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.

A 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 as PowerPoint slide