L-Tryptophan Schiff Base Cadmium(Ii) Complexes As A New Class of Proteasome Inhibitors and Apoptosis Inducers in Human Breast Cancer Cells

Although cadmium is a widespread environmental contaminant and human carcinogen, our studies indicate an organic cadmium complex to be a potent inhibitor of proteasomal chymotrypsin-like (CT-like) activity, further capable of inducing apoptosis in a cancer cell-specific manner. Many clinical studies suggest the use of proteasome inhibitors as potential novel anticancer agents and in the present study, we have synthesized three novel l-tryptophan-containing cadmium complexes: Cd(C17H15N4O2)2·2CH3OH (1) (C17H15N4O2=2-acetylpyrazine-l-tryptophan), Cd(C17H15N2O3)2·2CH3OH (2) (C17H15N2O3=5-methylfurfural-l-tryptophan) and Cd(C16H12N2O2SBr)2·2CH3OH (3) (C16H12N2O2SBr=5-bromo-2-thiophenecarbaldehyde-l-tryptophan) and found that under comparable conditions cadmium complexes 1 and 2, but not 3, have proteasome-inhibitory activity in human breast cancer MDA-MB-231 cells. Our results suggest that l-tryptophan Schiff base cadmium complexes are potent proteasome inhibitors.