부산대학교 도서관

Objectives: Substituted hydrazine pyrazolone derivatives were evaluated for the anti-inflammatory effect, acute toxicity, and genotoxicity in this study. Materials and methods: The pyrazolone derivatives (C1-C4) were screened for in vitro albumin denaturation assay, in vitro Cyclo Oxygenase inhibition studies and in silico molecular docking studies. Compounds C3 and C4 were selected for in vivo anti-inflammatory activity assessment by carrageenaninduced paw edema model in albino rats. Compounds C3 and C4 were screened for acute toxicity studies by assessing the liver and renal function tests. Genotoxicity of C3 and C4 was determined through DNA fragmentation assay. Results and Discussion: Among the tested compounds, C3 and C4 were effective against the denaturation of egg albumin. Compounds C3 and C4 were found to be potent molecules towards significant inhibition of COX-2 but insignificant towards COX-1 inhibition. Carrageenan-induced paw edema test revealed C3 as a more potent compound than the standard drug. The result of in silico molecular docking studies of compounds with COX-1 and COX-2 enzymes correlates with the in vivo and in vitro anti-inflammatory studies. Compounds C3 and C4 were found to be nontoxic at tested dose which was evidenced by acute toxicity and DNA fragmentation studies. Conclusion: Among the tested compounds C3 has emerged as an effective non-steroidal anti-inflammatory scaffold. The potency of a compound might be attributed due to trifluoromethyl substitution. [ABSTRACT FROM AUTHOR]