An In Silico Evaluation Of The Multifunctional Activity Of Crocetin Against Neurodegenerative Disease

The multifunctional activity of crocetin originating from saffron flowers against neurodegenerative disease, was investigated using DFT and molecular docking simulations. The $\mathrm{HOO}^{\bullet}$ free radical trapping activity of crocetin is faster than that of Trolox in polar and nonpolar environments. The RAF reaction is the main process responsible for the antiradical activity of crocetin in nonpolar environments. On the other hand, in polar environments, the SET pathway is preferred. Among the complexes examined, the Cu(II) complex with the dianion ligand that forms at sites 1 and 1-2 has the greatest stability. This finding suggests that the dianionic form of crocetin exhibits more affinity for binding to Cu(II) ions, hence reducing the amount of free $\mathbf{C u}$ (II) ions associated with neurodegenerative diseases. Furthermore, the molecular docking simulations indicate that crocetin exhibits a strong binding affinity with enzymes AChE, BChE, and MAO-B, surpassing the activity of the commercial drugs.