Anti-inflammatory profile of N-phenylpyrazole arylhydrazone derivatives in rats.
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| Abstract |
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 investigated for anti-inflammatory activity in the carrageenan-induced pleurisy model in rats. The compounds have different oxygenated substituent groups in the aryl group of the hydrazone framework to ensure a different range of redox properties. A new arylhydrazone derivative, 2,6-di-tert-butyl-4-(4-nitro-3-methyl-N-phenylpyrazol-5-yl-hydr azonomethyl)phenol, was also synthesized and tested for anti-inflammatory activity. Although all the compounds significantly inhibited (by 30-90%) neutrophil accumulation in the pleural cavity, there was great variability in the anti-oedematogenic effect of the compounds (3-96%). 5-(4'-Hydroxy-3'-methoxybenzylidene)hydrazone-3-methyl-4-nitrop henylpyrazole was the most active compound in this series; it had a remarkable antiinflammatory profile, almost blocking both assays. In contrast, the compound with a 2,6-di-tert-butylated hydroxybenzene ring on the hydrazone group inhibited neutrophil migration only. These results will be useful for further structure-activity relationship studies devoted to improving the dual prostaglandin synthase-5-lipoxygenase activity of these derivatives and determining the minimum structural requirements necessary for this activity.
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| Authors | C Barja-Fidalgo, I M Fierro, A C Brando Lima, E Teixeira Da Silva, C De Amorim Câmara, E J Barreiro |
| Journal | The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 51 Issue 6 Pg. 703-7 (Jun 1999) ISSN: 0022-3573 [Print] England |
| PMID | 10454047 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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