Cinnamic acid/β-ionone hybrids: synthesis and in vitro anticancer activity evaluation

The hybrid approach, encompassing two pharmacophores in one molecular scaffold, has attracted much attention in medicinal chemistry. In this study, we synthesized a panel of hybrid molecules based on the natural active ingredients, beta-ionone and 3,4,5-trimethoxycinnamic acid. The results exhibited that 3,4,5-trimethoxy-hybrid displayed the most excellent cytotoxicity against cancer cells, whereas, the electron effect of substituents plays no distinct effect on antiproliferative activity. The cytotoxicity of 3,4,5-trimethoxy-hybrid may be due to its cell cycle arrest and apoptosis-inducing activities, which may be relationship with the reactive oxygen species generation, redox imbalance, lipid peroxidation and the collapse of mitochondrial membrane potential induced by 3,4,5-trimethoxy-hybrid in A549 (human lung adenocarcinoma) cells. In conclusion, 3,4,5-trimethoxy-hybrid could induce cancer cell apoptosis through the reactive oxygen species generation. [GRAPHICS] .