Molecular modeling of the interaction of paracetamol and 4-aminophenol with the enzymes Cyclooxygenase 1 and 2
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Abstract
In this research, a docking study of the interaction of Paracetamol and its active metabolite, 4- aminophenol, with the enzymes Cyclooxygenase 1 and Cyclooxygenase 2 is presented. The objective of this project was to use computational methods to explain, in a molecular level, the weak anti-inflammatory activity of Paracetamol by its interaction with the enzymes Cyclooxygenase 1 and 2. Quantum Mechanical methods were used for ligand optimization while Molecular Docking was used to model the interaction of these ligands with the enzymes and their active sites. Results obtained show that the poses with most affinity for Paracetamol and 4-aminophenol were not found in the active site of Cyclooxygenase 1. Comparison with arachidonic acid shows that the binding energies are about 1 kcal/mol higher indicating a weak inhibition. In the case of Cyclooxygenase 2, the results obtained were similar. This suggests that the main mechanism of action of Paracetamol is not given by the inhibition of the Cyclooxygenase 1 or 2 by this active ingredient or its primary metabolite. These results are in agreement with the differences in the pharmacological action and side effects that Paracetamol has against molecules of the same group such as Ibuprofen.
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