound with a 2,6-di-tert-butylated h ydroxybenzene ring on the hydrazone group inhibited neutrophil migration on ly. These results will be useful for further structure-activity relationship st udies devoted to improving the dual prostaglandin synthase-5-lipoxygenase a ctivity of these derivatives and determining the minimum structural require ments necessary for this activity.