Synthesis and biological evaluation of β-ionone oriented proapoptosis agents by enhancing the ROS generation

β-ionone, a cyclic terpenoid compound present in many fruits, has been showed a broad spectrum of biological activities. In this paper, we synthesized a panel of β-ionone derivatives and tested their anti-proliferation activity on cancer cell by the MTT assay. The results showed that most of the β-ionone derivatives were more active than β-ionone and curcumin. Particularly, the β-ionone derivatives (1a, 1d and 1g) with ortho-substituents on the aromatic ring exhibited much stronger cytotoxicity than their corresponding meta- and para-substituted compounds. Importantly, the cytotoxicity of the β-ionone derivatives (1a, 1d and 1g) were relationship with their reactive oxygen species (ROS)-generation abilities, which could lead to the redox imbalance, lipid peroxidation, the loss of mitochondrial membrane potential (MMP), the activation of Bax and Caspase 3, followed by cell apoptosis. This work suggest that the “ortho effect”, the ROS-generation ability and drawing fluorine atom into drugs may play a potent role in enhancing the anticancer activity of β-ionone derivatives.