Evaluation of Analgesic, Anti-Inflammatory, Antioxidant, Toxicity, Molecular Docking, and ADMET Analysis of Ibuprofen Derivatives

Ibuprofen analogues were developed and examined for biological activity in this study. The Schotten–Baumann method produces four ibuprofen derivatives: P-1 [phenyl-2-(4-isobutylphenyl) propanoate], P-2 [4-aminophenyl-2-], P-3 [4-chlorophenyl-2-], and P-4 [4-nitrophenyl-2-]. An analgesic hot plate investigation found that the test dose of derivatives and ibuprofen delayed the reaction time from 30 to 150 min for ibuprofen, P-1, P-2, and P-3, resulting in good central analgesic efficacy. The acetic acid-induced writhing test also exhibits significant activity as inhibition of the number of writhing by P-1 (93.41%), P-2 (65.26%), P-3 (83.23%), P-4 (96.40%), and ibuprofen (87.42%). In vitro anti-inflammatory studies indicated dose-dependent protein denaturation inhibition. The carrageenan-induced paw edema shows that P-1, P-2, and P-3 have good anti-inflammatory properties. The derivative toxicity analysis showed no significant difference compared to ibuprofen and the control. The derivatives were found to be moderate antioxidants, and the cytotoxicity investigation of ibuprofen derivatives showed that P-1 is more cytotoxic than the others. In molecular docking tests, the synthesized derivatives P-2 have the highest binding affinity (−8.8 Kcal/mol) in cyclooxygenase (COX)-1, and P-2 (−8.2 Kcal/mol) have a higher binding affinity compared to ibuprofen in COX-2, suggesting more selectivity. ADMET studies showed significantly higher protein binding affinity, less toxicity, and increased absorption by increasing lipophilicity of the analogues.