3,5-Bis(2-Trifluomethoxybenzylidene)-4-Piperidone Induces Apoptosis in A549 Cells Through Reactive Oxygen Species-Mediated Pathways

Abstract

Medicines with the F₃C-O group can increase the lipophilicity of an aromatic ring system and protect it from oxidative attacks. We have synthesized 3,5-bis(2-trifluomethoxybenzylidene)-4-piperidone (4a), an EF24 analog with ortho trifluoromethoxy group, via aldol condensation reaction and evaluated its cytotoxicity by MTT assay. Owning to the ortho-trifluoromethoxy group, compound 4a exhibited excellent cytotoxicity against A549 cells. Mechanistic investigation indicated that 4a could induce oxidative stress, including the generation of reactive oxygen species (ROS), imbalance of redox buffering system, lipid peroxidation, and collapse of mitochondrial membrane potential, and finally leading to cell apoptosis. These data indicated that the introduction of the ortho-trifluoromethoxy group into curcumin analogs may be an effective strategy to enhance the anti-cancer ROS based activity.