A novel COX-2 inhibitor pyrazole derivative proven effective as an anti-inflammatory and analgesic drug.
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.
Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt.
Mahmoud M
MM
Mohy El-Din
Amira M
AM
Senbel
Azza A
AA
Bistawroos
Ahmed
A
El-Mallah
Nour A
NA
Nour El-Din
Adnan A
AA
Bekhit
Heba A
HA
Abd El Razik
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002351:Carrageenan / Q000633:toxicity; D000068579:Celecoxib; D002908:Chronic Disease; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced; D005260:Female; D005557:Formaldehyde / Q000633:toxicity; D006930:Hyperalgesia / Q000139:chemically induced; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000628:therapy*; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D014456:Ulcer / Q000139:chemically induced / Q000473:pathology; D000096926:Benzenesulfonamides
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D002351:Carrageenan; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors; D005557:Formaldehyde; D007213:Indomethacin; D011720:Pyrazoles; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C559141:4-(3-(4-methylphenyl)-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide; C031280:pyrazole