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 (A beta) aggregation and 5-lipoxygenase (5-LO). It was found that all these synthetic compounds inhibited A beta (1-42) aggregation effectively with their IC50 values ranged from 2.2 +/- 1.5 mu M to 23.8 +/- 2.0 mu M. These derivatives also showed inhibitory activity to 5-LO with their IC50 values ranged from 6.1 +/- 0.1 mu M to 35.9 +/- 0.3 mu M. 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. (C) 2013 Elsevier Masson SAS. All rights reserved.