Abstract
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.
Highlights
Inflammation is considered as a part of our body’s defense mechanisms against invasive organisms
We evaluated a series of substituted pyrazole derivatives with a structural likeness to celecoxib, a pyrazole-based anti-inflammatory agent (Figure 1) as inhibitors of LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) productions
The final compounds 1a–m were synthesized via the pathway demonstrated in Scheme 1. 2-Chloro-5-methylphenol (2) was reacted with dimethyl sulfate/potassium carbonate to obtain methoxy derivative
Summary
Inflammation is considered as a part of our body’s defense mechanisms against invasive organisms. Limiting PGE2 production via inhibition of COX-2 protein expression and/or enzymatic activity is another useful approach for the treatment of inflammation. Nitric oxide (NO) has another considerable contribution to inflammation development ( it could produce anti-inflammatory effect under other normal physiological conditions) [9,10,11].
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