Synthesis and anti-metastatic effects of novel chiral ionone alkaloid derivatives

Novel chiral ionone alkaloid derivatives were synthesized and evaluated their anti-metastatic effects in human MDA-MB-231 breast cancer cells. The chiral center C-6 of derivatives exerted an important role in response to the anti-metastatic activity. Comparing with a positive control of LY294002, compounds 17b and 19a exhibited potent inhibitory effects on the EGF-induced invasion of MDA-MB-231 cells with IC50 values of 0.026 ± 0.003 and 0.016 ± 0.002 μM, respectively. Moreover, compounds 17b and 19a showed inhibitory effects on the expressions of p-PKCζ and p-integrin β1 in MDA-MB-231 cells in a dose-dependent manner. Thus, compounds 17b and 19a offer potential to be developed as novel anti-metastasis agents.