Amyloid Β-peptide (AΒ-peptide)-induced oxidative stress is thought to be a critical component of the pathophysiology of Alzheimer's disease (AD). New chalcone derivatives, the Chana series, were recently synthesized from the retrochalcones of licorice. In this study, we investigated the protective effects of the Chana series against neurodegenerative changes in vitro and in vivo. Among the Chana series, Chana 30 showed the highest free radical scavenging activity (90.7%) in the 1,1-diphenyl-2- picrylhydrazyl assay. Chana 30 also protected against AΒ-induced neural cell injury in vitro. Furthermore, Chana 30 reduced the learning and memory deficits of AΒ(1-42)-peptide injected mice. Taken together, these results suggest that Chana 30 may be a promising candidate as a potent therapeutic agent against neurodegenerative diseases. [BMB reports 2011; 44(11): 730-734].