Molecular docking and two-dimensional quantitative structure-activity relationship studies of synthetic flavonoids on...

For the first time, the enzymatic inhibition activity of 13 synthetic flavonoids was assessed by quantitative structure-activity relationship (QSAR) modeling and molecular docking with the three states of the enzyme horseradish peroxidase (HRP). The results show that apigenin, quercetin, kaempferol, fisetin, tricetin, and luteolin exerted a high competitive inhibition on HRP (Ki between 0.14 and 1.74 mM) compared with other flavonoids. The QSAR model of enzymatic activity (R²  = 0.95, RMSE = 5.48) showed that Ghose-Crippen octanol-water partition coefficient (Alog P) and lowest unoccupied molecular orbital's energy (ε_lumo ) correlated with 0.65 and 0.17, respectively, with Ki values. According to the docking results using Molegro Virtual Docker program, all the flavonoids have shown great binding affinity towards peroxidase. Apigenin has the largest MolDock score in the three states of HRP noting an increased affinity of these flavonoids between compound I and compound II by 2.26%. However, these affinities strongly decrease between compound II and compound III by 28.43% especially for luteolin whose MolDock score decreased by 74.7%. With the results of docking, the affinities of the flavonoids tested and translated by their Ki values are much more presentative of the inhibition of the first reaction states of HRP because their inhibitory effect is important.