Interaction of Paracetamol, Propyphenazone and Their Complexes With Cyclooxygenase Isoforms: A Molecular Docking Approach

The paracetamol–propyphenazone combination is one of the classic analgesic formulations used for the treatment of acute pain of mild to moderate intensity. By combining the antipyretic and analgesic properties of paracetamol with the rapid analgesic and anti-inflammatory effects of propyphenazone, this association provides an enhanced therapeutic response, characterized by a fast onset of action and effective symptom relief. It is frequently used in the management of tension-type headaches, migraines, and other forms of acute pain, being appreciated for its relatively favorable tolerability profile. The main objective of this study is to determine whether the interactions between paracetamol, propyphenazone, and cyclooxygenase enzymes are influenced by the combination of these two drugs. This was achieved using the HEX 8.0 docking program. Binding energy was used as a measure to assess the strength of the interactions. Our analysis shows that the strongest interaction with COX-2 was observed for the propyphenazone–paracetamol complex, indicating that when propyphenazone is assigned as the receptor and paracetamol as the ligand, the resulting complex achieves optimal accommodation within the COX-2 active site. These findings highlight the importance of understanding drug–drug interactions. Therefore, a solid comprehension of these dynamics is essential to ensure the efficacy of therapeutic combinations.