Evaluation of the inhibitory effects of pyridylpyrazole derivatives on lps-induced pge₂ productions and nitric oxide in murine raw 264.7 macrophages

A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E₂ (PGE₂ ) and nitric oxide (NO) production in RAW 264.7 macrophages. The target compounds 1a–m have first been assessed for cytotoxicity against RAW 264.7 macrophages to determine their non-cytotoxic concentration(s) for anti-inflammatory testing to make sure that the inhibition of PGE₂ and NO production would not be caused by cytotoxicity. It was found that compounds 1f and 1m were the most potent PGE₂ inhibitors with IC₅₀ values of 7.1 and 1.1 µM, respectively. In addition, these compounds also showed inhibitory effects of 11.6% and 37.19% on LPS-induced NO production, respectively. The western blots analysis of COX-2 and iNOS showed that the PGE₂ and NO inhibitory effect of compound 1m are attributed to inhibition of COX-2 and iNOS protein expression through inactivation of p38.