Identification of cholinesterases inhibitors from flavonoids derivatives for possible treatment of Alzheimer's disease: In silico and in vitro approaches

Nowadays, one of the methods to prevent the progress of Alzheimer's disease (AD) is to prescribe compounds that inhibit the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Researchers are actively pursuing compounds, particularly of natural origin, that exhibit enhanced efficacy and reduced side effects. The inhibition of AChE and BChE using natural flavonoids represents a promising avenue for regulating AD. This study aims to identify alternative flavonoids capable of modulating AD by down-regulating AChE and BChE activity through a molecular docking approach. Molecular docking analysis identified Ginkgetin and Kolaflavanone as potent inhibitors of AChE and BChE, respectively, among the selected flavonoids. Asn87 and Ala127 involved in the interactions of AChE-Ginkgetin complex through conventional hydrogen bonds. While in the BChE-Kolaflavanone complex, Asn83, Ser79, Gln47, and Ser287 are involved. In vitro analysis further corroborated the inhibitory potential, with Ginkgetin exhibiting an IC50 of 3.2 mM against AChE, and Kolaflavanone displaying an IC50 of 3.6 mM against BChE. These findings underscore the potential of Ginkgetin and Kolaflavanone as candidate inhibitors for the treatment of AD through the inhibition of AChE and BChE enzymes. Nevertheless, additional in vitro and in vivo studies are imperative to validate the efficacy of these compounds.