9.
First-in-class Cu
II and Au
III metaled phosphorus dendrons were synthesized and showed significant antiproliferative activity against several aggressive breast cancer cell lines. The data suggest that the cytotoxicity increases with reducing length of the alkyl chains, whereas the replacement of Cu
II with Au
III considerably increases the antiproliferative activity of metaled phosphorus dendrons. Very interestingly, we found that the cell death pathway is related to the nature of the metal complexed by the plain dendrons. Cu
II metaled dendrons showed a potent caspase-independent cell death pathway, whereas Au
III metaled dendrons displayed a caspase-dependent apoptotic pathway. The complexation of plain dendrons with Au
III increased the cellular lethality versus dendrons with Cu
II and promoted the translocation of Bax into the mitochondria and the release of Cytochrome C (Cyto C).
相似文献