Anti-inflammatory profile of N-phenylpyrazole arylhydrazone derivatives in rats.
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.
Barja-Fidalgo
C
C
Departmento de Farmacologia, Instituto de Biologia, Universidade do Estado Rio de Janeiro, Brazil.
Fierro
I M
IM
Brando Lima
A C
AC
Teixeira Da Silva
E
E
De Amorim Câmara
C
C
Barreiro
E J
EJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006835:Hydrazones / Q000494:pharmacology*; D008297:Male; D010998:Pleurisy / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006835:Hydrazones