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

•A series of novel isoliquiritigenin (ISL) derivatives were synthesized.•Most of synthesized compounds had better inhibition on Aβ aggregation and 5-LO.•The amide derivatives (4b–d) exhibit strong inhibitory potency against both targets.

A series of new isoliquiritigenin (ISL) derivatives were synthesized and evaluated as dual inhibitors for amyloid-beta (Aβ) aggregation and 5-lipoxygenase (5-LO). It was found that all these synthetic compounds inhibited Aβ (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.

Graphical abstractA series of new isoliquiritigenin derivatives were synthesized and evaluated as a dual inhibitor of Aβ self-induced aggregation and 5-lipoxygenase (5-LO). Compound 4d exhibited strong inhibitory potency against both targets.Figure optionsDownload full-size imageDownload as PowerPoint slide