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.
Keywords: 1-ethyl-3-(3-dimethylaminoprpyl) carbodiide; 5-LO; 5-Lipoxygenase; 5-lipoxygenase; 5-lipoxygenase activating protein; AD; ADAM10; APP; Alzheimer's disease; Amyloid-beta aggregation; Anti-Alzheimer agent; Aβ; BACE1; CD; CNS; CREB; EDC; EM; FLAP; HOBt; ISL; Inhibitors; Isoliquiritigenin derivatives; MTT; N-hydroxybenzotriazole; NDGA; Resv; SAR; a disintegrin and metalloproteinase domain-containing protein 10; amyloid beta protein; amyloid precursor protein; beta-site APP cleaving enzyme 1; cAMP-response element binding protein; central nervous system; circular dichroism; electron microscopy; isoliquiritigenin; methyl thiazolyl tetrazolium; nordihydro-guaiaretic acid; resveratrol; structure–activity relationships.
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