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

ABSTRACT The current study first describes the antioxidative potential of 3‐methoxyluteolin. The experimental result is supported by computational approaches. The studied flavone (IC 50 12.40 µg/mL) was comparable to ascorbic acid in antioxidative activity against 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radicals (IC 50 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 were crucial radical scavenging sites, especially at carbon C‐4′. Kinetic evidence indicated that the reactions between the studied compound with HOO˙ radicals resulted in the k overall (overall rate constant) of 2.5 × 10 9 and 1.07 × 10 3 (M s) −1 in water and pentyl ethanoate, respectively. The studied molecule also chelated to Zn metal ion to form Zn(3‐methoxyluteolin) 2 complex with the lowest binding energy value of −322.911 kcal/mol. Considering the neurodegenerative inhibitory potentials of the studied compound, molecular docking results revealed that 3‐methoxyluteolin interacted with the active sites of both acetylcholinesterase (AChE) and butyrylcholinesterase (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.