Affiliations: [a] Department of Pharmacy, Abdul Wali khan University Mardan, Pakistan
| [b] Department of Pharmacy, University of Malakand, Chakdara, Dir, Pakistan
| [c] Department of Chemistry, Faculty of Science, Taif University, Taif 21974, Saudi Arabia
| [d] Department of Biochemistry, Abdul Wali khan University Mardan, Pakistan
Correspondence:
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Corresponding author: Prof. Dr. Haroon Khan, Department of Pharmacy, Abdul Wali khan University Mardan, 23200, Pakistan. E-mails: [email protected] and [email protected].
Abstract: In this study, the anti-nociceptive potential of Schiff bases derivatives of 4-aminoantioyrine, (Z)-4-(4-hydroxy-3-methoxybenzylideneamino)-2, 3-dimethyl-1-phenyl-1, 2dihydropyrazol-5-one 1 and (Z)-4-(2-nitrobenzylideneamino)-2, 3-dimethyl-1-phenyl-1-2-dihydropyrazol-5-one 2 were tested in various mice pain models and their binding affinities with different drug targets were evaluated through molecular docking studies. The binding scores were calculated through molecular docking techniques for receptor sensitivity. Acute toxicity test suggests the safety of both compounds up 200 mg/kg. In the righting test, compound 1 and 2 had a significant effect in a dose-dependent manner and showed 59.46% and 48.40% blockade of pain at 150 mg/kg, respectively. In the formalin test, dose-dependently compound 1 showed 52.95% and 62.02% of inhibition in the early and late phase at 150 mg/kg. Similarly, Compound 2 showed 45.74% and 55.95% inhibition in the early and late phases at 150 mg/kg, respectively. In the tail immersion test, both compounds caused significant pain inhibition during various assessment times with maximum effects at 74.94% and 66.80% for 1 and 2 respectively at 150 mg/kg after 120 min. In molecular docking studies, compounds 1 and 2 showed a greater affinity for LOX with a docking score of –6.50 and 6.57 respectively. Similarly, for compounds 1 and 2 the docking was –4.94 and –4.83 with COX-1 while –5.10 and –4.85 with COX-2, respectively. Taken together, both the compounds exhibited marked antinociceptive effects in various pain-induced models possibly mediated by inhibition of LOX and COX pathways.
