Protective effects of 1,3-diaryl-2-propen-1-one derivatives against H₂O₂-induced damage in SK-N-MC cells

Alzheimer's disease (AD) is an age-related neurodegenerative disorder of the central nervous system resulting in memory loss and dementia. Some of the associated pathogenic changes are amyloid peptide aggregation, excitotoxicity, oxidative stress and inflammation. Oxidative stress plays an indispensable role in the pathophysiology of AD. Therefore, antioxidant therapies appear to be promising approaches in dealing with AD patients. In that line, we evaluated the free radical scavenging capabilities of 13 different chalcones (1,3-diphenyl-2-propen-1-one) derivatives against the free-radical damaging effects of hydrogen peroxide (H₂O₂) on the SK-N-MC neuroblastoma cell line. Pretreatment of the cells for 3h with 20μ m of each of these derivatives (compounds 8-20) followed by exposure to 300μ m H₂O₂ for 24h indicated that all compounds, except compound 20, were capable of restoring the viabilities of cells relative to the control (H₂O₂-treated) cells. The destructive effect of H₂O₂ on the adhesive behavior of the cells was almost totally restored by each of the derivatives. In addition, each of the derivatives except compounds 20 and 14 significantly reduced the extent of lipofuscin formation among the cells time-dependently. Despite these activities, some of the derivatives, such as compounds 12 and 19, did not reduce the H₂O₂-induced intracellular ROS (reactive oxygen species) levels, meaning that these two derivatives act through a different mechanism other than free-radical scavenging activity. On the other hand, for those derivatives acting as anti-oxidants, structure-activity evaluation clearly revealed that the hydroxyl group of vanillin ring is required for their free-radical scavenging activities.