Exploring the Multitarget Activity of Wedelolactone against Alzheimer?s Disease: Insights from In Silico Study

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 pKa 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 (koverall = 8.96 x 104 M-1 s-1), Wedelolactone (koverall = 4.26 x 109 M-1 s-1) is more efficient in scavenging the HOO center dot radical in an aqueous environ-ment. 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.

Automated summary

In this study, the multitarget activity of Wedelolactone against Alzheimer's disease was investigated using density functional theory and molecular docking techniques. The scavenging efficiency of Wedelolactone for the HOO· radical in an aqueous environment was found to be higher than Trolox. The chelation capacity of metals and the inhibitory effect of Wedelolactone on AChE and BChE enzymes were also examined.