Synthesis, Pharmacological Evaluation, and Molecular Docking Studies of Novel Ibuprofen Amide Derivatives Containing Substituted 2-Aminothiophenes
摘要
Various novel ibuprofen amide derivatives from substituted 2-aminothiophenes (I1–I12) were designed and synthesized using appropriate procedures. Physical and spectral data were used to characterize every molecule that was synthesized. In comparison with the standard drugs, the in vitro anti-oxidant and the in vitro and in-vivo anti-inflammatory activities of the compounds were assessed. When compared with the standard ascorbic acid, the majority of the compounds showed good anti-oxidant activity. The synthesized compounds were tested for in vitro anti-inflammatory activity by protein denaturation and human red-blood cells mem-brane stabilization methods. Among them, the compounds I3, I5, and I6 showed significant in vitro anti-in-flammatory activity. Further, the synthesized compounds were tested for in vivo anti-inflammatory activity by the carrageenan rat paw edema method. The results of in vivo studies indicated that compounds I5 and I11 possess significant anti-inflammatory activity compared with the standard drug ibuprofen. To rationalize the pharmacological results, the binding mode of the title compounds (I1–I12) was investigated using the AutoDock 1.5.7 docking program using COX-2 enzyme (PDBID: 4PH9). The docking results revealed that the I5 compound showed the highest binding energy of –9.0 kcal/mol.