β‐Phenethylamine—A Phenylalanine Derivative in Brain—Contributes to Oxidative Stress by Inhibiting Mitochondrial Complexes and DT ‐Diaphorase: An In Silico Study

Summary Aim Till date, the mode of action of β‐ PEA on neurons is not well illustrated. We tested the hypothesis that β– PEA has the ability to cause oxidative stress by inhibiting the antioxidant enzyme DT ‐diaphorase and mitochondrial complexes ( C omplex‐I and complex‐ III ). Methods Using molecular docking as a tool, we here studied and compared the inhibitory capacity of β‐ PEA on DT ‐diaphorase and mitochondrial complexes. Three‐dimensional structures of mitochondrial complexes and DT ‐diaphorase and their ligands were downloaded from the respective data banks, and free energy of binding (docking scores) were determined. Results The present finding demonstrated for the first time that β‐ PEA potentiates reactive oxygen species generation by inhibiting the antioxidant enzyme DT ‐diaphorase, in addition to the mitochondrial complex‐I and complex‐ III . Conclusion As lowering of cellular antioxidant molecules is evident in many neurodegenerative disorders, β‐ PEA ‐induced lowering of DT ‐diaphorase activity may have the capability to cause neurodegeneration, which may be potentiated by its ability to inhibit mitochondrial complexes. Thus, β‐ PEA —due to its cumulative actions—may be more potent in causing neurodegeneration as compared to other endogenous neurotoxins.