Design, synthesis, and cholinesterase inhibition assay of liquiritigenin derivatives as anti-Alzheimer's activity

The marine environment is a rich resource for discovering functional materials, and seaweed is recognized for its potential use in biology and medicine. Liquiritigenin has been isolated and identified from Sargassum pallidum. To find new anti-Alzheimer's activity, we designed and synthesized thirty-two 7-prenyloxy-2,3-dihydroflavanone derivatives (3a-3p) and 5-hydroxy-7-prenyloxy-2,3-dihydro-flavanone derivatives (4a-4p) as cholinesterases inhibitors based on liquiritigenin as the lead compound. Inhibition screening against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) indicated that all synthesized compounds possessed potent AChE inhibitory activity and moderated to weak BuChE inhibitory activity in vitro. Kinetic studies demonstrated that compound 4o inhibited AChE via a dual binding site ability. In addition, all compounds displayed the radical scavenging effects. Finally, the molecular docking simulation of 4o in AChE active site displayed good agreement with the obtained the pharmacological results.

Automated summary

The marine environment is a rich source of functional materials, with seaweed containing potential compounds like liquiritigenin. In this study, derivatives based on liquiritigenin were synthesized and tested for their inhibitory effects on cholinesterases, showing potency against acetylcholinesterase and moderate to weak activity against butyrylcholinesterase. Kinetic studies revealed a dual binding site inhibition mechanism for compound 4o against AChE, and all tested compounds also displayed radical scavenging effects. The molecular docking simulation of 4o in the AChE active site correlated well with the pharmacological results.