In this study, Wedelolactone's multitarget activity against Alzheimer's disease was examined using density functional theory and molecular docking techniques. At physiological pH, the pK a and molar fractions have been estimated. The most likely relative rate constants of two radical scavenger mechanisms are formal hydrogen transfer in a lipid environment and single-electron transfer in a water solvent. Compared to Trolox (k overall = 8.96 × 104 M-1 s-1), Wedelolactone (k overall = 4.26 × 109 M-1 s-1) is more efficient in scavenging the HOO• radical in an aqueous environment. The chelation capacity of metals was investigated by examining the complexation of the Cu(II) ion at various coordination positions and calculating the complexation kinetic constants. Furthermore, molecular docking simulations showed that the known forms of Wedelolactone at physiological pH effectively inhibited the AChE and BChE enzymes by comparing their activity to that of tacrine (control). Wedelolactone is a promising drug candidate for Alzheimer's disease therapy in light of these findings.
© 2023 The Authors. Published by American Chemical Society.