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Breast cancer stem cells (CSCs) are a sub-population of tumour cells that can promote breast cancer relapse and metastasis. Current treatments are unable to completely remove breast CSCs, therefore it is essential to develop new chemotherapeutics that can remove breast CSCs at clinically compatible doses. Here we present the synthesis, characterisation, and anti-breast CSC properties of copper(II) complexes, [Cu(L2)(1,10-phenanthroline)]PF6 (2) and [Cu(L3)(1,10-phenanthroline)]PF6 (3) comprising of a tridentate (O,N,S) coordinated naphthol Schiff base ligand (L2 = (E)-1-(((2-(methylthio)ethyl)imino)methyl)naphthalen-2-ol or L3 = (E)-1-(((2-(ethylthio)ethyl)imino)methyl)naphthalen-2-ol and 1,10-phenanthroline. The copper(II) complexes (2 and 3) kill breast CSCs, cultured in monolayer and three-dimensional systems, in the micromolar range. Notably, 2 and 3 are more potent towards breast CSC mammospheres than salinomycin (up to 4.5-fold), an established anti-breast CSC agent. Further, cell-based studies indicate that 2 and 3 are readily taken up by breast CSCs and elevate intracellular reactive oxygen species (ROS) levels upon short exposure times (0.5–1 h). The latter is likely to be the underlying mechanism by which 2 and 3 induces breast CSC death.

Breast Cancer Stem Cell Active Copper(II) Complexes with Naphthol Schiff Base and Polypyridyl Ligands