In Vivo and In Silico Molecular Modeling Studies of Newly Synthesized Pyrazoles for Their Anti-Inflammatory and Analgesic Properties

Abstract

Background: Pyrazole derivatives have gained attention as potential leads for developing anti-inflammatory and analgesic drugs. Chemical modifications of pyrazole structures offer a strategy to enhance their therapeutic properties, while minimizing undesirable effects. Objective: This study aimed to synthesize novel pyrazole derivatives through chemical modifications and assess their anti-inflammatory and analgesic activities. Methods: A series of pyrazole variants were synthesized by reacting various acetophenone derivatives and diethyl oxalate in basic conditions, followed by treatment with glacial acetic acid and hydrazine hydrate. The resulting compounds were further methylated and acetylated. The synthesized compounds were characterized using elemental analysis, 1H NMR, IR, and MASS spectroscopy. The anti-inflammatory activity was evaluated using the rat paw edema technique induced by carrageenan, while the analgesic activity was assessed using the writhing reflux method. Results: Among the newly synthesized pyrazole derivatives, compounds 3b, 3e and 3g′ demonstrated significant anti-inflammatory activity with reduced ulcerogenic potential. Compounds 3d, 3b′ and 3d′ exhibited notable analgesic activity compared to the standard drug. The chemical modifications introduced in these derivatives were confirmed through spectroscopic analyses. Conclusion: The findings of this study highlight the potential of pyrazole derivatives as promising candidates for anti-inflammatory and analgesic drug development. The structural modifications performed in this research improved the therapeutic activities of the compounds, while addressing safety concerns. Further investigations are warranted to elucidate the underlying mechanisms of action and optimize the pharmacological profiles of these novel pyrazole derivatives.