A Novel COX‐2 Inhibitor Pyrazole Derivative Proven Effective as an Anti‐Inflammatory and Analgesic Drug

Abstract

The introduction of new COX-2 inhibitors with high efficacy and enhanced safety profile would be a great achievement in the development of anti-inflammatory drugs. This study was designed to screen and assess the anti-inflammatory and analgesic activities as well as some of the expected side effects of some pyrazole derivatives, newly synthesized as potential COX-2 inhibitors at the Faculty of Pharmacy, Alexandria University and compared to indomethacin and celecoxib. Twelve compounds were screened for their anti-inflammatory activity using carrageenan-induced paw oedema and cotton pellet granuloma tests. On the basis of their apparent anti-inflammatory activity, four compounds with different substitutions were selected for the evaluation of their analgesic activity using the formalin-induced hyperalgesia and hot-plate tests. Compound AD 532, ((4-(3-(4-Methylphenyl)-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide)), showed very promising results. In the single-dose and subchronic toxicity studies, compound AD 532 showed no ulcerogenic effect and produced minimal effects on renal function. Furthermore, compound AD 532 was a less potent inhibitor of COX-2 in vitro than celecoxib, which may indicate lower potential cardiovascular toxicity. It is concluded that compound AD 532 appears to be a promising and safe option for the management of chronic inflammatory conditions. This study recommends more in-depth investigation into the therapeutic effects and toxicity profile of this compound including its cardiovascular toxicity.

Cheongsangbangpung-tang ameliorated the acute inflammatory response via the inhibition of NF-κB activation and MAPK phosphorylation

“…Therefore, decreases in COX-2 immunoreactivities have been used to predict the favourable effects of test materials on inflammation [32, 33]. In addition, increases in iNOS activities related to proinflammatory agents, such as endotoxin, IL-1β, TNF-α and interferon-γ, can be induced by shock and also occur following inflammatory responses in the body [34].…”

Inhibitory Effects of Traditional Herbal Formula Pyungwi-San on Inflammatory ResponseIn VitroandIn Vivo

“…Chemical mediators invoke synthesis of PGE 2 in monocytes, neutrophils, and endothelial cells at sites of inflammation; therefore, PGE 2 has been reported to a play a critical role in the inflammatory response [29]. Accordingly, decreases in the level of PGE 2 have been considered valuable in prediction of the favorable effects of test materials on inflammation [30, 31]. Results of the PGE 2 assay and Western blotting analysis of COX-2 revealed that treatment with PWS resulted in significantly inhibited induction of PGE 2 and COX-2 protein by LPS (Figures 2(a) and 3(a)), suggesting that PWS could have a therapeutic effect in treatment of pathogenic heat and pain.…”

Evaluation of anti-inflammatory, analgesic activities, and side effects of some pyrazole derivatives

“…As a consequence, researchers are seeking new molecules with comparable efficacy to known NSAIDs but with better safety profile. Mohy EL-Din et al (2010) found a new compound containing 4-(3-(4-methylphenyl)-4-cyano-1H-pyrazol-1-yl) benzenesulfonamide with good anti-inflammatory effect, no ulcerogenic effect, and minimal effect on the kidneys. Thore et al (2012) synthesized a series of novel ethyl-5-amino-3-methylthio-1H-pyrazole-4-carboxylates.…”