Antioxidative Potential of 3-methoxyluteolin: Density Functional Theory (DFT), and Molecular Docking and Dynamics - A Combined Experimental and Computational Study

The flavone 3-methoxyluteolin (IC50 12.40 µg/mL) was comparable ascorbic acid in antioxidative activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (IC50 11.38 µg/mL). From DFT (density functional theory) calculations, its principal radical mechanism in gas and lipid was the FHT (formal hydrogen transfer), whereas the SPL-ET (sequential proton loss-electron transfer) was the main way in water. Hydroxyl groups, especially at carbon C-4', were the crucial radical scavenging sites. Kinetic evidence indicated that the reactions between the studied compound with HOO˙ radicals resulted in the koverall (overall rate constant) of 2.5 x 109 and 1.07 x 103 M-1 s-1 in water and pentyl ethanoate, respectively. The studied molecule chelated to Zn metal ion to form Zn(3-methoxyluteolin)2 complex with the lowest binding energy value of -322.911 kcal/mol. Considering neurodegenerative inhibitory potentials of the studied compound, molecular docking results revealed that 3-methoxyluteolin interacted with the active sites of both acetylcholinesterase (AChE) and butyrylcholinestease (BChE) with the binding affinities of -9.493 and -8.812 kcal/mol, respectively, which are stronger than the reference compound tacrine. To assess the structural stability and binding interactions with each studied protein, molecular dynamics simulations were conducted. The results indicated that the 3-methoxyluteolin complexes with AChE and BChE remained stable during a simulation period.