Investigation of the anti-inflammatory and analgesic activities of promising pyrazole derivative

被引:58
作者
Bekhit, Adnan A. [1 ,2 ]
Nasralla, Sherry N. [2 ]
El-Agroudy, Eman J. [1 ]
Hamouda, Nahla [3 ]
Abd El-Fattah, Ahmed [4 ,5 ]
Bekhit, Salma A. [6 ]
Amagase, Kikuko [7 ]
Ibrahim, Tamer M. [8 ]
机构
[1] Alexandria Univ, Fac Pharm, Dept Pharmaceut Chem, Alexandria 21521, Egypt
[2] Univ Bahrain, Coll Hlth & Sport Sci, Allied Hlth Dept, Pharm Program,Pharmacol Stream, Zallaq, Bahrain
[3] Alexandria Univ, Fac Med, Dept Clin Pharmacol, Alexandria, Egypt
[4] Alexandria Univ, Inst Grad Studies & Res, Dept Mat Sci, Alexandria 21526, Egypt
[5] Univ Bahrain, Coll Sci, Dept Chem, POB 32038, Sakhir, Bahrain
[6] Alexandria Univ, High Inst Publ Hlth, Alexandria 21568, Egypt
[7] Ritsumeikan Univ, Coll Pharmaceut Sci, Lab Pharmacol & Pharmacotherapeut, Kusatsu, Shiga, Japan
[8] Kafrelsheikh Univ, Fac Pharm, Dept Pharmaceut Chem, Kafrelsheikh 33516, Egypt
关键词
Pyrazole derivative; COX-2; inhibitors; Analgesic effect; Anti-inflammatory activity; docking; MD; FORMALIN TEST; BIOLOGICAL EVALUATION; MOLECULAR-DYNAMICS; ANIMAL-MODELS; CELECOXIB; DRUGS; PHARMACOLOGY; INHIBITORS; PAIN; INFLAMMATION;
D O I
10.1016/j.ejps.2021.106080
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The development of new COX-2 inhibitors with analgesic and anti-inflammatory efficacy as well as minimal gastrointestinal, renal and cardiovascular toxicity, is of vital importance to patients suffering from chronic course pain and inflammatory conditions. This study aims at evaluating the therapeutic activity and adverse drug reactions associated with the use of the newly synthesized pyrazole derivative, compound AD732, E-4-[3-(4-methylphenyl)-5-hydroxyliminomethyl-1H-pyrazol-1-yl]benzenesulfonamide, as compared to indomethacin and celecoxib as standard agents. Anti-inflammatory activity was assessed using carrageenan-induced rat paw edema and cotton pellet granuloma tests; formalin-induced hyperalgesia and hot plate tests were done to study analgesic activity. In vitro tests to determine COX-1/COX-2 selectivity and assessment of renal and gastric toxicity upon acute exposure to AD732 were also conducted. Compound AD732 exhibited promising results; higher antiinflammatory and analgesic effects compared to standard agents, coupled with the absence of ulcerogenic effects and minimal detrimental effects on renal function. Additionally, compound AD732 was a less potent inhibitor of COX-2 in vitro than celecoxib, which may indicate lower potential cardiovascular toxicity. It may be concluded that compound AD732 appears to be a safer and more effective molecule with promising potential for the management of pain and inflammation.
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页数:10
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