Computational study on the molecular interactions of tramadol with selected antioxidant and detoxification enzymes in Drosophila melanogaster

Olawole Yakubu  Adeniran

doi:10.30574/gscbps.2021.15.3.0147

Authors

Olawole Yakubu Adeniran Department of Biochemistry, Adekunle Ajasin University, Akungba Akoko, Ondo State, Nigeria.

DOI:

https://doi.org/10.30574/gscbps.2021.15.3.0147

Keywords:

Tramadol, Antioxidant enzyme, Molecular docking, Catalase, Cytochrome P450 2D6

Abstract

Tramadol is a potent analgesic medication prescribed worldwide for treatment of acute and chronic pains. Its relative tendency to be abused has become a public health concern. This study was designed to evaluate the molecular interactions of tramadol with selected antioxidant and detoxification enzymes of Drosophila melanogaster. The structures of CYP2D6, catalase and defense repressor 1 were retrieved from protein database (PubMed, Swiss model) while tramadol 2D structure was obtained from PubChem repository and prepared using LigPrep scripts as implemented in Small-Molecule Drug Discovery Suite of Schrödinger. 2D structure of tramadol was docked into the protein model binding site using Glide software from Schrodinger. The result revealed that, on the binding pocket of CYP2D6, tramadol and CYP2D6 inhibitor bind the protein pocket via hydrogen bond. The hydroxyl group of tramadol and the inhibitor interacts with the C=O groups of the residues Glu 128 and Lys 264 on the protein pocket respectively. Tramadol binds with higher affinity with a docking score of -4.581 kcal/mol when compared with the inhibitor which gave a docking score of -1.865 kcal/mol. With catalase, tramadol and the crystalized ligands were observed to exhibit hydrogen bonding with Ala 64 residue on the protein binding pocket with docking score of -2.348 kcal/mol and -3.431 kcal/mol respectively. The ability of tramadol to interact with these enzymes, strongly suggests that tramadol treatment may induce oxidative stress and at high dose might result in cellular toxicity. Therefore, the toxic effects of tramadol should be of concern despite the important role it plays in pain management.

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