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Potent Anticancer Efficacy of First‐In‐Class Cu II and Au III Metaled Phosphorus Dendrons with Distinct Cell Death Pathways
Author(s) -
Chen Liang,
Fan Yu,
Qiu Jieru,
Laurent Régis,
Li Jin,
Big Jérôme,
Mignani Serge,
Caminade AnneMarie,
Shi Xiangyang,
Majoral JeanPierre
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202001014
Subject(s) - cytotoxicity , apoptosis , programmed cell death , chemistry , cytochrome c , stereochemistry , alkyl , cell , caspase , biochemistry , in vitro , organic chemistry
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).