Syntheses and evaluation of novel isoliquiritigenin derivatives as potential dual inhibitors for amyloid-beta aggregation and 5-lipoxygenase.

A series of new isoliquiritigenin (ISL) derivatives were synthesized and evaluated as dual inhibitors for amyloid-beta (Aß) aggregation and 5-lipoxygenase (5-LO). It was found that all these synthetic compounds inhibited Aß (1-42) aggregation effectively with their IC50 values ranged from 2.2 ± 1.5 µM to 23.8 ± 2.0 µM. These derivatives also showed inhibitory activity to 5-LO with their IC50 values ranged from 6.1 ± 0.1 µM to 35.9 ± 0.3 µM. Their structure-activity relationships (SAR) and mechanisms of inhibitions were studied. This study provided potentially important information for further development of ISL derivatives as multifunctional agents for Alzheimer's disease (AD) treatment.